• Toxicological Research
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• v.30 no.2
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• pp.99-107
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• 2014

Melamine-induced nephrotoxicity is closely associated with crystal formation in the kidney caused by combined exposure to melamine (Mel) and cyanuric acid (CA). However, there are few dosage-finding studies for toxicological evaluation of chronic co-exposure to Mel and CA. The objective of this study was to investigate the possible mechanism by which a Mel and CA mixture lead to renal toxicity in rats. Mel and CA were co-administered to rats via oral gavage for 50 days. Nephrotoxicity was determined by measuring blood urea nitrogen (BUN) and serum creatinine (sCr) levels. Relative kidney weights were significantly increased in rats after co-exposure to Mel+CA (63/6.3 or 630/6.3 mg/kg) mixtures. BUN and sCr levels were significantly increased after Mel and CA co-exposure. Taken together, significant increase in KIM-1, NGAL, and calbindin levels were observed in the urine of rats exposed to Mel+CA (63/6.3 or 630/6.3 mg/kg) compared with the corresponding control group. Histological analysis revealed epithelial degeneration and necrotic cell death in the proximal tubules of the kidney after co-exposure to Mel+CA (63/6.3 or 630/6.3 mg/kg). Our data suggest that Mel-mediated renal toxicity may be influenced by CA concentrations in Mel-contaminated milk or foods.

• Quality Improvement in Health Care
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• v.9 no.2
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• pp.230-240
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• 2002

Background : The purpose of this study was to develop, implement and evaluate the pharmacist intervention program designed to identify and correctly adjust the dosage of $H_2$-receptor antagonists ($H_2RA$) in renally impaired patients and promote timely conversion of $H_2RA$ from IV to PO therapy. Methods : The study population consisted of renally impaired patients who received $H_2RA$ therapy from April 9 to May 8, 2001 at Hallym Medical Center. Each morning a specifically developed software program identified patients with serum creatinine (Scr) greater than 1.2 mg/dl or age greater than 65 years. The pharmacist, then screened the pharmacy profiles of the identified patients to determine if the patient was on $H_2RA$. For these patients on $H_2RA$ with renal impairement the creatinine clearance (CrCl) was calculated using Cockroft & Gault equation. The pharmacist determined the proper dosage for each identified patients based on the calculated CrCl and the oral dosage that would be appropriate for whom IV therapy was no longer indicated. Result : A total of 149 cases (101 patients) were monitored during the study period. The dosage was inappropriately prescribed for renal function in 61 of 149 cases (41%), and of those, pharmacist made recommendations for 58 cases of which 33 cases (57%) were accepted by the physicians. The administration route of H2RA was inappropriately used as IV in 22 of 53 cases (42%), and pharmacist made recommendations for those 22 cases of which 15 cases (68%) were accepted. Conclusion : Monitoring of patients with renal dysfunction by a pharmacist improved the dosing of $H_2RA$ and a dosing program of patients with renal impairment would be of benefit to other clinicians and institutions seeking to optimize patient care.

• Journal of Veterinary Clinics
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• v.33 no.2
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• pp.81-86
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• 2016

Cystatin C is a low molecular weight 13 kilodalton protein. It is known to be a more sensitive marker of glomerular filtration rate than creatinine in humans. The purpose of the present study was to demonstrate the changes of renal markers including cystatin C according to the severity of chronic mitral valve insufficiency (CMVI) and to investigate the clinical relevance of cystatin C as an early renal marker in dogs with CMVI. A retrospective study was performed to assess renal function according to International Small Animal Cardiac Health Council (ISACHC) system classification of heart failure in dogs with CMVI. Thirty seven dogs were divided into a group 1 (healthy dogs ; n = 10), a group 2 (ISACHC I ; n = 10) and a group 3 (ISACHC II-III ; n = 17). In all dogs, serum concentrations of bun (sUr), creatinine (sCr) and cystatin C (sCys-C) were measured with an automated analyzer. In dogs with CMVI, sCys-C concentrations were significantly correlated with sCr concentrations and were independent of age, BW, SBP, and sex. Renal dysfunction tended to occur more frequently as the severity of CMVI increases. In dogs with mild CMVI, only sCys-C concentrations were statistically higher than in healthy dogs. This study demonstrates the clinical relevance of sCys-C. sCys-C may be a valuable renal marker for early diagnosis of renal dysfunction in dogs with CMVI.

• Childhood Kidney Diseases
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• v.23 no.2
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• pp.105-110
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• 2019

Purpose: We sought to determine associations of urinary neutrophil gelatinase-associated lipocalin (NGAL) and liver-type fatty acid-binding protein (L-FABP), known markers of renal injury, with hematuria in children and adolescents. Methods: A total of 112 urine samples from 72 patients aged 2 to 18 years with hematuria were enrolled in this study. Urinary concentrations of NGAL and L-FABP were measured by ELISA and compared between subjects with and without proteinuria and between subjects with and without glomerulonephritis diagnosed by renal biopsy. Results: Urinary concentrations of NGAL and L-FABP/creatinine (Cr) in subjects with proteinuria were not significantly different from those in subjects without proteinuria. They were not significant different between subjects with and without glomerulonephritis either. However, both concentrations of urinary NGAL and L-FABP/Cr were positively associated with urinary protein to creatinine ratio. Their levels had a tendency to be increased when proteinuria developed at later visits in subjects with hematuria only at initial visits. Conclusion: Monitoring urinary NGAL and L-FABP levels in addition to conventional risk factors such as proteinuria and serum creatinine might improve the prediction of renal injury in pediatric patients with hematuria.

• Journal of Nutrition and Health
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• v.52 no.2
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• pp.129-138
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• 2019

Purpose: Medicinal herbs have recently attracted attention as health beneficial foods and source materials for drug development. Recent studies have demonstrated that extracts of Lycium's fruits and roots have a range of physiologically active substances. The extract of Lycium's leaves has been reported to have excellent anti-oxidant and anti-microbial activity, but its anti-inflammatory efficacy is not known. The chlorophyll present in the leaves can act as an anti-oxidant or pro-oxidant depending on the presence of light. Therefore, this study analyzed the anti-inflammatory effects of Lycium's fruit extract (LFE), leaf extract (LLE), and leaf extract with chlorophyll removal (LLE with CR). Methods: This study examined the inhibitory effects of LFE, LLE, and LLE with CR on pro-inflammatory mediator production as well as on the expression of iNOS and COX-2 in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and BALB/c mice. Results: LFE, LLE, and LLE with CR inhibited the production of pro-inflammatory mediators (NO, $TNF-{\alpha}$, IL-6, and $IL-1{\beta}$) and the expression of iNOS and COX-2 in LPS-stimulated RAW 264.7 cells in a dose-dependent manner. Furthermore, the administration of LLE and LLE with CR inhibited the serum pro-inflammatory cytokine levels and suppressed DNA damage in BALB/c mice. In particular, LLE with CR exhibited the highest anti-inflammatory activity. Conclusion: These results suggest that the fruit and leaves of Lycium are potential therapeutic agents against inflammation.

• Journal of Food Hygiene and Safety
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• v.9 no.3
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• pp.123-131
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• 1994

An enzyme-linked immunosorbent assay(ELISA) was developed for the detection of residual gentamicin(GM) in edible animal products. The immunogen(GM-KLH conjugate) and coating antigen(GM-BSA conjugate) were prepared by coupling GM sulfate to keyhole limpet hemocyanin(KLH) and bovine serum albumin(BSA) in the presence of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride, respectively. Polyclonal antibody to GM was produced in rabbits(New Zealand White, female) by using the immunogen and the antibody titer was measured by indirect ELISA. A competitive ELISA was developed using GM-bovine serum albumin conjugate as a coating antigen, GM(as standards or sample), polyclonal antibody to GM, secondary antibody conjugated with horseradish peroxidase as an enzyme, and H2O2 and o-phenylenediamine dihydrochloride as a substrate and a chromophore, respectively. The detection limit of GM was 10 ng/ml and the standard curve of GM(n=26) was linear up to 10 $\mu\textrm{g}$/ml in this competitive ELISA system. There were no cross-reactivities of the partially purified antibody between GM and the various antibiotice such as amikacin, benzyl-penicillin, chloramphenicol, erythromycin, furazlidone, kanamycin, neomycin, oleandomycin, streptomycin, sulfathiazole and thiamphenicol(CR50<0.05%)

• Journal of Nutrition and Health
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• v.34 no.4
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• pp.409-416
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• 2001

In order to evaluate the effect of habitual Na and Ca intake on blood pressure regulation, we measured the habitual dietary intakes of Na and Ca, urinary excretion of Ca, Na and K, and plasma level of renin activity, aldosterone, and indices of Ca metabolism in 27 untreated hypertensive women and 30 age-matched normal women on a free diet. Hypertensive and total subjects were divided into four groups according to habitual dietary intakes of Na and Ca as low Na-low Ca(LNLC), low Na-high Ca(LNHC), high Na-low Ca(HNLC), and high Na-high Ca(HNHC). HNLC hypertensive group showed the lowest level of plasma renin activity, 25-(OH) Vit D$_3$, calcitonin and serum total Ca, and presented the highest level of PTH and urinary excretions of Na/K and Ca/Cr. There were no significant difference in plasma level of aldosterone and urinary excretion of Na and K among four hypertensive groups. When all subjects were divided into four groups according to the same method, HNLC group showed the highest level of blood pressure with no statistical significance and the lowest level of calcitonin and total serum Ca. The above results indicated that renin-aldosterone system and Ca regulating hormone has a mutual relationship in hypertension. Na and Ca may interact each other, rather than affecting independently blood pressure control. As a result, considering the fact that daily balance of Na and Ca intakes affects Na and Ca regulating hormones and urinary excretion of Na and Ca, it may be involved in blood pressure control. These results suggest that maintaining an adequate intake of Ca with less intake of Na may prevent from the risk of hypertension. (Korean J Nutrition 34(4) : 409~416, 2001)

• Asian-Australasian Journal of Animal Sciences
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• v.14 no.9
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• pp.1260-1266
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• 2001

The effect of protein supplementation, $O_2$ concentration and co-culture on the development of embryos produced by nuclear transfer using cultured cumulus cell was investigated. Recipient oocytes and cumulus cells were obtained from the ovaries of the slaughtered Hanwoo cows. Donor cumulus cells were cultured in Dulbecco's modified Eagle medium containing 10% fetal bovine serum at 5% $CO_2$ in air at $38.5^{\circ}C$. The 1 to 6 passages of cumulus cells were isolated and used as donor cells. The in vitro matured oocytes were enucleated and then the isolated donor cells were introduced. One $15{\mu}s$ pulse of 180 volts was applied to induce the fusion between karyoplast and cytoplast. The fused embryos were activated with $10{\mu}M$ calcium ionophore for 5 min and 2 mM 6-dimethylaminopurine for 3 h. To examine the effect of protein supplementation, nuclear transfer (NT) embryos were cultured in one of the following 4 treatments : 1) CR1aa + 3 mg/ml BSA for 7 days ; 2) CR1aa + 10% FBS for 7 days ; 3) CR1aa + 1.5 mg/ml BSA + 5% FBS for 7 days ; and 4) CR1aa + 3 mg/ml BSA for first 3 days and then CR1aa + 1.5 mg/ml BSA + 5% FBS for 4 days. Culture took place at 5% $CO_2$, 5% $O_2$ and 90% $N_2$ at $38.5^{\circ}C$. Although there were no significant differences in cleavage rate among different protein supplements, the rates of blastocyst formation were significantly different. When NT embryos were cultured in the medium supplemented with only BSA, they could develop to only morula not to blastocyst. However, when FBS was supplemented, NT embryos developed to blastocyst stage. In order to investigate the effect of $O_2$ concentration and co-culture, NT embryos were cultured in CR1aa + 1.5 mg/ml BSA + 5% FBS with or without cumulus cell co-culture at an atmosphere of 5% $CO_2$ in air (20% $O_2$) or 5% $CO_2$, 5% $O_2$, 90% $N_2$ (5% $O_2$) at $38.5^{\circ}C$ for 7 days. The percentage of blastocyst development was significantly higher when the NT embryos were cultured at an atmosphere of 5% $O_2$ than that of 20% $O_2$ (p<0.05). However, there was no significant difference between with and without cumulus cell co-culture at an atmosphere of 5% $O_2$ or 20% $O_2$. Fifty embryos were transferred to 25 recipients and 5 recipients were pregnant at 100 days. From 5 pregnant cows, only one cow was delivered of female twin. In conclusion, the embryos reconstructed by enucleation of metaphase II oocytes and introduction of the cycling and quiescent cumulus donor cells in Hanwoo had developmental potential to term after embryo transfer to recipient cows.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.32 no.4
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• pp.470-475
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• 1999

This study was conducted to evaluate the utilization of animal by-product mixture (ABPM) as a dietary animal protein source of fish meal replacer, and to determine the effect of dietary chromic oxide in growing rainbow trout, Oncorhynchus mykiss. ABPM is a mixture of five anmial by-products such as meat and bone meal (MBM) feather meal (FM), squid live, powder(SLP), poultry by-product (PBP) and blood- meal (BM) at a specific weight based ratio. Diet 1 and 2 were formulated on a isonitrogenous and a isocaloric basis of $46.5\%$ crude protein and 16.7 KJ/g diet; diet 1 (WFM 100), $100\%$ of the animal protein source came from white fish meal; diet 2 (ABPM 40), $60\%$ WFM+$40\%$ ABPM as the animal protein source; diet 3 (-Cr) commercial diet without chromic oxide; diet 4 (+Cr), commercial diet with chromic oxide. After eight weeks of feeding trials, fish fed diet 2 had a significantly lower body weight gain (WG) and feed efficiency (FE) than that of fish fed the other diets (P<0.05). When comparing diet 3 with diet 4, no significant differences were found in WG and FE (P>0.05). There were no significant differences on condition factor, hematocrit level, serum phosphorus, bone phosphorus, whole body phosphorus, and bone ash among fish from all four diet groups. Fish fed diet 4 had a significantly higher whole body lipid than that of fish fed the other diets (P<0.05), These results indicated that ABPM could be used less than $40\%$ in growing rainbow trout with a sufficient period of acclimation, In addition, the $0.5\%$ of chromic oxide can be used to determine the apparent digestibility of the nutrients in the feed without any adverse effects on growth and body composition.

• Journal of The Korean Society of Emergency Medicine
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• v.29 no.6
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• pp.663-670
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• 2018

Objective: Radio-contrast abdomino-pelvic computed tomography (APCT) is considered the gold standard diagnostic tool for an acute abdomen in the emergency department. On the other hand, APCT has a risk of contrast-induced nephropathy. Emergency physicians evaluate the creatinine (Cr) level prior to taking a APCT for the above reason but it takes time to evaluation the serum Cr level. This study hypothesized that Cr measured by a point-of-care test (POCT) can shorten the time to making clinically important decisions for patients with an acute abdomen. Methods: This prospective randomized study was conducted between March 2017 and October 2017. The subjects were divided into two groups (Cr measured by laboratory vs. Cr measured by POCT). To analyze the clinical acceptability for creatinine, agreement was demonstrated graphically by Bland-Altman plots. This study compared the time to make a clinically important decision by physicians and the length of stay at the emergency department in both groups. Results: A total of 76 patients were eligible for the study, 38 patients were assigned to each group. There was no statistically significant difference in the time to the first medical examination (P=0.222) and emergency department stay time (P=0.802). On the other hand, the time to recognition of the Cr level (P<0.001), time to performing APCT (P<0.001), time to decision making (P<0.001), and time to initiation of treatment (P<0.001) were shortened significantly in the point-of-care creatinine group. Conclusion: In this study, the POCT for creatinine can allow rapid decision making by shortening the time to performing the radio-contrast APCT than the laboratory for patients with an acute abdomen.