• Biomolecules & Therapeutics
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• v.20 no.3
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• pp.268-272
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• 2012

Nephrotoxicity occurs when kidney-specific detoxification and excretion do not work properly due to the damage or destruction of kidney function by exogenous or endogenous toxicants. Exposure to drugs often results in toxicity in kidney which represents the major control system maintaining homeostasis of body and thus is especially susceptible to xenobiotics. Understanding the toxic mechanisms for nephrotoxicity provides useful information on the development of drugs with therapeutic benefits with reduced side effects. Mechanisms for drug-induced nephrotoxicity include changes in glomerular hemodynamics, tubular cell toxicity, inflammation, crystal nephropathy, rhabdomyolysis, and thrombotic microangiopathy. Biomarkers have been identified for the assessment of nephrotoxicity. The discovery and development of novel biomarkers that can diagnose kidney damage earlier and more accurately are needed for effective prevention of drug-induced nephrotoxicity. Although some of them fail to confer specificity and sensitivity, several promising candidates of biomarkers were recently proved for assessment of nephrotoxicity. In this review, we summarize mechanisms of drug-induced nephrotoxicity and present the list of drugs that cause nephrotoxicity and biomarkers that can be used for early assessment of nephrotoxicity.

• Journal of Nutrition and Health
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• v.28 no.5
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• pp.426-434
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• 1995

The purpose of this study were to investigate the effect of fasting and vitamin B6 repletion on tissue concentration of pyridoxal 5-phosphate and urinary excreteion of 4-pyridoxic acid in vitamin B6 deficient rats. Sixty six rats(6 per group) were fed either a vitamin B6 deficient diet (-B6) or a control diet (+B6) for 6 weeks and then rats were repleted with +B6 diet for 2 weeks. Rats were fasted for 1 and 3 days and for 3 days after repletion. Pyridoxal 5-phosphate (PLP) concentration in plasma, liver, skeletal muscle, and heart muscle and urinary 4-pyridoxic acid (4-PA) excretion were compared. Fasting resulted in a significant increase in PLP concentration in the plasma, liver and heart muscle of rats fed the -B6 diet. Skeletal muscle PLP concentration was significantly decreased in +B6 rats but not in -B6 rats. Following vitamin B6 repletion, PLP concentration in the plasma, liver and heart muscle in previously -B6 rats was similar to the respective concentration in +B6 rats while PLP concentration in the skeletal muscle of previously -B6 rats increased, but it was not reached to that of +B6 rats. At day 1 and 2 of the fast, urinary 4-PT excretion increased in both +B6 and -B6 rats although there was no supply of vitamin B6 due to fasting. These results suggest that vitami B6 is redistributed as PLP when there is a caloric deficit and PLP is supplied by an endogenous source, possibly PLP bound to skeletal muscle glycogen phosphorylase.

• Asian-Australasian Journal of Animal Sciences
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• v.16 no.12
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• pp.1782-1788
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• 2003

A mathematical model has been constructed to estimate the amino acid requirements for growing Taihe silky fowls in early stage. A requirement was taken as the sum of the needs for maintenance, for gain in carcass weight without feathers, and for the feathers. The maintenance requirement was considered to be the sum of the needs for replacing skin and intestinal losses and for the obligatory creatinine excretion in the urine. A comparative slaughter trial and nitrogen balance trials with growing and adult Taihe silky fowls, respectively, were conducted to estimate the parameters in the model. The amino acid requirements were then calculated with the constructed models. The results showed as following: the replacement needs for skin nitrogen loss was determined at 213.41 mg/d for adult male fowls (body weight 1.60 kg); creatinine excretion in these birds was 4.04 mg/d. when fed an nitrogen-free diets, the adult male fowls with body weight 1.60 kg excreted a total of 246.10 mg/d endogenous nitrogen. The net protein requirement for maintenance was estimated at $11.24mg/w_g{^{0.75}}/d$Per gram of body weight gain contained 27.18 mg carcass nitrogen for growing birds in early stage, but feathers nitrogen in per gram of body weight gain increased with age. The amino acid requirements for growing Taihe silky fowls were slightly higher than for starting and growing pullets, but lower than that of broiler chicks. The amino acid requirements patterns changed with weeks of age.

• The Korean Journal of Physiology
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• v.25 no.1
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• pp.37-48
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• 1991

The characteristics of probenecid effect on renal urate excretion in the cat were studied by clearance method and compared with those in the rabbit. In the cat GFR was $3.03{\pm}0.09\;ml/min{\cdot}kg$, and endogenous plasma urate concentration was $1.12{\pm}0.57\;{\mu}g/ml$, which is less than that in the rabbit $(3.33{\pm}0.46\;{\mu}g/ml)$. In the rabbit, $FE_{ur}$ was $1.76{\pm}0.08$ and net urate secretion was observed, while, in the cat $FE_{ur}$ was $0.70{\pm}0.02$ and net reabsorption was observed. In the cat $FE_{ur}$ was dependent on urine flow and independent of plasma urate concentration. In the rabbit $FE_{ur}$ was suppressed by infusion of probenecid $(30\;mg/kg\;-0.6\;mg/kg{\cdot}min)$ into femoral vein. In the cat the same dose of probenecid increased $FE_{ur}$ and concomitantly increased urine flow. Thus, an increase in $FE_{ur}$ by probenecid could be considered to be resulted from a change in urine flow. In the cat infusion of probenecid $(2.5\;mg/kg{\cdot}min)$ into renal artery markedly suppressed $FE_{P\;A\;H}$, but the effects on $FE_{ur}$ and urine flow were similar to those when probenecid was infused into femoral vein. These results indicate that in the cat kidney urate filtered through glomerulus is reabsorbed by a probenecid-insensitive mechanism with no evidence for net secretion.

• The Korean Journal of Physiology
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• v.23 no.2
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• pp.377-391
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• 1989

Recently it was suggested that the endogenous adenosine might be the mediator for the intercellular communication in the regulation of tubuloglomerular feedback control and renin release. Even though the previous data showed more important regulatory roles in the renal hemodynamics and renin release for the A1 adenosine receptor, it has not yet been settled down about the functional subclassification of renal adenosine receptors. The purpose of the present experiment was to clarify the importance of the renal adenosine receptors for the regulations of the hemodynamic, excretory and secretory functions. Experiments have been done in unanesthetized rabbits. Intrarenal arterial infusion of A1 adenosine antagonist, 8-phenyltheophylline, $3{\sim}30\;nmole/min$, increased urine flow, renal hemodynamics and urinary excretion of sodium. Intrarenal arterial infusion of Al antagonist, 1-3-diethyl-8-phenylxanthine (DPX), $10{\sim}100\;nmole/min$, increased renal hemodynamics and excretory functions. Non-specific adenosine antagonist, theophylline, $30{\sim}300\;nmole/min$, resulted in dose dependent increases in renal hemodynamics and excretory function. All of the three adenosine antagonists for the increases in renal hemodynamics, excretory and secretory functions was 8-phenyltheophylline > DPX > theophylline. These results suggest that the endogenous adenosine is important for the intrinsic regulatory roles for the renal functions through the adenosine receptors, and that the A1 adenosine receptor is more important than the A2 receptor in the regulation of renal hemodynamics, excretory and renin secretory functions.

• Journal of the Korean Chemical Society
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• v.41 no.8
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• pp.406-413
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• 1997

The endogenous steroids from human urine were simultaneously analyzed by selected ion monitoring method of GC/MS which is currently used for the doping procedure, together with anabolic steroids. The recovery range of this method was 72.33 %∼94.54% and the RSD values of precision and accuracy test were 1.43%∼10.86%, 0.96%∼9.98%, respectively. Using this method steroids profile was investigated in the urine of male volunteers after oral administration of nine anabolic steroids banned by IOC (International Olympic Committee). Urinary endogenous steroids level was varied specifically according to the excretion tendency of the metabolites of anabolic steroids.

• Journal of Korean Medical classics
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• v.13 no.2 s.17
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• pp.21-21
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• 2000

All living things including human being consist of soul(spirit) and body. Soul is the root of a life and body frames it. I wrote this paper to tell how internal injury due to endogenous etiological factors and affection due to exegenous pathogenic factors, affect the internal organs and the external bodily from. This paper begins with description of the patterns of disharmony of the internal organs. General disorders of each Five-Jang(五藏) an be classified into two types of soul and body. The Liver and the Heart which lead changing to Yang(陽) of vital energy, have close relationship with spiritual symptoms because spirit is related to Yang. The Lung, Kidneys, the Spleen which lead changing to m(陰) of vital energy, mainly connected with physical disorders because body is relatively close to m. The Five-Jang are ruled by the Five-Phases(五行) system and cause troubles with Oche(五體) and the nine body orifice. Otherwise the main function of the Six-Bu(六府) is to receive food, absorb the usuable portions, and transmit and excrete waste. Therefore they can cause such problems as abdominal pain, distention, difficulty in urination, and constipation. The spleen is responsible for sending Grain-Ki)穀氣) 내 that is closely connected with the six-Bu. The Gall bladder takes care of control of giving out spirit. That's why it presents many symptoms related to the spirit that is ruled by the Five-Jang. Patterns of disharmony of external bodily form is influenced by the state of Maridians. Bodily forms get divided into many parts by the function of six-meridians(六經) to which they belong. Six-meridians have their own function related to excretion, related to excretion, retention, and balance(開闔樞). If local bodily froms get affected by pernicious influences, the Meridians to which they are attached will lose harmony and connot fulfil their own functions. Because the meridian symtem unifies all parts of the body, the whole body will be under the influence of the affection although local parts of the bodily forms get affected. Therefore the symptoms of disharmony should be considered in a synthetic view. There are however, also cases which should be focused on the very meridian channels affected. Disorder within a Meridian generates derangement in the pathway make it not to benefit the muscles and skin belong to it. Because the meridians connect the interior organs with the exterior bodily form, they are influenced by each other.

• Journal of Korean Medical classics
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• v.13 no.2 s.17
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• pp.22-42
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• 2000

All living things including human being consist of soul(spirit) and body. Soul is the root of a life and body frames it. I wrote this paper to tell how internal injury due to endogenous etiological factors and affection due to exogenous pathogenic factors, affect the internal organs and the external bodily from. This paper begins with description of the patterns of disharmony of the internal organs. General disorders of each Five-Jang(五藏) an be classified into two types of soul and body. The Liver and the Heart which lead changing to Yang(陽) of vital energy, have close relationship with spiritual symptoms because spirit is related to Yang. The Lung, Kidneys, the Spleen which lead changing to m(陰) of vital energy, mainly connected with physical disorders because body is relatively close to m. The Five-Jang are ruled by the Five-Phases(五行) system and cause troubles with Oche(五體) and the nine body orifice. Otherwise the main function of the Six-Bu(六府) is to receive food, absorb the usable portions, and transmit and excrete waste. Therefore they can cause such problems as abdominal pain, distention, difficulty in urination, and constipation. The spleen is responsible for sending Grain-Ki(穀氣) so that is closely connected with the six-Bu. The Gall bladder takes care of control of giving out spirit. That's why it presents many symptoms related to the spirit that is ruled by the Five-Jang. Patterns of disharmony of external bodily form is influenced by the state of Meridians. Bodily forms get divided into many parts by the function of six-meridians(六經) to which they belong. Six-meridians have their own function related to excretion, related to excretion, retention, and balance(開闔樞). If local bodily forms get affected by pernicious influences, the Meridians to which they are attached will lose harmony and cannot fulfil their own functions. Because the meridian system unifies all parts of the body, the whole body will be under the influence of the affection although local parts of the bodily forms get affected. Therefore the symptoms of disharmony should be considered in a synthetic view. There are however, also cases which should be focused on the very meridian channels affected. Disorder within a Meridian generates derangement in the pathway make it not to benefit the muscles and skin belong to it. Because the meridians connect the interior organs with the exterior bodily form, they are influenced by each other.

• Journal of Pharmaceutical Investigation
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• v.36 no.4
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• pp.283-286
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• 2006

The present study aimed to investigate the interaction of nucleoside analogs with human organic anion transporter 1 and 3(hOAT1 and hOAT3) that play a primary role in the tubular uptake of endogenous and exogenous organic anions in the kidney. The interactions of ddC, ara-C, ara-A and ara-U with hOAT1 and hOAT3 were examined using MDCK cells stably overexpressing hOAT1 or hOAT3. Among the tested drugs, ddC showed the highest affinity to hOAT1 with $IC_{50}$ values of 5.2 mM, while ara-A, ara-C and ara-U weakly inhibited the cellular uptake of $[^3H]-PAH$ in MDCK-hOAT1 cells at 1 mM. In contrast, all the tested drugs did not have any inhibition effect on the cellular uptake of $[^3H]-estrone$ sulfate in MDCK-hOAT3 cells over the drug concentration of 0.01-2 mM, implying that they might not interact with hOAT3. Taken all together, the present study suggests that hOAT1 could weakly interact with nucleoside analogues such as ddC, ara-C, ara-A and ara-U but the interaction with hOAT3 during the urinary excretion of these nucleoside analogues may be negligible in the kidney.

• Journal of the Korean Society of Food Science and Nutrition
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• v.24 no.2
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• pp.346-353
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• 1995

The dietary requirement for zinc to maintain optimally the various metabolic and physiological funcitons is still under study. Human beings adapt to reductions in zinc intake by reducing the rate of growth or zinc excretion. Reductions in dietary zinc beyond the capacity to maintain homeostasis lead to utilization of zinc from an exchangeable pool. Loss of a small, critical amount of zinc from this pool leads to both biochemical and clinical signs of zinc deficiency. Zinc requirements have been assessed by balance studies and factorial method. As tissue zinc status influences endogenous losses and the dietary needs, individuls in good status may require higher amounts of zinc than those in poor status. While plasma zinc is insensitive to reducitons in dietary zinc, it is regarded as a valid, useful indicator of the exchangeable pool of zinc. Plasma metallothionein concentrations may prove useful for identifying poor zinc status. It has been suggested that functional end point measurement is the new direciton for zinc requirement. However, determination of the functional response to a marginal zinc intake is difficult because of the lack of a specific, sensitive indicator of zinc status. Presently, no good method for assessment of human zinc requirements exists.