• Childhood Kidney Diseases
• /
• v.12 no.2
• /
• pp.143-149
• /
• 2008

Purpose : Urinary N-acetyl-beta-D-glucosaminidase(NAG) and beta 2-microglobulin(B2M) is considered to be a marker of tubulointerstitial injury. The aim of this study was to examine the urinary levels of NAG and B2M in children with various renal diseases. Methods : We studied 21 children(8.9$\pm$4.5 years, Male:Female=14:7) and they were divided into three groups: group I(steroid-sensitive nephrotic syndrome-4 patients), group II(various kinds of glomerulonephritis-4 patients), and group III(normal urinalysis or non-glomerular renal diseases-13 patients). Results : Urinary NAG levels in groups I and II were significantly higher than those in group III(19.4$\pm$11.5 and 30.0$\pm$30.1 vs. 4.7$\pm$3.9, P=0.01), while urinary B2M levels did not differ among the 3 groups, although urinary NAG levels were positively correlated with urinary B2M levels(r=0.49, P=0.03). Urinary NAG and B2M levels were all correlated with proteinuria(r=0.79, P<0.001 and r=0.68, respectively, P=0.001) serum albumin(r=-0.72, P<0.001 and r=-0.57, respectively, P=0.01) and cholesterol(r=0.58, P=0.006 and r=0.56, respectively, P=0.013) levels. Conclusions : Urinary excretions of NAG and B2M are increased in children with steroidsensitive nephrotic syndrome and various kinds of glomerulonephritis, suggesting tubular dysfunction might be present in these diseases.

• Journal of Life Science
• /
• v.14 no.3
• /
• pp.375-384
• /
• 2004

Fibroblast growth factors (FGFs) are known to induce multiple functions in early development, including mesoderm formation, gastrulation movement and antero-posterior patterning. The induction of mesoderm from Xenopus presumptive ectoderm and the combination effect on inducing organs of bFGF(basic FGF) and HGF (Hepatocyte Growth Factor) were studied. Explants were cultured in the combined solution for 3 days to normal embryo arrive at St. 43. These effects on combined dose were examined by histological experiment and by immunohistochemical method. The concentrations of growth factors were tested in 0, 0.5, 1, 10 and also tested in 50 ng/ml of bFGF, and 0, 1, 10, 50 and 100ng/ml of HGF respectively. The synergistic effects were seen in the combined-dose of bFGF and HGF rather than in single dose. Various organs were differentiated and highest inducing effects were seen at the combined concentration of 1 ng/ml of bFGF and 10ng/ml of HGF, and at the concentration 10ng/ml of bFGF and 1 ng/ml of HGF. The bFGF induces various organs from cultured animal cap explants and the effects are time and dose-dependent. HGF is also a potent mitogen for renal tubular cells and for mature hepatocytes in primary culture. Eyes were developed in high percentage at the combined concentration of 1 and 10ng/ml of bFGF, and 1 and 10 ng/ml of HGF. From the induced eye and normal embryonic eye, RPE65 was commonly detected by monoclonal antibodies 40All and 25F5 and the localization of RPE65 was seen by AP reaction.

• Journal of Environmental Health Sciences
• /
• v.37 no.6
• /
• pp.450-459
• /
• 2011

Objectives: Biomarkers in urine are important in assessing exposures to environmental or occupational chemicals and for evaluateing renal function by exposure from these chemicals. Spot urine samples are needed to adjust the concentration of these biomarkers for variations in urine dilution. This study was conducted to evaluate the suitability of adjusting the urinary concentration of cadmium (uCd) and arsenic (uAs) by specific gravity (SG) and urine creatinine (uCr). Methods: We measured the concentrations of blood cadmium (bCd), uCd, uAs, uCr, SG and N-acetyl-${\beta}$-D-glucosaminidase (NAG) activity, which is a sensitive marker of tubular damage by low dose Cd exposure, in spot urine samples collected from 536 individuals. The value of uCd, uAs and NAG were adjusted by SG and uCr. Results: The uCr levels were affected by gender (p < 0.01) and muscle mass (p < 0.01), while SG levels were affected by gender (p < 0.05). Unadjusted uCd and uAs were correlated with SG (uCd: r = 0.365, p < 0.01; uAs: r = 0.488, p < 0.01), uCr (uCd: r = 0.399, p < 0.01; uAs: r = 0.484, p < 0.01). uCd and uAs adjusted by SG were still correlated with SG (uCd: r = 0.360, p < 0.01, uAs: r = 0.483, p < 0.01). uCd and uAs adjusted by uCr and modified uCr ($M_{Cr}$) led to a significant negative correlation with uCr (uCd: r = -0.367, p < 0.01; uAs: r = -0.319, p < 0.01) and $M_{Cr}$ (uCd: r = -0.292, p < 0.01; uAs: r = -0.206, p < 0.01). However, uCd and uAs adjusted by conventional SG ($C_{SG}$) were disappeared from these urinary dilution effects (uCd: r = -0.081; uAs: r = 0.077). Conclusions: $C_{SG}$ adjustment appears to be more appropriate for variations in cadmium and arsenic in spot urine.

• Journal of Preventive Medicine and Public Health
• /
• v.39 no.3
• /
• pp.199-204
• /
• 2006

Objectives: Mercury is a hazardous organ-specific environmental contaminant. It exists in a wide variety of physical and chemical states, each of which has unique characteristics for the target organ specificity. Exposure to mercury vapor and to organic mercury compounds specifically affects the CNS, while the kidney is the target organ for inorganic Hg compounds. Methods: In this study, mercury chloride $(HgCl_2)$ was studied in a renal derived cell system, i.e., the tubular epithelial Madin-Darby canine kidney (MDCK) cell line, which has specific sensitivity to the toxic effect of mercury. MDCK cells were cultured for 6-24 hr in vitro in various concentrations (0.1-100 M) of $HgCl_2$, and the markers of apoptosis or cell death were assayed, including DNA fragmentation, caspase-3 activity andwestern blotting of cytochrome c. The influence of the metal on cell proliferation and viability were evaluated by the conventional MTT test. Results: The cell viability was decreased in a time and concentration dependent fashion: decreases were noted at 6, 12 and 24 hr after $HgCl_2$, exposure. The increases of DNA fragmentation were also observed in the concentrations from 0.1 to 10 M of $HgCl_2$ at 6 hr after exposure. However, we could not observe DNA fragmentation in the concentrations more than 25 M because the cells rapidly proceeded to necrotic cell death. The activation of caspase-3 was also observed at 6 hr exposure in the $HgCl_2$ concentrations from 0.1 to 10 M. The release of cytochrome c from the mitochondria into the cytosol, which is an initiator of the activation of the caspase cascade, was also observed in the $HgCl_2-treated$ MDCK cells. Conclusions: These results suggest that the activation of caspase-3 was involved in $HgCl_2-induced$ apoptosis. The release of cytochrome c from the mitochondria into the cytosol was also observed in the $HgCl_2-treated$ MDCK cells. These findings indicate that in MDCK cells, $HgCl_2$ is a potent inducer of apoptosis via cytochrome c release from the mitochondria.

• Childhood Kidney Diseases
• /
• v.8 no.1
• /
• pp.68-73
• /
• 2004

Both Gitelman syndrome and Bartter syndrome are autosomal recessively inherited renal tubular disorders characterized by hypokalemic metabolic alkalosis, salt wasting and normal to low blood pressure. Gitelman syndrome is caused by mutations in the thiazide-sensitive Na-Cl cotransporter (NCCT) and distinguished from Bartter syndrome, which is associated with mutations of several genes, by the presence of hypomagnesemia and hypocalciuria. In most of the patients with Gitelman syndrome, the disease manifests with transient episodes of muscular weakness and tetany in the adult period, but, often, is asymptomatic. We report here an 11 years-old female with Gitelman syndrome who presented with aggravation of epileptic seizure. The diagnostic work-up showed typical clinical features of metabolic alkalosis, hypokalemia, hypomagnesemia and hypocalciuria. We also identified a heterozygote mutation($^{642}$CGC(Arg)>TGC(Cys)) and an abnormal splicing in the SLC12A3 gene encoding NCCT.

• The Journal of Internal Korean Medicine
• /
• v.26 no.1
• /
• pp.12-47
• /
• 2005

First, mice were dosed with 50mg/kg of streptozotocin(STZ) twice every 24 hours to cause high blood-sugar. Then, after three days, mice were injected with 100mg/kg of STZ again. Two different dosages of Saengjihwangeumja-gami were given to the experiment groups: SA group, 15mg/kg/day, and SB group, 90mg/kg/day, in order to determine the effects of Saengjihwangeumja-gami, which has been known to be good for DM(Diabetes Mellitus). By observing weight and blood-sugar level changes, blood tolerance, the numerical value of BUN(Blood Urea Nitrogen) and creatinine in blood, and through light-electronicmicroscopic and immunohistologic investigations of pancreas and kidneys, the following results were obtained: 1. The experiment groups showed a high suppressive effect of weight-loss. 2. The experiment groups' blood-sugar and blood tolerance showed an effective lowering of blood-sugar levels. 3. The experiment groups did not show any noticeable change in the numerical value of BUN and creatinine in blood compared with that of the control groups. 4. The experiment groups showed a higher Insulin positive reaction of pancreatic islets ${/beta}-cell$ than the control groups. 5. The experiment groups showed a higher immuno-reaction against IGF- II than the control groups. 6. Observation of apoptosis of the pancreatic islets showed that the cells of experiment groups were less injured compared with those of the control groups, and fewer apoptag-positive reaction cells were seen in experiment groups than in the control groups. 7. Uunder electron-microscopy, the insulin-containing granules in pancreatic islets ${/beta}-cells$ had increased more in the experiment groups than in the control groups. 8. Under light microscopy, the injury on the inner & outer membrane of the glomerulus and epithelial cells of capillaries and cells among vessels were fewer in the experiment groups than in the control groups. 9. More apoptag-positive reaction cells in the kidney were seen in the control groups than in the experiment groups. 10. PAS-positive reaction substances had increased more in the substrate among the vessels of a glomerulus belonging to the control group than those of the experiment group. 11. Uunder electron-microscopy, the nucleonic membrane, nucleoplasm and mitochondria of proximal and distal renal tubular were more injured in the control groups than in the experiment groups. In conclusion, strong evidence for the efficacy of Saengjihwangeumja-gami in lowering blood-sugar, and in recovery and generation of pancreatic tissues injured by DM was observed. Results suggest Saengjihwangeumja-gami is an effective treatment for DM. Further study of the principles of blood-sugar dropping effects of Saengjihwangeumja-gami are needed, as well as further study of recovery and regeneration of pancreatic tissues injured by DM.

• Applied Microscopy
• /
• v.27 no.4
• /
• pp.433-452
• /
• 1997

Mongolian gerbil (Meriones unguiculatus) has been as an animal model for studing the neurological diseases such as stroke and epilepsy because of the congenital incompleteries in Willis circle, as well as the investigation of water metabolism because of the long time-survival in the condition of water-deprived desert condition, compared with other species animals. In order to accomplish the this research, first of all another divided the laboratory animals 5 groups of which each group include the 5 animals. In this study were investigated the histological structure in the kidney, measured the plasma osmolalities at the time of sacrifice of indivisual animals, and the body weights every day during water-deprived. The results obtained in this study were summarized as followings: 1. The body weights and decreasing rates of the body weight in water-deprived mongolian gerbil groups were continuosly decreased. 2. The plasma osmolalities were increased from the 5th water-deprived day, after then the gradually increasing reached nearly its equilibrium state at the 10th water-deprived day. 3. The urine volumes were abruptly decreased from the 2th water-deprived day, after then the gradually decreasing patterns were reached nearly its equilibrium state at the 10th day, and stopped the 11th day. 4. In the light microscopical observation of the kidney, glomerular capillary loop thickening, mesangial matrix increasing, sclerosis, glomerular cystic atrophy, interstitial fibrosis, tubular dilatation, mononuclear interstitial inflammation, interstitial mineralization, and hyperplasia of the collecting duct epithelium in the cortex area, were observed from the 10th water deprived day, and the lesions were gradually severe changed as the time lapse. 5. In the electron microscopical findings of the kidney, the degenerative changes of endothelial cell, podocyte and mesangial cell in glomeruli were initially observed on the 10th water-deprived day as well as the degeneration of microvilli and intracellular organelle in the renal tubules.

• Korean Journal of Food Science and Technology
• /
• v.29 no.6
• /
• pp.1264-1268
• /
• 1997

This study was performed to investigate the effects of aluminium treatment on renal damage in rats. Seventy five male Sprague-Dawley strains were divided into five groups; the control, 250 ppm $AlCl_3$, group, 500 ppm AlCl3 group, 250 ppm $Al_2(SO_4)_3$, group, 500 ppm $Al_2(SO_4)_3$ group and kept on the diet for 2 weeks. The body weight gain was more increased in $AlCl_3$, treated of rats but decreased in $Al_2(SO_4)_3$, treated rats than the control, on based in histophysiological examination, in $AlCl_3$, treated group, thyrodization of kidney tubular lumen and interstitial inflammatory cell infiltration, abscess formation were demonstrated and in $Al_2(SO_4)_3$, treated animals destruction of glomeruli and necrosis in kidney cortex by inflammatory cells were shownd. On the other hand, blue-pigmented cast was noted in tubules of $AlCl_3$ administration group whereas focal aluminium accumulation was noted at interstitial tissue in kidney of $Al_2(SO_4)_3$, administration group.

• Reproductive and Developmental Biology
• /
• v.30 no.3
• /
• pp.157-162
• /
• 2006

Endogenous 84 amino acid parathyroid hormone(PTH) is synthesized as a pre-pro hormone by the chief cells of the parathyroid glands. Physiological actions of PTH include regulation of bone metabolism, renal tubular reabsorption of calcium and phosphate, and intestinal calcium absorption. In addition, PTH stimulates new bone formation by extraordinary stimulation of osteoblastic activity and decreasing calcium excretion by the kidney. In this study, we constructed and tested retrovirus vectors designed to express the human parathyroid hormone(hPTH) gene under the control of the tetracycline-inducible promoters. To increase the hPTH gene expression at turn-on state, woodchuck hepatitis virus posttranscriptional regulatory element(WPRE) sequence was also introduced into retrovirus vector at downstream region of either the hPTH gene or the sequence encoding reverse tetracycline-controlled transactivator(rtTA). Transformed primary culture cells(porcine fetal fibroblast, PFF, chicken embryonic fibroblast, CEF) were cultured in the medium supplemented with or without doxycycline(tetracycline derivative) for 48 hours, and induction efficiency was measured by comparing the hPTH gene expression level using two step RT-PCR and ELISA Higher hPTH expression($3{\tims}10^4\;pg/ml,\;5.3{\times}10^4\;pg/ml$) and tighter expression control(up to 8 fold) were observed from the vector in which the WPRE sequence was placed at downstream of the hPTH gene. The resulting tetracycline inducible vector system may be helpful in solving serious physiological disturbance problems which have been a major obstacle in successful production of transgenic animals.

• Korean Journal of Medicinal Crop Science
• /
• v.25 no.4
• /
• pp.231-237
• /
• 2017

Background: Cisplatin is one of the most extensively used chemotherapeutic agents for the treatment of cancer, including bladder, and ovarian cancers. However, it has been shown to induce nephrotoxicity, despite being an outstanding anti-cancer drug. In this study, we investigated the protective effect of dopaol ${\beta}$-D-glucoside (dopaol) on cisplatin-induced nephrotoxicity. Methods and Results: To confirm the protective effect of dopaol on cisplatin-induced nephrotoxicity, HK-2 cells were treated with $20{\mu}M$ cisplatin and $80{\mu}M$ dopaol. Cisplatin increased apoptosis, caspase-3 activity and mitochondrial dysfunction; however pretreatment with $80{\mu}M$ dopaol successfully attenuated apoptosis, caspase-3 activity and mitochondrial dysfunction. To evaluate the protective effect dopaol on cisplatin-induced nephrotoxicity in vivo, we used an animal model (balb/c mice, 20 mg/kg, i.p. once/day for 3 day). The results were similar to those obtained using HK-2 cells; renal tubular damage and neutrophilia induced by cisplatin reduced following dopaol injection (10 mg/kg, i.p. once/day for 3 day). Conclusions: These results indicate that dopaol treatment reduced cisplatin-induced nephrotoxicity in vitro and in vivo, and can be used to treat cisplatin-induced nephrotoxicity. However, further studies are required to determine the toxicity high dose dopaol and the signal pathways involved in its mechanism of action in animal models.