• The Korean Journal of Pharmacology
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• v.22 no.2
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• pp.79-87
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• 1986

Recently it has been shown that central dopaminergic system regulates the renal function and that intracerebroventricularly (icv) administered dopamine (DA) produces antidiuresis and antinaturiuresis, resembling icv norepinephrine, and evidence has been accumulated which would suggest the involvement of adrenergic system in the DA effects. It was attempted therefore in this study to see whether the DA effect is influenced by pretreatment of yohimbine which is known as a specific ${\alpha}_2-adrenoceptor$ antagonist. Yohimbine produced, when given icv in doses of $100\;{\mu}g/kg$, marked antidiuresis and antinatriuresis along with decreases in renal perfusion and glomerular filtration. DA, in doses of $15\;{\mu}g/kg$, also produced antidiuresis and antinaturiuresis. However, after yohimbine-pretreatment DA $15\;{\mu}g/kg$ improved renal hemodynamics, and electrolyte excretion and urine flow rate transiently increased. With $150\;{\mu}g/kg$ DA, the antidiuresis was more marked in the control group. But the yohimbine-pretreated animals responded with marked diuresis and natriuresis, sodium excretion increasing more than three-fold, which lasted for 20 minutes. $K^+-excretion$, osmolar clearance as well as free-water reabsorption increased. Renal hemodynamics improved partly. Apomorphine, a DA agonist, when given icv in doses of $150\;{\mu}g/kg$, produced diuresis and naturiuresis, concomitant with increased renal hemodynamics. Yohimbine-pretreatment however did not abolish the apomorphine-induced diuresis and naturiuresis. Antidiuresis and antinatriuresis elicited by norepinephrine, $10\;{\mu}g/kg$, was not affected by yohimbine-pretreatment. These results indicate that the renal effects of icv DA is not so simple as those of norepinephrine, and the diuretic natriuretic cffect which had been masked by the hemodynamic effect becomes manifest only when the decreases in hemodynamics were removed by the pretreatment of yohimbine. It was further suggested that those DA receptors which mediate the natriuretic response to icv DA is not affected by yohimbine, whereas those receptors involved in the decrease in renal hemodvnamics are blocked by yohimbine. And the possibility of involvement of adrcnergic system in the DA action is not substantiated.

• The Korean Journal of Nuclear Medicine
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• v.33 no.4
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• pp.398-404
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• 1999

Purpose: Diabetic nephropathy is the most common cause of end stage renal disease and the incidence is progressively increasing. The aim of this study was to investigate the differences of $^{99m}Tc$-DMSA renal uptake among diabetic patients with normoalbuminuria, microalbuminuria and overt proteinuria, and then to determine the clinical usefulness of $^{99m}Tc$-DMSA in predicting early diabetic nephropathy Materials and Methods: $^{99m}Tc$-DMSA scan was performed and a total renal uptake of $^{99m}Tc$-DMSA was measured in 145 diabetic patients. Patients were divided into 3 groups according to the amount of 24 hour urinary albumin excretion as Group I (normoalbuminuria, 74 cases), Group II (microalbuminuria, 39 cases), and Group III (overt proteinuria, 32 cases). The differences of $^{99m}Tc$-DMSA renal uptake among the 3 groups and the correlation between the renal uptake of $^{99m}Tc$-DMSA and other clinical parameters were analyzed. Results: The total renal uptake of $^{99m}Tc$-DMSA of Group II ($40.8{\pm}11.0%$) was significantly lower than that of Group I ($54.4{\pm}6.3%$, p<0.001). The uptake of Group III ($27.7{\pm}12.0%$) was significantly lower than those of both Group I and Group II (p<0.001). $^{99m}Tc$-DMSA total renal uptakes correlated negatively with serum creatinine level (r=-0.629, p<0.001) and positively correlated with creatinine clearance rate (r=0.102, p<0.001). Conclusion: $^{99m}Tc$-DMSA total renal uptake of diabetic patients with microalbuminuria was significantly decreased compared with that of patients of normoalbuminuria. Therefore, $^{99m}Tc$-DMSA scan can be used as a diagnostic study for early detection of the diabetic nephropathy.

• Tuberculosis and Respiratory Diseases
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• v.45 no.2
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• pp.360-368
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• 1998

Background: Endothelin(ET), a potent vasoconstrictor peptide produced by endothelial cells and degraded predominantly in the pulmonary vasculature, have been implicated in the development of various organ dysfunctions. Plasma concentrations of ET-1 are reported to be elevated in patients with diffuse interstitial lung disease(DILD). But, there is no study to establish the exact source and mechanisms involved in the increased plasma ET-1 concentrations in DILD patients. Methods: 12 patients with IPF, 2 patients with sarcoidosis, 2 patients with scleroderma, 1 patient with SLE and 11 healthy volunteers were studied. ET was detected by radioimmunoassay in plasma and bronchoalveolar lavage fluid(BALF) as well as in 24-hr urine specimens. For each subjects, arterial/venous(A/V) ET ratio and renal ET clearance were calculated. Results: Elevated plasma, urine and BALF ET concentrations were found in patients with DILD compared with controls. But, no significant difference was observed in ET A/V ratio and ET renal clearance between patients with DILD and controls. Conclusion: We observed that plasma ET concentrations were elevated in patients with DILD, and that the main site of ET production may be lung parenchyme.

• Journal of Yeungnam Medical Science
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• v.3 no.1
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• pp.229-235
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• 1986

Lithium salts are being used increasingly to treat patient with affective disorders, especially acute mania, or bipolar manic-depressive illness. For therapeutic effect the lithium content must be maintained at or above a particular level. Lithium poisoning due to overdosage may be seen occasionally, and its course is determined primarily by the rate of renal lithium elimination. A search is therefore indicated for procedures that could raise the lithium clearance. In a number of reports renal lithium excretion has been studied in relation to the excretion of water, sodium, potassium and hydrogen, but effects of sodium or water on the lithium excretion has not yet been clarified. Hence the present study was undertaken to investigate the effects of corticosteroid on the excretion of lithium ion. The female rat(Sprague-Dowley), weighing from 200 to 300g, was injected with 50mg/kg of lithium chloride intraperitoneally, and then injected with graded dosage of fludrocortisone and dexamethasone in each group. During the injected rats were incubated in metabolic cage, 24 hour urine of rats were collected. At 24 hours after injection, the rats were sacrificed with guillotin, the blood were collected. And then the concentratios of $Na^+$, $K^+$, $Li^+$ of collected urine and serum were checked by Flame photometer. The results are summarized as follows; 1. Fludrocortisone decreased the serum concentration of lithium and increased the urinary excretion of lithium. 2. In the group treated with low dose of dexamethasone(0.1mg/kg), the serum concentration of lithium was decreased and high dose of dexamethasone (1mg/kg) increased the urinary excretion of lithium. 3. Fludrocortisone increased the urinary $[Na^+]/[K^+]$ in serum and decreased $[Na^+]/[K^+]$ in urine, but opposite effects were occurred in dexamethasone. By above results, it may be concluded that corticosteroid increased the urinary excretion of lithium and decreased the serum concentration of lithium, but it seems to be there is no relationship between these effects of corticosteroid and of the renal $Na^+$ or $K^+$ transport.

• Journal of Veterinary Clinics
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• v.29 no.2
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• pp.130-133
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• 2012

The purpose of this study is to assess the relationship between glomerular filtration rate (GFR) and age by using dynamic computed tomography (CT) and Patlak plot analysis in dogs. Fifteen dogs were used in this study. CT-GFR study was performed under general anesthesia using propofol and isoflurane. 1 ml/kg dosage of 300 mgI/ml iohexol was administered at a rate of 3 ml/s during GFR measurement. CT-GFR was determined with a single-slice dynamic acquisition and Patlak plot analysis. The individual and global GFR values were calculated to plasma clearance per body weight (ml/min/kg). Bodyweight ($mean{\pm}SD$) ranged from 2.0 to 5.7 kg ($3.31{\pm}1.13$ kg). Age ranged from 3 years to 13 years old ($7.14{\pm}3.30$). $Mean{\pm}SD$ creatinine ($0.53{\pm}0.34 $mg/dl), phosphorus ($4.1{\pm}1.2$ mg/dL), and albumin ($3.3{\pm}0.3$ mg/dL) concentrations and urine protein-to-creatinine ratios (all ratios were < 0.5) were within reference ranges. Abdominal ultrasonography revealed small-sized renal calculi, mineralization, or renal cyst at eight dogs. The global CT-GFR ranges shown in this study was 2.57 to 6.60 ml/min/kg. In this study, there was no trend toward weight-adjusted CT-GFR with increasing age. We found no relationships between age-related kidney dysfunction in fifteen dogs. Small-sized renal calculi or cysts did not affect renal function in this study. However, it is thought that a large sample size may have been required to document an age effect.

• Journal of Pharmaceutical Investigation
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• v.34 no.3
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• pp.161-168
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• 2004

5-Fluorouracil (5-FU) is an antimetabolite anticancer agent active against many types of solid tumors. Tegafur (TF), a prodrug of 5-FU, is frequently used in combination with uracil as dihydropyrimidine dehydrogenase (DPD) inhibitory fluoropyrimidine. We studied the stability of 5-FU and TF in biological fluids of rats and determined their bioavailability (BA) and excretion into bile, and urine. The drug concentrations were analyzed by an HPLC method. At room temperature, there was a 14-30% decrease in the concentration of 5-FU and TF in bile, urine, and plasma specimen at 10 and $100\;{\mu}g/ml$ over 240 min. No significant difference was noted among the sample types or between two different concentrations of 10 and $100{\mu}g/ml$. The decrease in drug concentration was significantly less in samples kept on ice (6-12%) for both drugs. These data indicate that biological fluid samples containing 5-FU or TF in plasma, urine, or bile should be placed on ice during the sample collection. Following these storage guidelines, samples were collected after administration 50 mg/kg of each drug via i.v. or oral route. BA was 1.5 folds greater for TF (60%) than that of 5-FU (42%). Approximately 0.52 and 3.3% of the i.v. doses of 5-FU and TF was excreted into bile, respectively. Renal clearance of 5-FU was about 16% of its total body clearance. These results suggest that instability of 5-FU and TF in biological fluids should be considered in pharmacokinetic or pharmacogenomic studies.

• 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.

• The Korean Journal of Physiology
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• v.25 no.2
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• pp.189-200
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• 1991

During the past few years it has been proposed that lithium clearance can be used as a reliable measure for the outflow of tubular fluid from the proximal tubule. This study was aimed to characterize the inflow dependent reabsorption of Na in renal tubule beyond the proximal tubule. For this purpose, lithium clearance was used as a measure for the inflow from the proximal tubule and the changes in reabsorption fraction of Na and water were determined in rabbits. Rabbits were pretreated with hypotonic saline solutions for an hour (50 mM/L NaCl, 20 ml/hr/kg). And then a hypertonic solution of 500 mM/L NaCl (20 ml/kg) was administered intraperitoneally in conjunction with a bolus of LiCl solution (2 mM/kg, i.v.) for conditioning the $C_{Li}$ and urine flow rate. To rule out the effect of $Li^+$ on tubular functions, a bolus of NaCl solution (2 mM/kg, i.v.) was administered. Fifteen, thirty, and sixty minutes after injection of hypertonic saline arterial blood and urine samples were taken. Urinary and plasma concentrations as well as urinary output of $Li^+,\;Na^+\;and\;K^+$ were measured. From these $C_{Li},\;C_{Na}$ and the reabsorption fraction of Na and water $(Fr_{Na}\;&\;FrH_2O)$ were calculated. These results were compared with those from control groups in which the same amount of isotonic saline (145 mM/L NaCl) and of 15% dextran solution were administered in the same way as that in experimental group. Followings are the results obtained. 1) The plasma concentration of $Na^+$ in rabbits injected with hypertonic saline reached the peak value after 15 min and thereafter no significant change was observed. Hematocrit values did not show any change, while urinary excretion of $Na^+$ increased markedly during the first 15 min and decreased thereafter. These results were not affected by an injection of a small amount of LiCl. 2) The clearances of $Li^+,\;Na^+\;and\;K^+$ in rabbits injected with hypertonic saline and LiCl solution decreased. 3) In spite of the variation in $C_{Li},\;Fr_{Na}$ did not show any significant change while $FrH_2O$ increased gradually. 4) $C_{Li}$ decreased also in rabbits received isotonic saline. $Fr_{Na}$ tended to be higher than that in hypertonic saline group, while $FrH_2O\;and\;Fr_{Na}$ did not associated with the decrease in $C_{Li}$. 5) $C_{Li}$ of the rabbits received dextran solution fluctuated persistently and $Fr_{Na}\;and\;FrH_2O$ did not change in along with $C_{Li}$ although $Fr_{Na}$ had a tendency to be higher than that in hypertonic saline group. 6) From the above results it was concluded that: (a) In rabbits with normal body store of $Na^+$, the $Fr_{Na}$ of renal tubule beyond proximal tubule. calculated from $C_{Li}$ as a measure of inflow from proximal tubule is constant in spite of variations in $C_{Li}$. (b) The $FrH_2O$ calculated from $C_{Li}$ is dependent largely upon ADH rather than inflow from proximal tubule. (c) When there is a decrease in plasma $Na^+$ concentration or ineffective body fluid. $Li^+$ reabsorption may occur in the thick segnent of Henle's loop and hence the determination of $Fr_{Na}$ and $FrH_2O$ will not be easy one, but $Fr_{Na}$ is constant under the same experimental conditions.

• Childhood Kidney Diseases
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• v.5 no.1
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• pp.36-42
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• 2001

Purpose : Vesicoureteral reflux is the most commonly inherited disease detected in children with urinary tract infection. The incidence of vesicoureteral reflux among siblings of children with known vesicoureteral reflux is 8$\%$ to 45$\%$ according to different authors. Family screening of a patient with vesicoureteral reflux is important in order to prevent reflux nephropathy. The purpose of this study is to determine the incidence of vesicoureteral reflux in asymptomatic family of children with vesicoureteral reflux and the factors which influence the family history. Methods : The study group consisted of 27 families of patients with vesicoureteral reflux. The total number in the group were 79 persons. BUN, Cr, urineanalysis, voidingcystourethrography(VCUG) and 99mTc -dimercaptosuccinic acid(DMSA) renal scan were performed oil tile siblings. As for tile parents the same tests were performed except the VCUG. Results : The abnormality was detected in 7 of 27 families(25.9$\%$). Vesicoureteral reflux was detected in 5 of 20 siblings and renal scar ns detected in 3 of 32 parents. In children with vesicoureteral reflux, renal scar was detected in 24 of 32 children. Between the group with the abnormality in its family(Group A) and the group without the abnormality in its family(Group B), There was no difference of creatinine clearance between two groups. More renal scars were detected in group A according to the DMSA(A:100$\%$, B:75$\%$. t-test P<0.05). There was no difference of grade of VCUG between two groups. There was no difference between one site and both sites in two groups. In tile case of tile siblings with vesicoureteral reflux, there was high incidence of renal scar in a patient with vesicoureteral reflux according to the DMSA. Conclusion : It is important to screen vesicoureteral reflux and renal scar in case of urinary tract infection to prevent reflux nephropathy. This study implies that it is necessary to screen the family of a patient with vesicoureteral reflux especially with renal scar. (J, Korean Soc Pediatr Nephrol 5 : 36- 42, 2001)

• Childhood Kidney Diseases
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• v.7 no.2
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• pp.125-132
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• 2003

Purpose : Lipoprotein(a) is a genetically determined risk factor for atherosclerotic vascular disease and is elevated in patients with renal disease. Especially the patients with nephrotic syndrome exhibit excessively high Lp(a) plasma concentrations. Also the patients with end-stage renal disease have elevated Lp(a) levels. But the mechanism underlying this elevation is unclear. Thus, in this study, by measuring the level of serum Lp(a) in common renal diseases in children, we hoped to see whether there would be a change in Lp(a) in renal diseases other than nephrotic syndrome. Then, we figured out its implications, and looked for the factors that affect the Lp(a) concentrations. Methods : A total of 75 patients(34 patients with hematuria of unknown etiology, 10 with hematuria and hypercalciuria, 8 with IgA nephropathy, 8 with poststreptococcal glomerulone phritis, 3 with $Henoch-Sch\"{o}nlein$ nephritis, 7 with urinary tract infection, and 5 with or- thostatic proteinuria) were studied. The control group included 20 patients without renal and liver disease. Serum Lp(a), total protein, and albumin levels, 24-hour urine protein and calcium excretions, creatinine clearance and the number of RBCs and WBCs in the urinary sediment were evaluated. Data analysis was peformed using the Student t-test and a P-value less than 0.05 was considered to be statistically significant. Results : LP(a) was not correlated with 24-hour urine calcium and creatinine. Lp(a) level had a positive correlation with proteinuria and negative correlation with serum albumin and serum protein. Among the common renal diseases in children, Lp(a) was elevated only in orthostatic proteinuria (P<0.05). Conclusion : Lp(a) is correlated with proteinuria, serum protein, and serum albumin, but not with any kind of specific renal disease. Afterward, Lp(a) needs to be assessed in patients with orthostatic proteinuria and its possible role as a prognostic factor could be confirmed.