• Korean Journal of Veterinary Research
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• v.44 no.1
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• pp.15-21
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• 2004

This paper describes the development of $^{99m}Tc$ tricarbonyl cysteine as potential renal function diagnostic radiopharmaceutical and evaluation of its biological characteristics using experimental animals. l-Cysteine was labeled efficiently with $^{99m}Tc$ tricarbonyl precursor $([^{99m}Tc(CO)_3(H_2O)_3)]^{+})$ under 30 min heating at ${75^{\circ}C}$. Labeling yield and stability were analyzed by high performance liquid chromatography (HPLC). The biodistribution property of $^{99m}Tc$ tricarbonyl cysteine in mice and its dynamic imaging profiles in rabbits were carried out. To investigate the excretion mechanism of $^{99m}Tc$ tricarbonyl cysteine, tubular transport inhibition test with probenecid was adopted. $^{99m}Tc$ tricarbonyl cysteine was obtained with a high labeling yield under the moderate condition. The results of biodistribution experiments of $^{99m}Tc$ tricarbonyl cysteine in ICR mice at 3 and 90 min provided that $^{99m}Tc$ tricarbonyl cysteine was very highly accumulated in the kidney and bladder, thereby almost 99% of $^{99m}Tc$ tricarbonyl cysteine was excreted within 90 min post injection. The same results were confirmed by the whole body dynamic images for 30 minutes and static images in rabbits at given time intervals after injection. Renogram of $^{99m}Tc$ tricarbonyl cysteine in rabbits showed that its $T_{max}$ and $T_{1/2}$ of $^{99m}Tc$ tricarbonyl cysteine were $2.33{\pm}0.56$ and $4.30{\pm}0.79$ min, respectively. The $T_{max}$ of $^{99m}Tc$ tricarbonyl cysteine with probenecid pretreatment was $2.30{\pm}0.17$ min, whereas $T_{1/2}$ of that with probenecid pretreatment was $17.0{\pm}32.47$ min. $T_{1/2}$ of $^{99m}Tc$ tricarbonyl cysteine with probenecid pretreatment was significantly different, as compared to the result without probenecid (p<0.0001). The results showed that the excretion of $^{99m}Tc$ tricarbonyl cysteine was extremely affected by probenecid. Therefore, $^{99m}Tc$ tricarbonyl cysteine was rapidly excreted from the kidney principally by the tubular secretion.

• Korean Journal of Pharmacognosy
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• v.12 no.1
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• pp.31-43
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• 1981

In order to determine the effect of Oryeongsan reputed to have diuretic action since Han Dynasty and possible synergetic action of Dianthi Semen, Polygonum avicularis Herba, Kochiae Fructus and Akebiae Lignum, herbs with similar reputation, when added to the above prescription, their decoction powders were solved into distilled water and injected into rabbits through the ear vein. Upon the treatment, the excretion of sodium, potassium and chloride ion together with urine volume was kinetically determined. At the same time the clearance of plasma creatinine and sodium ion was determined and the following results were obtained. Every experimental group demonstrated diuretic action, though feable, of relatively long duration. The diuretic mechanism in the case of Oryeongsan made up by mixing the seperate extracts of individual components and Oryeongsan(A) plus Dianthi Semen was found to be inhibitory effect of renal tubular reabsorption in contrast to the case of Oryeongsan(A) plus Polygonum avicularis Herba, Kochiae Fructus or Akebiae Lignum in which case the diuretic mechanism was found to be glomerular vascular dilatation. The urinary excretion of potassium ion was increased in the case of Oryeongsan(A) plus Dianthi Semen, Kochiae Fructus of Akebiae Lignum whereas in the other cases no similar change was registered. The diuretic action was most remarkable in the case of Oryeongsan(A) plus Polygonum avicularis Herba followed by Oryeongsan(A) plus Kochiae Fructus, Oryeongsan(A) plus Dianthi Semen, extract mixture of individual component of Oryeongsan, Oryeongsan(A) and Oryeongsan(A) plus Akebiae Lignum decreasing order. The duration of diuretic action was found to be 90 minutes in the case of Oryeongsan and mixture of individual component of Oryeongsan, and 60 minutes in the case of Oryeongsan(A) plus Dianthi Semen, Kochiae Fructus or Akebiae Lignum in contrast to the case of Oryeongsan(A) plus Polygonum avicularis Herba which lasted up to 120 minutes.

• Journal of Acupuncture Research
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• v.19 no.2
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• pp.1-13
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• 2002

Objective ; In order to study the effect of Acanthopanax senticosus(AS) aqua-acupuncture manufactured with water soluble fraction and ether soluble fraction on the streptozotocin induced diabetic rats Methods ; The fractions of AS aqua-acupuncture were carried out on corresponding bilateral loci of Bisu(BL20) everyday for 4 weeks. The experimental animals were divided into control group and AS groups(AS water fraction group and AS ether fraction group). Thereafter the levels of serum glucose, total choleterol, HDL, triglyceride, AST, ALT, creatinine, BUN, urinary albumin excretion, index of kidney hypertrophy, heart rate, mean blood pressure and fibronectin in glomeruli and tubular cells were measured. Results ; The increased serum total cholestrol, triglyceride levels, HDL and urinary albumin excretion, the index of kidney hypertrophy, the mean blood pressure and the amount of fibronectin in glomeruli and tubular cells were significantly decreased in the AS groups, showing more significant decrease in the AS water fraction group as compared with the control group. In the serum ALT, AST, creatinine and BUN levels, there were no significant changes in the AS groups as compared with the control group. Conclusion ; According to the above results, it reveals that Acanthopanax senticosus water soluble and ether soluble fraction have the antidiabetic effect, the antilipidemic effect and the inhibitory effect of renal damage. Also, the results showed that Acanthopanax senticosus water soluble fraction is more effective than ether soluble fraction.

• Analytical Science and Technology
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• v.15 no.5
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• pp.482-487
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• 2002

International Olympic Committee (IOC) prohibits the use of carteolol which is one of ${\beta}$-blockers. To prove whether carteolol product was taken or not, the analytical method in urine using GC/MS was established, and metabolism and excretion study were evaluated. As compared with acid hydrolysis, enzyme hydrolysis method was more efficiency. Coefficients of variation for intra-assay precision was around 10%. Error was less than 5% except the concentration of $0.05{\mu}g/m{\ell}$. Recovery was 78.5% at $2{\mu}g/m{\ell}$. Free carteolol, conjugated carteolol, and small amount of p-OH carteolol were found in dosed human urine samples. The conjugated form was being 59.4% of the total carteolol in human urine. The amount of carteolol renal excreted for 72 h after oral dose of 10 mg of carteolol was 49% of the administred dose.

• 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.

• The Korean Journal of Physiology and Pharmacology
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• v.16 no.2
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• pp.91-95
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• 2012

The role of the kidney in combating metabolic acidosis has been a subject of considerable interest for many years. The present study was aimed to determine whether there is an altered regulation of renal acid base transporters in acute and chronic acid loading. Male Sprague-Dawley rats were used. Metabolic acidosis was induced by administration of $NH_4Cl$ for 2 days (acute) and for 7days (chronic). The serum and urinary pH and bicarbonate were measured. The protein expression of renal acid base transporters [type 3 $Na^+/H^+$ exchanger (NHE3), type 1 $Na^+/{HCO_3}^-$ cotransporter (NBC1), Na-$K^+$ ATPase, $H^+$-ATPase, anion exchanger-1 (AE-1)] was measured by semiquantitative immunoblotting. Serum bicarbonate and pH were decreased in acute acid loading rats compared with controls. Accordingly, urinary pH decreased. The protein expression of NHE3, $H^+$-ATPase, AE-1 and NBC1 was not changed. In chronic acid loading rats, serum bicarbonate and pH were not changed, while urinary pH was decreased compared with controls. The protein expression of NHE3, $H^+$-ATPase was increased in the renal cortex of chronic acid loading rats. These results suggest that unaltered expression of acid transporters combined with acute acid loading may contribute to the development of acidosis. The subsequent increased expression of NHE3, $H^+$-ATPase in the kidney may play a role in promoting acid excretion in the later stage of acid loading, which counteract the development of metabolic acidosis.

• Journal of The Korean Society of Clinical Toxicology
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• v.8 no.1
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• pp.24-29
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• 2010

Purpose: Neonicotinoid insecticides are widely used as they have been proven by experimental studies to have low toxicity to mammals, including humans. As the use of neonicotioids increases, the number of patients with neonicotinoid poisoning has also increased. We conducted a study to investigate the clinical manifestations of neonicotinid poisoning. Methods: We retrospectively analyzed the patients who ingested neonicotinids and who visited the emergency department located in Korea from March 2002 to February 2010. We reviewed the patients' age, gender, the amount of exposure, the elapsed time to presentation, the treatment and the outcome. According to the poisoning severity score, we divided the patients with a Poisoning severity score (PSS) of 0 or 1 into the mild/moderate toxicity group and the patients with a PSS of 2 or 3 into the severe/fatal toxicity group. Results: A total of 24 patients were analyzed. The most common clinical manifestations of neonicotinoid insecticide toxicity were gastrointestinal symptoms (66.7%) such as nausea, vomiting and abdominal pain and the others are respiratory symptoms (16.7%), cardiovascular symptoms (12.5%), metabolic imbalance (12.5%), renal dysfunction (8.3%), CNS symptoms (8.3%), and asymptomatic (29.2%). Twenty patients (83.3%) showed mild/moderate toxicity and 4 patients (16.7%) showed fatal conditions such as shock and mutiorgan failure. The mortality rate was 4.2%. In these fatal cases, the patients developed respiratory failure, hypotension, altered mentality and renal failure at the acute stage and they deteriorated to a more serious condition. This severe toxicity was caused by decreased renal excretion of neonicotinid metabolite, and this was improved after hemodialysis. Conclusion: Most patients with neonicotinoid poisoning and who showed mild toxicity usually improved after symptomatic treatment. However, some patients showed significant toxicity with respiratory failure and renal function deterioration, and intensive care needed, including mechanical ventilation and hemodialysis.

• Journal of Nutrition and Health
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• v.30 no.1
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• pp.3-11
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• 1997

This study was conducted to investigate the effects of protein levels and casein/whey ratios on organ growth and protein metabolism in early weaned rats. Premature rats weaned by the 17th day were fed six semipurified synthetic, isocaloric and gel diets that contained three levels (low, medium and high) and two different combinations(casein/whey ; 80 : 20 or 20 : 80) of milk protein for 8 days. On the 25th day postpartum, frest weigth and DNA, RNA and milk protein contents in brain, liver, kidney and muscle were determined to ascertain organ and cellular growth. Futher, with a view to ascertain protein metabolism and renal functions, serum total protein, $\alpha$-amino N, urea N, and creatinine and creatinine and urinary urea N, creatinine and hydroxproline were determined. Total DNA contents of brain, liver and kidney, which may represent as an index of cell numbers in those organs were significantly decreased in the rats fed diets containing low level protein regardless of casein/whey ratio. However, as fat as the rats fed high protein diets were concerned, their fresh weight, protein contents and GFR of kidney were significantly increased. Furthermore, nitrogen components, $\alpha$-amino N, urea N and creatinie in serum and urine were also increassed. Another observation was that high casein/whey ratio significantly facilitated accumulation of porteins in muscle and kidney and urinary hydorxyproline excretion, not affecting the DNA content of those organs. This study showed that low(8%) or high(32%) contents of protein had less desirable effects either on protein metabolism or on organ cellular growth in prematurely weaned rats, whereas there were no effects on general growth and bone strength.

• Journal of Pharmaceutical Investigation
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• v.32 no.3
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• pp.209-213
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• 2002

Diltiazem inhibits calcium channels and Iεads to vascular smooth muscle rεlaxation and negative inotropic and chronotropic effects in the hεart. Diltiazem is almost completely absorbεd after oral administration, but its extent of absolute oral bioavailability is reduced because of considerable first-pass hepatic metabolism. Diltiazem is able to dilate renal vasculature and can increase the glomerular filtration rate and renal sodium excretion. The purpose of this study was to report the pharmacokinetic changes of diltiazem after oral administration of diltiazem, 20 mg/kg, in rabbits coadministered with cimetidine, 20 mg/kg and pretreated twice per day for 3 days at cimetidine dose of 20 mg/kg. The area under the plasma concentration-time curve (AUC) of diltiazem was significantly higher in rabbits pretreated with cimetidine than that in control rabbits (p<0.01), showing about 149% increased relative bioavailability. The peak plasma concentration $(C_{max})$ and elimination half-life of diltiazem were increased significantly (p<0.05) in rabbits pretreated with cimetidine compared with those in control rabbits. This findings could be due to significant reduction of elimination rate constant by pretreated with cimetidine. The effects of cimetidine on the pharmacokinetics of oral diltiazem were more considerable in rabbits pretreated with cimetidine compared with those in control rabbits. The results suggest that the dosage of diltiazem should be adjusted when the drug would be co-administerεd chronically with cimetidine in a clinical situation.

• The Journal of Korean Medicine
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• v.29 no.4
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• pp.133-145
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• 2008

Objectives: The aim of present study was to investigate recovery effects of Hirudo, which has been used clinically in diabetes therapy. Methods: We established three groups: normal, control, Hirudo, and assigned 6 rats to each group. The normal group was not treated by any process and fed by normal saline. The control & Hirudo groups were administered streptozotocin (STZ) to induce diabetes. Hirudo extract was orally administered to the Hirudo group for 10 days. After 8 weeks, the rats were sacrificed and their body weight, 24hrs urinary protein excretion, glucose, albumin, BUN, creatinine, total-cholesterol, LDL-cholesterol, triglyceride in blood, and level of glycation end-product (AGE) and transforming growth factor (TGF-${\beta}1$) in serum were measured. Morphological profiles and morphometric studies of the kidney cortex, renal transforming growth factor (TGF-${\beta}1$) expression, and renal receptor for advanced glycation end-products (RAGE) expression were studied. Results: The following results were obtained. The protein amount in urine per 24hrs of the Hirudo-treated group as compared to the control group was significantly reduced. The BUN and creatinine level in serum of the Hirudo-treated group as compared to the control group was significantly inhibited. The construction change in kidney of the Hirudo-treated group as compared to the control group was significantly inhibited. The factor of the Hirudo-treated group as compared to the control group was significantly inhibited, which induced the construction change in kidney. Conclusions: The above results suggest that Hirudo partially improved the function of the kidney.