• Childhood Kidney Diseases
• /
• v.3 no.2
• /
• pp.130-144
• /
• 1999

Purpose : Long-term use of Cyclosporine(CsA) reduce renal blood flow by afferent arteriolar vasoconstriction and lead to chronic pathologic changes of CsA nephrotoxicity - 1) interstitial nephritis(IN); tubular atrophy (TA) and/or interstitial fibrosis(IF),2) arteriolopathy(AP). The Object of this study is to estimate the incidence of chronic pathologic CsA nephrotoxicity by duration of treatment and type of renal disease, relationship between histologic and clinical nephrotoxicity, and optimal duration of CsA therapy. Methods : 102 children with steroid resistant or dependent nephrotic syndrome confirmed by renal biopsy and treated with CsA from 1986 to 1997 were enrolled in this study(58 MCNS, 10 FSGS, 10 MGN, 15 $Henoch-Sch\"{o}nlein$ purpura nephritis with nephrotic syndrome (HSPN) and 9 IgA nephropathy with nephrotic syndrome(IgAN)). CsA was administered for 1yr, 1.5yr, 2yr in 24, 12, 22 MCNS patients and 2, 2, 6 FSGS patients respectively, 1yr, 2yr in MGN and 1yr in HSPN and IgAN. Sequential biopsies were done in all 102 patients after CsA treatment for evaluation of pathologic nephrotoxicity. Results : Complete remission rate was 92.2% (100% in MCNS and MGN, 80% in FSGS, 86.6% in HSPN and 55.5% in IgAN). Incidence of relapse during 6months after CsA treatment was significantly decreased compaed with relapsing spisodes during 6months before CsA treatment in MCNS(P<0.0001) and FSGS(P<0.0001). According to pathologic changes, 71 patients(69.6%) showed no pathological change, 24 patients(23.5%) showed IN and 7 patients(6.8%) showed AP. IN was 16.6%, 33.3%, 27.2% in 1, 1.5, 2 year of CsA treatment group in MCNS. AP was 0%, 16.6%, 9% in 1, 1.5, 2 year of CsA treatment group in MCNS. 14 out of 58 MCNS(24.1%) showed IN and 4 out of 58 MCNS(6.8%) showed AP. Incidence of pathologic change was significantly lower in CsA therapy of <1yr than >1yr(P=0.03). There were no significant difference of incidence of pathologic change in original renal disease, age and sex. Conclusion : Duration of CsA treatment was significant risk factor for nephrotoxicity and optimal duration seemed to be 1 year. Pathologic change due to nephrotoxicity did not correlate with deterioration of renal function and only detectable by renal biopsy.

• Childhood Kidney Diseases
• /
• v.4 no.2
• /
• pp.127-135
• /
• 2000

Purpose: Cyclosporine(CsA) is a potent immunosuppressant but the use of CsA is associated with various side effects, especially nephrotoxicity. In tile kidney, salt depletion activates tile renin-angiotensin-aldosteron(RAS) system and accentuates chronic CsA nephropathy. We postulate that angiotensin converting enzyme inhibitors(ACEI) can prevent chronic CsA nephropathy, since ACEI may inhibit this cascades. This study was aimed to assess the effect of ACEI on chronic cyclosporin nephropathy in salt depleted rats. Methods: 36 Fischer-344 rats were divided into 6 goups. Group I received normal salt diet(NSD). Group II received a low salt diet(LSD). Group III received CsA with a NSD. Group IV received CsA with a LSD. Group V received NSD+CsA with ACEI. Group VI received LSD+CsA with ACEI. Rats were sacrificed after six weeks and the glomerular filtration rate(GFR), serum sodium, potassium and whole blood cyclosporine levels were measured. Renal tissues me sampled for the observation of histological changes. Results: No differences in blood CsA level & serum sodium were found between groups during the course of this experiment. Serum potassium in group VI was significantly increased compared with group IV and V (P<0.05). In groups treated with CsA only and in those where CsA was combined with ACEI, GFR was found to be significantly more decreased in LSD than NSD, and GFR in group V was significantly decreased in comparison with group III (P<0.05). Renal histologic lesions associated with CsA which consisted of cortical interstitial fibrosis, tubular atrophy and hyalinization of arterioles were more severe in tile LSD group. But, no differences were observed between tile groups treated with CsA and ACEI, and the groups treated with only CsA. Conclusion: Salt depletion associated with the activation of the RAS system accentuated chronic CsA nephrotoxicity, but, ACEI could not reduce the functional and morphological changes of salt depleted kidneys, in which nephropathy can be exacerbated in spite of the blocking of the angiotensin II pathway. further studies are required to elucidate whether Am ameliorated the effect of salt-depleted CsA nephrotoxicity upon the effective renal blood flow.

• Korean Journal of Veterinary Research
• /
• v.27 no.2
• /
• pp.277-290
• /
• 1987

This paper dealt with etiological studies on the acute fatal disease of Angora rabbits occurring as a group in Korea. The disease was confirmed as an acute infectious disease caused by virus. The results obtained were summarized as follows: The disease produced a high morbidity in the rearing Angora rabbits and a high mortality in the infected rabbits, and was acute. The infected rabbits died soon without premonitory signs after inappetence. The body temperature of the affected rabbits rose to $40^{\circ}C$ and nearly all deaths occurred within 48 hours after inoculation. In many cases a bloody foam was visible from the nostrils after death. According to the progress of the disease the nervous signs, such as ataxia, paralysis of the legs, and torticollis could be recognized in the some cases. Rabbits that had recovered from the disease were severe emaciation, and bristly and sparse hairs. In macroscopical findings, there were hemorrhage and edema of the lung, hemorrhage or hyperemia of the tracheal and broncheal mucosae, appearance of blood-tinged effusion in the respiratory tract. The principal lesions were found in the liver. Usually the lobular necrosis of the liver cells was progressed, and focal necrosis and hemorrhagic spots of various sizes were often observed in the liver. Liver was as a whole pale. In chronic cases, however, there was a slight liver cirrhosis with the atrophy of the parenchymal cells. The other lesions encountered grossly consisted of swelling and petechiae of the kidney, hyperemia and hemorrhage of the spleen, catarrh of the small intestine, and hyperemia of the brain. The urinary bladder contained a lot of turbid urine or bloody urine and urinary cast, and was distended with the urine. In microscopical findings, the most striking lesions occurred in the liver and may be classified as viral hepatitis. The hepatic lesions were initially characterized by progression from periportal to peripheral necrosis of the lobules with the infiltration of mononuclear cells. Focal necrosis of various sizes, hemorrhage and hyperemia were often observed in the hepatic lobules. In chronic cases, there were intensive infiltration of lymphocytes, proliferation of fibroblasts, appearance of plasmal cells, and atrophy of parenchymal cells in the hepatic tissue. Perivascular lymphocytic infiltration and meningitis were seen in the brain and spinal cord. In the kidney, there were acute glomerulonephritis, hemorrhage, necrosis of the uriniferous tubules, and retention of eosinophilic substance within the renal tubules. Proliferation of fibroblasts and infiltration of mono-nuclear cells were found in the interstitial stroma of the kidney in chronic case. There were also hemorrhage and edema in the lung, hyperemia and hemorrhage in the trachea and bronchus, perivascular lymphocytic infiltration and focal myocardial necrosis in the heart, hyperemia and hemorrhage in the spleen, vacuolization and desquamation of mucous epithelia in the urinary bladder, catarrhal inflammation of the small intestine, hemorrhage in the adrenal cortex and hyperemia in the other organs. In the electron microscopical findings of the hepatic tissue, crystals of viral particles appeared in the cytoplasm of the hepatocytes and the sinusoidal endothelial cells, and the viral particles, were small in size and polygonal. The authors suppose the virus may belong to picornaviridae family of RNA viruses. Also immature virus-like particles, dilated rough endoplasmic reticulum and destruction of nuclear membrane were seen in the hepatocytes. From these results, it is concluded that the sudden death is an acute viral disease characterized by hepatitis and the affected rabbits may be died of viremia.

• YAKHAK HOEJI
• /
• v.48 no.6
• /
• pp.335-344
• /
• 2004

Interleukin-2 (IL-2), a glycoprotein mainly secreted by CD4+ T helper Iymphocytes, has been developed to use recombinant cytokine to augment the immune response against cancer since IL-2 not only stimulates T Iymphocytes but also enhances natural killer (NK) cell activity. In order to evaluate the immunological safety of recombinant mouse IL-2 (rmIL-2) in cancer therapy, renal cell carcinoma was established in the flank by s.c. injection of renca cell line. Tumor-bearing BALB/c mice were treated with I.p. injections with $2{\times}10^5$ Lu rmIL-2. Even though the tumor size was diminished, there were not significant recovery of body and relative lymphoid organ weights including thymic atrophy in rmIL-2 immunotherapy. Distribution ratios of T cell subsets in thymus were analysed using flow cytometry. Without regard to dosage of rmIL-2, the ratio of CD3+CD4-CD8- T cells was increased in accordance with survival of solid tumor but that of CD4+CD8+ T cells was decreased dramatically. Emergence of autoantibodies (ANA, anti-dsDNA, and anti-histone) in blood was measured after rmIL-2 treatment. The results showed that the levels of ANA and anti-dsDNA did not significantly changed, but the level of anti-histone was increased significantly owing to rmIL-2 therapy. These results indicate rmIL-2 immunotherapy is to induce the autoimmune potential, and the anti-histone measurement as a biomarker of autoimmunity is useful in cancer immunotherapy.

• 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.

• Childhood Kidney Diseases
• /
• v.14 no.1
• /
• pp.51-61
• /
• 2010

Purpose : Previous studies have suggested that Chemokine (C-C motif) ligand-2 (CCL-2; also known as MCP-1) and CCL-5 (also known as RANTES) are possibly associated with the pathogenesis of various inflammatory and non-inflammatory renal diseases. The present study was conducted to investigate association of polymorphisms of CCL-2 and CCL-5 genes with childhood IgA nephropathy (IgAN). Methods : The authors analyzed six single nucleotide polymorphisms (SNPs) of CCL-2 and CCL-5 in 196 pediatric IgAN patients and in 285 healthy controls. We compared variations in SNPs between two several sets of IgAN subgroups, allocated by presence of proteinuria (>4 mg/$m^2$/hour), podocyte foot process effacement, and pathologically advanced disease markers, such as interstitial fibrosis, tubular atrophy, or global sclerosis. Results : Genotypic data of IgAN patients and controls showed no significant SNP frequency difference in both of of CCL-2 and CCL-5. Even though two linkage disequilibrium blocks were formed, there was no significance in the haplotype analysis. In the patient subgroup analysis, no SNP of CCL-2 and CCL-5 was found to be associated with the presence of proteinuria, podocyte foot process effacement, and pathologically advanced disease markers. Conclusion : Our data indicate that no association exists between CCL-2 and CCL-5 SNPs and childhood IgAN susceptibility, and presence of proteinuria, podocyte foot process effacement, and pathologic progression of IgAN.

• Clinical and Experimental Pediatrics
• /
• v.51 no.3
• /
• pp.293-298
• /
• 2008

Purpose : The aim of our study was to evaluate the therapeutic response to cyclosporine, time to remission and side effects in steroid resistant nephrotic syndrome (SRNS). Methods : This study included 22 children with idiopathic SRNS who were treated with cyclosporine between June 1989 and August 2006. Medical records were reviewed retrospectively. Results : The mean age of patients at diagnosis was $5.2{\pm}3.3\;years$. The male to female ratio was 1.2:1. Pre-treatment renal biopsies showed minimal change (MCD) in 12 (54.5%), focal segmental glomerulosclerosis (FSGS) in 8 (36.4%), membranous nephropathy (MGN) in one (4.5%) and mesangioproliferative glomerulonephritis in one (4.5%). 15 (68.2%) patients responded to cyclosporine, of whom 11 (91.6%) patients were MCD, 3 (37.5%) patients FSGS, and 1 patient MGN (MCD vs FSGS, P<0.05). The time to remission in patients who responded to cyclosporine was $31.5{\pm}15.2\;days$. Four of the 15 cyclosporine responders maintained complete remission even after cessation of the medication Seven still received cyclosporine, 2 were intermittently treated with steroids after discontinuation of cyclosporine, and two were treated with cyclosporine and steroids. The mean duration of cyclosporine therapy was $546.5{\pm}346.2$, $1,392.9{\pm}439.7$, $439.5{\pm}84.1$, and $433.5{\pm}74.2$ days, respectively. We performed post-treatment biopsies in 8 patients and partial interstitial fibrosis and tubular atrophy were found in two. Conclusion : The thrapeutic response of cyclosporine is good in steroid resistant nephrotic syndrome, especially in minimal change. But, there is a problem of long term cyclosporine dependency.

• Journal of Ginseng Research
• /
• v.23 no.4
• /
• pp.222-229
• /
• 1999

Histopathological study has been carried out to elucidate the protective effect of Korean red ginseng water extract (KRG-WE) on 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced acute toxicity in male guinea pigs. Forty male guinea pigs ($200{\pm}20g$) were divided into 4 groups: normal controls (group 1) received vehicle and saline; group 2 (single TCDD-treated) received TCDD (5 ${\mu}g/kg$, single dose) and saline; group 3 received KRG-WE (200 mg/kg, i.p.) for 2 weeks starting 1 week before TCDD-exposure; group 4 received same dose of KRG-WE for 7 days from the day of TCDD-exposure. Weights of liver, testis, kidney, spleen and lung of the TCDD-exposed guinea pigs were significantly decreased. Thymus was severely shrunken, thereby could not be distinguished from adipose tissue in group 2 animals. Focal interstitial inflammation and fibrosis were observed from the lung parenchyma of group 2 animals. Furthermore, moderate swelling of hepatocyte, diffused aggregates of hemosiderin-laden macrophages from the Prussian blue stained spleen, marked decrease in spermatogenesis, and pyknotic and degenerative changes in the renal tubules were observed from intestinal organs of group 2 animals. On the other hand, histopathological damage was moderately to markedly alleviated in groups 3 and 4, but pretreatment of KRG-WE was more effective than the simultaneous treatment. In particular, TCDD-induced testicular atrophy was significantly attenuated by KRG-WE (p<0.01). From these results, it could be suggested that Korean red ginseng might be a useful herb that prevented TCDD-induced toxicity on liver, testis, kidney and spleen.