• The Korean Journal of Physiology and Pharmacology
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• v.15 no.5
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• pp.273-277
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• 2011

Nitric oxide (NO) and atrial natriuretic peptide (ANP) may induce vascular relaxation by increasing the production of cyclic guanosine monophosphate (cGMP), an important mediator of vascular tone during sepsis. This study aimed to determine whether regulation of NO and the ANP system is altered in lipopolysaccharide (LPS)-induced kidney injury. LPS (10 $mg{\cdot}kg^{-1}$) was injected in the tail veins of male Sprague-Dawley rats; 12 hours later, the kidneys were removed. Protein expression of NO synthase (NOS) and neutral endopeptidase (NEP) was determined by semiquantitative immuno-blotting. As an index of synthesis of NO, its stable metabolites (nitrite/nitrate, NOx) were measured using colorimetric assays. mRNA expression of the ANP system was determined by real-time polymerase chain reaction. To determine the activity of guanylyl cyclase (GC), the amount of cGMP generated in response to sodium nitroprusside (SNP) and ANP was calculated. Creatinine clearance decreased and fractional excretion of sodium increased in LPS-treated rats compared with the controls. Inducible NOS protein expression increased in LPS-treated rats, while that of endothelial NOS, neuronal NOS, and NEP remained unchanged. Additionally, urinary and plasma NOx levels increased in LPS-treated rats. SNP-stimulated GC activity remained unchanged in the glomerulus and papilla in the LPS-treated rats. mRNA expression of natriuretic peptide receptor (NPR)-C decreased in LPS-treated rats, while that of ANP and NPR-A did not change. ANP-stimulated GC activity reduced in the glomerulus and papilla. In conclusion, enhancement of the NO/cGMP pathway and decrease in ANP clearance were found play a role in the pathogenesis of LPS-induced kidney injury.

• Childhood Kidney Diseases
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• v.5 no.2
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• pp.164-175
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• 2001

Purpose : Alport syndrome is a hereditary nephrotic disease characterized by progressive nephrotic symptom, sensorineural hearing loss, ophthalmic abnormality, typical microscopic findings, and familial occurrence. In this study, we tried to find the risk factors related with its prognosis by taking a close observation on clinical symptoms of children with Alport syndrome reviewing retrospectively. Materials & methods : We chose children diagnosed as Alport syndrome in renal biopsy during 20 years(from 1980, Jan. until 1999, Dec.) who could receive follow up studies in tile department of pediatrics. They were divided into two groups by comparing renal function at the time of diagnosis and at current status. We compared several clinical aspects in them, and applied nonparametric test for statistical analysis. Results : The sex ratio(male:female) of 24 children was 3:1. The most common clinical symptom presented at their first visit was gross hematuria. Among those 24 children, 11 cases($46\%$) of progressing into chronic renal failure(Group II) were observed. Hypertension, proteinuria and edema were seen much frequently in group II. The level of serum protein, albumin, and creatinine clearance were decreased while BUN, creatinine were relatively increased. All the results were statistically significant. Conclusion Clinically significant risk factors related to prognosis in Alport syndrome were the presence of hypertension, edema, and proteinuria at the time of diagnosis. Also, the level of serum protein, albumin, BUN, creatinine, and glomerular filtration rate were proved to be important factors in predicting prognosis. We believe that studies on these possible risk factors would be of great help in treating and predicting prognosis of children suffering with Alport syndrome. (J Korean Soc Pediatr Nephrol 2001;5 : 164-75)

• Journal of Nutrition and Health
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• v.29 no.5
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• pp.461-471
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• 1996

This study was performed to investigate the effect of dietary protein and cysteine levels on cadmium toxicity in rats. Seventy-two male rats of Sprague-Dawley strain weighting 171$\pm$3g were blocked into 12 groups according to body weight, and were raised for 30 days. cadmium chloride was given at levels of 0 or 400ppm, protein at levels of 7, 15 and 40%, and cysteine was added(total dietary cysteine contents : 0.45%) to diet or not. The results are summarized as follow. Food intake, weight gain, food were lower than those of cadmium free group. But, these were increased with increasing dietary protein level and cysteine addition. Fecal cadmium excretion was remarkably increased in high protein (40%) groups. Thus, cadmium retention rates were decreased in high protein groups. Metallothionein concentrations in liver and kidney were increased in cysteine addition, and cadmium administration. Especially, these were remarkably increased in cadmium and cysteine added groups. Urinary calcium excretion was increased with cadmium administration, but urinary protein excretion and creatinine clearance were not changed in these animal. In conclusion, food intake, weight gain and organ weights were decreased with administration. Cadmium toxicity was alleviated by increasing fecal cadmium excretion, while cysteine addition increased metallothionein concentrations in liver and kidney. From these results, it was shown that cadmium toxicity was alliviated by synergistic effect of high protein level and cysteine addition.

• Journal of Pharmaceutical Investigation
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• v.20 no.1
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• pp.19-28
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• 1990

Pharmacokinetic parameters of aminoglycosides are dependent on renal function, sex, age, hematocrit, fever, lean body weight (LBW) and disease states, etc. Therefore, the individual pharmacokinetic parameters such as half life $(t^{1/2})$ and volume of distribution(Vd) are needed to achieve optimal therapy. However these parameters had not been determined in Koreans. The purpose of this study was to evaluate the Vd and $t^{1/2}$ of amikacin in Korean patients who had normal renal function, to compare the mean values of study group with that reported in the literature and to compare the measured $t^{1/2}$ with the expected $t^{1/2}$ based on actual body weight (ABW), LBW and ideal body weight (IBW), respectively. Based on data, the Vd was greater than the literature and $t^{1/2}$ was similar to the literature. The predicted $t^{1/2}$ based on IBW was the closest to actual $t^{1/2}$. And postpartum patients had greater Vd than other group and had lower correlation between actual elimination rate constant and calculated creatinine clearance but higher correlation between actual elimination rate constant and Vd than other group.

• YAKHAK HOEJI
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• v.46 no.1
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• pp.63-68
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• 2002

The purpose of this study was to estimate the population pharmacokinetics of clarithromycin in healthy adult Korean and to investigate the factors influencing the pharmacokinetics of clarithromycin. The population pharmacokinetic parameters of clarithromycin were calculated with the data from healthy adult Koreans. A total of 798 plasma concentrations obtained from 78 subjects after administration of a single oral dose of 250 mg or 500 mg were used for the modeling. The concentration-time data were fitted to a one-compartment open model assuming a first-order absorption and elimination with no lag time. The correlations between various factors [such as sex, age, height, weight, sect creatinine (Scr) and dose and pharmacokinetic parameters were estimated with stepwise linear recession analyses. The selected covariates were incorporated in the population model of NONMEM, and the importance of each covariate was investigated by means of backwards elimination. The apparent clearance (CL/F) was significantly correlated to Scr and sex, and the apparent volume of distribution (Vd/F) was significantly correlated to Scr and height in a nonlinear relationship. The population values of Ka was 1.8 h $r_{-1}$, CL/F was 37.71 L/hr, Vd/F was 200 L and t/ sub 1/2 / was 3.68 hrs for a male Korean with 170 m height and 1.0 mg/dL Scr.

• Asian-Australasian Journal of Animal Sciences
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• v.5 no.1
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• pp.81-90
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• 1992

Five buffaloes kept in normal ambient temperature ($30^{\circ}C$) showed no significant changes in the heart rate, respiratory rate, packed cell volume, plasma constituents and renal hemodymics during intravenous infusion of urea for 4 h. The rate of urine flow, fractional urea excretion, urinary potassium excretion and osmolar clearance significantly decreased while the renal urea reabsorption markedly increased during urea infusion. The decrease of fractional potassium excretion was concomitant with the reduction of the rate of urine flow and urine pH. In animals exposed to heat ($40^{\circ}C$) the rectal temperature heart rate and respiratory rate significantly increased while no significant changes in GFR and ERPF were observed. An intravenous infusion of urea in heat exposed animals caused the reduction of the rate of urine flow with no changes in renal urea reabsorption, urine pH and fractional electrolyte excretions. During heat exposure, there were marked increases in concentrations of total plasma protein and plasma creatinine whereas plasma inorganic phosphorus concentration significantly decreased. It is concluded that an increase in renal urea reabsorption during urea infusion in buffaloes kept in normal ambient temperature depends on the rate of urine flow which affect by an osmotic diuretic effect of electrolytes. The limitation of renal urea reabsorption in heat stressed animals would be attributed to an increases in either plasma pool size of nitrogenous substance or body metabolism.

• Herbal Formula Science
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• v.16 no.2
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• pp.163-169
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• 2008

The kidney toxicities of BDR-29 used for improvement of the vascular diseases, was examined using male and female Sprague-Dawley rats. The male and female rats were divided into 4 groups for intragastrical treatment with doses of 0, 5, 50, and 500 mg/kg/day for 13 weeks, respectively. In all male and female rats treated with BDR-29, no mortality and gross pathological findings were shown for 13 weeks. There substantially was no change in body weight in all rats with treatment of BDR-29. The renal functional parameters including urinary volume, urine osmolality, electrolytes excretory rate, creatinine clearance, and solute-free water reabsorption were not exchanged in all rats treated with BDR-29. Taken together, these results suggest that BDR-29 has no toxicity on kidney in all male and female rats.

• Childhood Kidney Diseases
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• v.1 no.2
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• pp.183-188
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• 1997

Familial juvenile hyperuricemic nephropathy is an autosomal dominant disease characterized by progressive renal disease and hyperuricemia or gout, affecting young people of either sex equally. There are two biochemical markers of this disorder. The first is hyperuricemia disproportionate to the degree of renal dysfunction; the second is a grossly reduced clearance of uric acid relative to creatinine, dispropotionate to age, sex and degree of renal failure. We experienced 2 family members with hyperuricemia. One family member, a 13-year-old girl who had suffered from tophaceous gout and chronic renal failure. Her younger brother also had hyperuricemia and moderately reduced renal function. Their urinary excretion fractions of uric acid($FE_{uric\;acid}$) were reduced and renal biopsy specimens showed interstitial fibrosis with tubular atrophy and interstitial urate crystal deposition. We have treated these two patients with allopurinol but we have done renal transplantation because she progressed to end stage renal disease at 16 year old age.

• Journal of Pharmaceutical Investigation
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• v.3 no.4
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• pp.28-38
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• 1973

The mechanism of urinary excretion of sulfadiazine was investigated in the dogs by means of stop-flow technique Results of experiments were summarized as follows; 1. The ratios of U/P sulfadiazine to U/P creatinine $(U/P_{SD}:U/P_{cr})$ were always lower than 1 in all nephrons, showed a minimum in the proximal area. 2. $U/P_{SD}:U/P_{cr}$ were not affected by Probenecid or 2.4-DNP, whereas increased significantly by administration of sodium bicarbonate. 3. Probenecid did not alter the stop-flow patterns in alkalotic dog too. 4. $C_{SD}$ (clearance of sulfadiazine ) was appreciably influenced by change in urinary PH, or flow rate. All evidences lead to the conclusion that sulfadiazine reabsorption is passively transported by proximal tubules. No clue for active process, either secretory or reabsorptive, was obtained.

• Korean Journal of Clinical Pharmacy
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• v.3 no.1
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• pp.15-20
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• 1993

The ability to precisely predict serum digoxin concentration using 7 published methods in a group of 50 patients was undertaken. Two methods of estimating creatinine clearance and two estimates of lean body weight were employed as input variables using the 7 dosing methods. TDX was used to determine the nadir SDCs(serum digoxin concentrations) in 50 in patients meeting predetermined study criteria. All patients, whose ages ranged 19-71 years, had steady-state digoxin levels, were in oral digoxin, and were free from liver dysfunction, thyroid dysfunction and renal failure. The correlation coefficients(r) of predicted versus observed SDCs were determined,. and mean error(ME) was determined for each method to reflect bias, respectively. No substantial differance in predictive reliabliity was evident among the methods studied in total group. Poor correlations existed between predicted and observed SDCs(r<0.4) and these correlations were not significantly affected by age and gender. But relatively higher correlation and lower ME was founded for the CHF group in Jelliffe method(r=0.5, p<0.05).