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

• Clinical and Experimental Reproductive Medicine
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• v.35 no.4
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• pp.247-265
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• 2008

Objectives: Many types of liver diseases can damage regenerative potential of mature hepatocytes, hepatic progenitor cells or oval cells. In such cases, a stem cell-based therapy can be an alternative therapeutic option. We examined whether human amnion-derived mesenchymal stem cells (HAM) and human umbilical cord-derived stem cells (HUC) could differentiate into hepatocyte-like cells as therapeutic cells for the liver diseases. Methods: HAM and HUC were isolated from the amnion and umbilical cord of the volunteers after a caesarean section with informed consent. In order to differentiate these cells into hepatocyte-like cells, cells were cultivated in hepatogenic medium using culture plates coated with fibronectin. Effects of hepatocyte growth factor, L-ascorbic acid 2-phosphate, insulin premixture fibroblast growth gactor 4, dimethylsulfoxide, oncostatin M and/or dexamethasone were examined on the hepatic differentiation. After differentiation, the cells were analyzed by RT-PCR, immunocytochemistry, immunoblotting, albumin ELISA, urea assay and periodic acid-schiffs staining. Results: Initial fibroblast-like appearance of HAM and HUC changed to a round shape during culture in the hepatogenic medium. However, in all hepatogenic conditions examined, HUC secreted more amounts of albumin or urea into medium than HAM. Expression of some of hepatocyte-specific genes increased and expression of new genes were observed in HUC following cultivation in hepatogenic medium. Results of immunocytochemistry and immunoblotting analyses demonstrated that HUC secreted albumin into the culture medium. PAS staining further demonstrated that HUC could store glycogen inside of the cells. Conclusions: Both HUC and HAM could differentiate into albumin-secreting, hepatocyte-like cells. Under the same hepatogenic conditions examined, HUC more efficiently differentiated into hepatocyte-like cells compared with the HAM. The results suggest that HUC and HAM could be used as sources of stem cells for the cell-based therapeutics such as in liver diseases.

• Journal of Applied Biological Chemistry
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• v.54 no.4
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• pp.279-283
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• 2011

Toll-like receptors (TLRs) play an important role in induction of innate immune responses. The activation of TLRs triggers inflammatory responses that are essential for host defense against invading pathogens. Phenethyl isothiocyanate (PEITC) extracted from cruciferous vegetables has an effect on anti-inflammatory therapy. Dysregulated activation of nuclear factor-${\kappa}$B (NF-${\kappa}$B), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) has been shown to play important roles in the development of certain inflammatory disease. To evaluate the therapeutic potential of PEITC, NF-${\kappa}$B activation and COX-2 and iNOS expression induced by lipopolysaccharide (LPS, TLR4 agonist), polyinosinic-polycytidylic acid (Poly[I:C], TLR3 agonist), 2 kDa macrophageactivating lipopeptide (MALP-2, TLR2 and TLR6 agonist) or oligodeoxynucleotide 1668 (ODN1668, TLR9 agonist) were examined. PEITC inhibits the activation of NF-${\kappa}$B induced by LPS or Poly[I:C] but not by MALP-2 or ODN1668. PEITC also suppressed the iNOS expression induced by LPS or Poly[I:C]. However, PEITC did not suppress COX-2 expression induced by LPS, Poly[I:C], MALP-2, or ODN1668. These results suggest that PEITC has the specific mechanism for antiinflammatory responses.

• Clinical and Experimental Pediatrics
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• v.45 no.4
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• pp.439-448
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• 2002

Purpose : The aim of this study is to determine and compare the effects of adjunctive therapy with different doses of recombinant human granulocyte-colony stimulating factor(rhG-CSF) on reversing sepsis-associated neonatal neutropenia, and their survival rate in a group I/II-type trial. Methods : RhG-CSF was injected subcutaneously to 10 septic-neutropenic neonates with doses of $10{\mu}g/kg$ from Oct. 1995 to Sep. 1996, and was administered to another 12 septic-neutropenic neonates with doses of $5{\mu}g/kg$ from Oct. 1996 to Sep. 1997. Neutrophilic responses and the outcomes of both groups were compared. Results : In the rhG-CSF $10{\mu}g/kg$ treated group and in the $5{\mu}g/kg$ treated group, the absolute neutrophil count(ANC) was $1,065{\pm}89$($mean{\pm}SEM$) and $1,053{\pm}131$, respectively. The only difference between the two groups was the peak ANC at 48 hours. Eight patients from the remaining nine of rhG-CSF $10{\mu}g/kg$ treated group(88.9％) and ten in $5{\mu}g/kg$ treated group(83.3％) survived the sepsis and were discharged without any problems. Conclusions : RhG-CSF can increase the neutrophil count in critically ill septic neutropenic neonats. The survival rate of both groups were up to 90％. This finding suggests that both doses of rhG-CSF may be effective in a therapeutically useful time frame to treat septic neonates with neonatal neutropenia attributable to bone marrow supression or neutrophil consumption.

• Journal of Chest Surgery
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• v.30 no.7
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• pp.677-685
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• 1997

Thromboelastography(TEG) is the unique measure that gives rapid information about the whole clotting process. Simplifying the diagnosis of coagulopathy during operations, TEG can provide an adequate therapy for postoperative bleeding. Remarkable improvement in hemostasis after cardiopulmonary bypass(CPB) has been achieved by the treatment with proteinase inhibitor aprotinin, but the hemostatic mechanism of aprotinin during CPB is still unclear. This study was designed to evaluate the effects of aprotinin on coagulation system during CPB by using TEG. Forty patients who underwent CPB were divided into two groups: aprotinin(2u 106 kallikrein inhibition units, as a single dose into the cardiopulmonary bypass priming solution) treatment group(male 14, female 8, mean age=50.Byears) and no aprotinin treatment(control) group(male 10, female 8, mean age=53.4 years). TEG, activated clotting time, prothrombin time, activated partial thromboplastin time, platelet counts, fibrinogen an (ibrinogen degradation product(FDP) concentrations were checked before and after CPB(30 minutes after neutralization of heparin effect by protamine sulfate). There was no significant difference in other conventional coagulation tests of two groups except postcardiopulmonary bypass FDP concentration in control group, which was significantly increased compared to that in aprotinin group(p<0.05). In TEG variables of both groups, clot formation time(K) and alpha $angle(\alpha^{\circ})$ were significantly increased and decreased, respectively, after CPB(p<0.05), but fibrinolytic index(LYS60) was not changed during CPB. In aprotinin group, reaction time(R) was decreased significantly after CPB(p<0.05) but maximum amplitude(MA) was not changed(p>0.05). On the contrary, R was not changed markedly but MA was decreased significantly in control group after CPB(p<0.05). This result shows that main change in coagulation system during CPB is not hyperfibrinolysis but cecrease in clot strength by platelet dys unction, and the main effect of aprotinin during cardiopulmonary bypass is the maintenance of clot strength to the pre-CPB level by the preservation of platelet function.

• Journal of Chest Surgery
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• v.40 no.7 s.276
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• pp.492-498
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• 2007

Background: Malignant pleural effusion is a common condition in neoplastic patients and palliative therapy is the usual treatment. Talc has been generally accepted to be the most effective sclerosant for chemical pleurodesis, but the optimal route of administration remains controversy. We compared the results of video-assisted thoracoscopic talc poudrage (VTP) with administering a bedside talc slurry through a chest tube (BTS) for the treatment of malignant pleural effusion. Material and Method: From December 2004 to May 2006, 20 patients with malignant pleural effusion underwent chemical pleurodesis via VTP (group A, n=10), and BTS (group B, n=10). Result: The durations of chest tube placement after the procedure were $7.0{\pm}4.0$ days (group A) and $6.7{\pm}3.6$ days (group B). The hospital stays were $24.3{\pm}9.4$ days (group A) and $30.7{\pm}21.5$ days (group B), respectively. The symptoms of dyspnea were much more improved in group A (p-value=0.014) after discharge (mean f/u group $A=8.5{\pm}2.2$ months, group B $8.0{\pm}7.4$ months). The collapsed portions of lung were better expanded in group A than in group B (p-value=0.011). Conclusion: We recommend VTP for the selected patients with malignant pleural effusion because of the advantages of dissecting the fibrous peel to relieve the atelectasis and dyspnea, and excising the pleura for diagnosis with direct viewing of the lesion.

• Radiation Oncology Journal
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• v.17 no.1
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• pp.43-51
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• 1999

Purpose : To discuss the technical aspect of interstitial brachytherapy including method of implant, insertion time of radioactive source, total radiation dose, and complication, we reviewed patients who had diagnoses of soft tissue sarcoma and were treated by conservative surgery, interstitial implant and external beam radiation therapy Materials and Methods : Between May 1995 and Dec. 1997, ten patients with primary or recurrent soft tissue sarcoma underwent surgical resection (wide margin excision) and received radiotherapy including interstitial brachytherapy. Catheters were placed with regular intervals of 1 ~l.5 cm immediately after tumor removal and covering the critical structures, such as neurovascular bundle or bone, with gelform, muscle, or tissue expander in the cases where the tumors were close to those structures. Brachytherapy consisted of high dose rate, iridium-192 implant which delivered 12~15 Gy to 1 cm distance from the center of source axis with 2~2.5 Gy/fraction, twice a day, starting on 6th day after the surgery, Within one month after the surgery, total dose of 50~55 Gy was delivered to the tumor bed with wide margin by the external beam radiotherapy. Results : All patients completed planned interstitial brachytherapy without acute side effects directly related with catheter implantation such as infection or bleeding. With median follow up duration of 25 months (range 12~41 months), no local recurrences were observed. And there was no severe form of chronic complication (RTOGIEORTC grade 3 or 4). Conclusion : The high dose rate interstitial brachytherapy is easy and safe way to minimize the radiation dose delivered to the adjacent normal tissue and to decrease radiation induced chronic morbidity such as fibrosis by reducing the total dose of external radiotherapy in the management of soft tissue sarcoma with conservative surgery.

• Journal of Oral Medicine and Pain
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• v.35 no.3
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• pp.165-175
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• 2010

Valproic acid (VPA) is a well-known anticonvulsive agent and has been used in the treatment of epilepsy for almost 30 years. VPA emerged in 1997 as an antineoplastic agent as well, when findings indicated the substance inhibited proliferation and induced differentiation of primitive neuroectocdermal tumor cells in vivo (Cinatl et al., 1997). Antitmor activity of VPA is associated with its targeting histone deacetylases. Bile acids and their synthetic derivatives induced apoptosis in various kinds of cancer cells and anticancer effects. It has been reported that the synthetic chenodeoxycholic acid (CDCA) derivatives showed apoptosis-inducing activity on various cancer cells in vitro. This study was undertaken to investigate the synergistic apoptotic effect of co-treatment with the histone deacetylases inhibitor, VPA and a CDCA derivative, HS-1200 on human osteosarcoma (HOS) cells. Cell viability was evaluated by trypan-blue exclusion. Induction and augmentation of apoptosis were confirmed by Hoechst staining, flow cytometry (DNA hypoploidy and MMP change), Westen blot analysis and immunofluorescent staining. In this study, HOS cells co-treated with VPA and HS-1200 showed several lines of apoptotic manifestation such as nuclear condensations, the reduction of MMP, the decrease of DNA content, the release of cytochrome c into cytosol, the translocation of AIF onto nuclei, and activation of caspase-7, caspase-3 and PARP whereas each single treated HOS cells did not. Although the single treatment of 1 mM VPA or $25\;{\mu}M$ HS-1200 for 48 h did not induce apoptosis, the co-treatment of them induced prominently apoptosis. Therefore our data provide the possibility that combination therapy of VPA and HS-1200 could be considered as a novel therapeutic strategy for human osteosarcoma.

• Journal of the Korean Society of Food Science and Nutrition
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• v.41 no.12
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• pp.1716-1726
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• 2012

This study was undertaken to evaluate the antihyperglycemic, antilipid peroxidative, and antioxidant effects of the ethanol extracts of Artemisia iwayomogi (Ai) in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced in Sprague-Dawley rats with a single intravenous injection (45 mg/kg b.w.) of STZ. The diabetic rats were then randomized to the diabetic and Ai extract therapy groups which were treated with Ai extract at doses of 1, 2, and 3 g/kg b.w./day, respectively, for 14 days. Oral administration of Ai (2 g/kg b.w.) significantly decreased their intake of food. Dosage of 2 g/kg of the extract significantly decreased blood glucose levels in the glucose level in diabetic rats after 4 day, there was no significant difference observed at 1 and 3 g/kg. A dose of 2 or 3 g/kg of the Ai extract significantly reduced plasma glucose levels in STZ-induced hyperglycemic rats at 7 days. The hypoglycemic effect of Ai at a dose of 2 g/kg was significantly more effective than that of STZ-control. The effect was more pronounced in 2 g/kg than 1 g and 3 g/kg. A significant reduction in triglycerides (TG) and free fatty acids (FFA), and a significant increase in liver glycogen were observed in treated diabetic rats at doses of 2 g/kg after 14 days of treatment. Administration of Ai extracts to diabetic rats showed a significant decrease in liver malondialdehyde (MDA) levels. The activity of superoxide dismutase (SOD) was significantly increased in the 3 g extract-supplemented groups. The activities of glutathione peroxidase (GSH-px) and catalase (CAT) were significantly increased in the 1 g and 3 g extract-supplemented groups. Ai extract significantly increased glutathione-S transferase (GST) activity in a dose-dependent manner compared with treatment in STZ-control rats. Our result supports the fact that the administration of Ai extract is able to reduce hyperglycemia and hyperlipidemia risk, and also reduce the oxidative stress in diabetic rats.

• Journal of Gastric Cancer
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• v.8 no.3
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• pp.120-128
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• 2008

Purpose: Mistletoe extract was widely used for cancer treatment as complementary or alternative therapy in European area from early twenty century. It is currently used as alternative anti-cancer remedy by piecemeal in domestic medical group, however, the anti-cancer mechanism of mistletoe extract was not known precisely until now. In this study the effect of mistletoe extract on gastric cancer was studied vis cell line experiments. Materials and Methods: The SNU719 gastric cancer cell line was used, and ABNOBAviscum-Q and ABNOBAviscum-F were treated to cells as mistletoe extract, or 5-FU and cisplatin were used with mistletoe extract. The cell viability and cell death rate were estimated by CCK-8 assay kit and lactate dehydrogenase (LDH) assay kit in each. Caspase 3 assay kit was used to measure caspase 3 activity. The protein expression amounts of Bcl2, p53, and PTEN were estimated through Western blot analysis. Results: The co-treatments of mistletoe extract Q/F and 5-FU/cisplatin decreased lesser cell viability than only mistletoe treat. Caspase 3 activity was increased 4~6 times in co-treatment of mistletoe extracts and 5-FU than control. Bcl2 protein expression was reduced by mistletoe extracts or anti-cancer drugs, further more, the co-treatment of mistletoe extracts and 5-FU/cisplatin diminished more the expression than only mistletoe treatment. Mistletoe extracts did not affect the protein expressions of p53 and PTEN. Conclusion: It was concluded that the anti-cancer mechanism of mistletoe extracts was made by caspase 3 activation and lowered Bcl2 expression, and this apoptosis inducing mechanism was independent to p53.