• The Korean Journal of Physiology and Pharmacology
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• 제15권5호
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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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• 제5권2호
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• pp.164-175
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• 2001

목 적 ; Alport 증후군은 1927년 Alport에 의해 처음 보고된 유전성 신질환으로 전신적으로 기저막에 영향을 미쳐 계속적으로 진행하는 신질환과 감각신경성 난청, 눈의 이상, 전자현미경상 특징적 소견, 그리고 대부분의 경우 가족력 동반을 특징으로 한다. 저자들은 Alport 증후군 환아의 임상적 특징을 중심으로 관찰하여 이 질환의 예후에 관련된 위험요인을 알아보고자 후향적 조사를 시행하였다. 대상 및 방법 : 1980년 1월부터 1999년 12월까지 20년동안 소아과에서 시행한 신장조직검사에서 Alport 증후군으로 진단 후 추적관찰이 가능하였던 환아 24명을 대상으로 하였다. 처음 내원 당시와 현재의 신장기능을 비교하여 현재까지 정상의 신장기능을 유지하고 있는 군(Group I)과 만성신부전으로 진행한 군(Group II)으로 나누어 Group I과 Group II간의 여러 가지 임상양상을 비교하였으며 통계학적 방법으로는 비모수검정법을 이용하였다. 결 과 : 24명의 환아 중 남녀의 비는 3:1이였고 신증상 발현시의 연령은 평균 $5.2{\pm}3.6세$였으며 내원 당시 나이는 평균 $7.8{\pm}4.4세$였다. 처음 내원 당시의 주증상은 육안적 혈뇨가 15예($62\%$)로 가장 많았고, 진단 당시의 환아들의 임상양상으로는 가족력이 있는 경우가 17예($70\%$), 육안적 혈뇨는 18예($75\%$), 단백뇨가 있었던 경우가 14예($58\%$), 부종은 14예($58\%$), 고혈압은 6예($25\%$)에서 관찰되었다. 전체 24명의 환아 중 만성신부전으로 진행된 경우는 11예($46\%$)였고, 이 중 말기신부전으로 진행되어 신장이식 후 관찰 중인 경우가 7예($29\%$) 있었다. 청각이상소견을 보인 경우는 12예($50\%$)였으며, 안과적 정밀검사상 이상소견을 보인 경우는 5예($21\%$)였다. 신증상 발현이후 계속해서 신장기능이 유지되고 있는 집단을 Group I(n=13), 만성신부전으로 진행한 집단을 Group II(n=11)라고 할 때, 이 두 집단 사이의 진단당시의 임상양상의 차이를 보면 고혈압, 단백뇨 및 부종의 빈도가 Group I에서 통계적으로 유의하게 증가되어 있으며, 임상병리검사 소견에서는 혈중 총단백량, 알부민, creatinine 청소율이 Group I에서 통계적으로 유의하게 감소되어 있고, BUN, creatinine은 통계적으로 유의하게 증가되었다. 결 론 : Alport 증후군 환아에서 임상적으로 유의미한 예후와 관련된 위험요인으로는 진단시의 고혈압, 부종, 단백뇨 유무 여부와 혈중 총단백량, 알부민, BUN, creatinine, 사구체 여과율이 중요하며, 이런 가능한 위험요인의 분석과 관찰이 Alport 증후군 환아의 치료와 예후 인지에 많은 도움이 되리라 사료된다.

• Journal of Nutrition and Health
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• 제29권5호
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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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• 제20권1호
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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.

• 약학회지
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• 제46권1호
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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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• 제5권1호
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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.

• 대한한의학방제학회지
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• 제16권2호
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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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• 제1권2호
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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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• 제3권4호
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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.

• 한국임상약학회지
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• 제3권1호
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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).