• 대한수의학회지
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• 제44권1호
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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.

• 생약학회지
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• 제12권1호
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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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• 제19권2호
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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.

• 분석과학
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• 제15권5호
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• pp.482-487
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• 2002

Carteolol은 국제올림픽위원회 (IOC)에서 금지약물로 규정하고 있는 ${\beta}$-차단제 중의 하나이다. 본 실험에서는 GC/MS를 사용하여 사람의 소변으로부터 carteolol의 복용여부를 확인하기 위한 검출방법 및 대사와 배설에 대해서 고찰하였다. 이를 위하여 효소 가수분해방법과 산 가수분해방법을 비교하여 보았는데 효소가수분해방법이 더 좋은 결과를 얻을 수 있었다. 효소 가수분해방법을 이용하여 실험한 결과 RSD 10%내외의 정밀도와 $0.05{\mu}g/m{\ell}$를 제외하고는 오차 5%이내의 좋은 정확도를 보여주었으며 회수율은 78.5%로 나타났다. Carteolol은 소변에서 대부분이 free carteolol과 conjugated carteolol로 존재하며 소량의 p-OH-carteolol로 대사됨을 알 수 있었으며 모 약물로 배출되는 양 중 conjugated form이 59.4%로 나타났다. 소변으로 배출된 carteolol의 양을 측정한 결과 복용양의 49%가 복용 후 72시간까지 모 약물로 배출됨을 알 수 있었다.

• 대한핵의학회지
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• 제33권4호
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• pp.398-404
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• 1999

목적: 당뇨병성 신증은 말기 신부전증의 가장 흔한 원인으로서 그 빈도가 증가되고 있다. $^{99m}Tc$-DMSA는 신피질용 방사성 의약품으로 개발되었으며 신피질의 기능 손상 유무를 형태적으로 관찰하기가 용이하다. 저자들은 $^{99m}Tc$-DMSA 신섭취율이 당뇨병 환자에서 단백뇨의 정도에 따라 차이가 있는지를 확인하고, 당뇨병성 신증의 조기 예측인자로서 유용한 지를 알아보고자 하였다. 대상 및 방법: 1996년 1월부터 1997년 12월까지 당뇨병으로 본원에 입원한 145명(남자 64, 여자 81, 평균연령 56세)의 환자를 대상으로 $^{99m}Tc$-DMSA 신스캔을 시행하고 신섭취율을 구하였다. 환자를 24시간 소변의 단백배설량에 따라 정상 단백뇨군(1군), 미세단백뇨군(2군), 현성단백뇨군(3군)으로 구분하여 $^{99m}Tc$-DMSA 신섭취율의 차이 및 $^{99m}Tc$-DMSA 신섭취율과 다른 임상지표들과의 관계를 비교, 분석하였다. 결과: $^{99m}Tc$-DMSA 신섭취율은 2군에서 $40.8{\pm}11.0%$로 1군의 $54.4{\pm}6.3%$보다 의미 있게 낮았으며(p<0.001), 3군의 $27.7{\pm}12.0%$보다는 유의하게 높았다(p<0.001). 각 군에서 $^{99m}Tc$-DMSA 신섭취율은 혈청 크레아티닌치와는 유의한 음의 상관이 있었으며(r=-0.62, p<0.001), 크레아티닌 제거율과는 의미 있는 양의 상관관계를 나타내었다(r=0.70, p<0.001). 결론: 미세단백뇨기 당뇨병 환자의 $^{99m}Tc$-DMSA 신섭취율은 정상 단백뇨를 보인 당뇨병 환자에서보다 유의하게 감소되어 있었으며, 현성단백뇨기의 환자보다 유의하게 높은 것으로 관찰되었다. 따라서 $^{99m}Tc$-DMSA 스캔은 당뇨병 환자에서 당뇨병성 신증을 조기에 진단할 수 있는 객관적인 검사방법으로 유용하다고 생각된다.

• The Korean Journal of Physiology and Pharmacology
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• 제16권2호
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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.

• 대한임상독성학회지
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• 제8권1호
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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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• 제30권1호
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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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• 제32권3호
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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.

• 대한한의학회지
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• 제29권4호
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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.