• Biomolecules & Therapeutics
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• v.6 no.2
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• pp.151-158
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• 1998

Aspalatone, a new antithrombotic agent, was administered orally to pregnant Sprague-Dawley rats during the organogenetic period at dose levels of 0, 20, 100 and 500 mg/kg/day. All dams were subjected to caesarean section on day 20 of pregnancy. Effects of test substance on dams and embryonic development of F1 fetuses were examined There were treatment-related decreases in body weight and food consumption in the 500 mg/kg group. There was a increase in the spleen weight in the 100 and 500 mg/kg groups. Develo-pmental toxicity was evident as decreased fetal body weights and increased fetal malformations in the 500 mg/ kg group. External and skeletal malformations of fetuses occurred at an incidence of 1 and 8.2%, respectively. In addition, there was a delay in ossification of sternebrae and sacrocaudal vertebrae in the 500 mg/kg group. The results show that the no observed adverse effect dose level (NOAEL) for maternal toxicity was 20 mg/kg/ day and for developmental toxicity was 100 mg/kg/day.

• Hip & pelvis
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• v.34 no.4
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• pp.191-202
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• 2022

The aim of this study was to provide helpful information for use in selection of an appropriate medication after osteoporotic fractures through conduct of a literature review. In addition, a review of the recommendations of several societies for prevention of subsequent fractures was performed and the appropriate choice of medication for treatment of atypical femur fractures was examined. Clinical perspective was obtained and an updated search of literature was conducted across PubMed and MEDLINE and relevant articles were selected. The articles were selected manually according to relevance, and the references for identified articles and reviews were also evaluated for relevance. The following areas are reviewed: Commonly prescribed osteoporosis medications: BPs (bisphosphonates), denosumab, and SERMs (selective estrogen receptor modulators) in antiresorptive medications and recombinant human parathyroid hormone teriparatide, recently approved Romosuzumab in anabolic agents, clinical practice guidelines for the management of osteoporosis, osteoporotic fracture, and atypical femur fracture. Most medications for treatment of osteoporosis do not delay fracture healing and the positive effect of teriparatide on fracture healing has been confirmed. In cases where an osteoporotic fracture is diagnosed, risk assessment should be performed for selection of very high-risk patients in order to prevent subsequent fractures, and administration of anabolic agents is recommended.

• Clinical and Experimental Pediatrics
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• v.56 no.7
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• pp.291-297
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• 2013

Purpose: The aim of this study was to investigate prophylactic treatment effects in Korean patients with severe hemophilia A. Methods: A prospective study of 32 severe hemophilia A patients was conducted with the approval of the Institutional Review Board at the Eulji University Hospital. Two patients received primary prophylaxis; whereas, the other 30 patients were divided into 2 groups-secondary prophylaxis (n=15) and on-demand (n=15)-on the basis of their consent for secondary prophylaxis. A 20-25 IU/kg dose of factor VIII concentrate was administered to the primary and secondary prophylaxis group patients every 3 days for 1 year. The prophylactic effect was evaluated by observing changes in the Pettersson scores, annual number of total and joint bleeds, and factor VIII consumption for 1 year. Results: No moderate or severe bleeding was observed, and the Pettersson scores remained unchanged during the prophylaxis period in the patients who received primary prophylactic treatment. After the treatment was changed from on-demand to secondary prophylaxis, the annual number of total and joint bleeds in the secondary prophylaxis group decreased by $64.4%{\pm}13.0%$ and $70.0%{\pm}15.2%$, respectively. The average increase in Pettersson scores within 1 year was $0.5{\pm}0.8$ and $1.3{\pm}1.1$ in the secondary prophylaxis and on-demand groups, respectively. Prophylactic effects were also observed in patients >17 years who had nearly the same initial Pettersson scores. Conclusion: Intermediate-dose prophylactic treatment may delay hemarthropathy progression and prevent its occurrence in Korean severe hemophilia A patients.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3471-3476
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• 2012

Background and Objective: Histone deacetylase (HDAC) inhibitors represent a promising class of potential anticancer agents for treatment of human malignancies. In this study, we investigated the effect of trichostatin A (TSA), one such HDAC inhibitor, in combination with docetaxel (TXT), a cytotoxic chemotherapy agent or erlotinib, a novel molecular target therapy drug, on lung cancer A549 cells. Methods: A549 cells were treated with TXT, erlotinib alone or in combination with TSA, respectively. Cell viability, apoptosis, and cell cycle distribution were evaluated using MTT (3- (4, 5-dimethylthiazol-2-yl) -2, 5-diphenyltetrazolium bromide) assay, Hochst33258 staining and flow cytometry. Moreover, immunofluorescent staining and Western blot analysis were employed to examine alterations of ${\alpha}$-tubulin, heat shock protein 90 (hsp90), epidermal growth factor receptor (EGFR), and caspase-3 in response to the different exogenous stimuli. Results: Compared with single-agent treatment, co-treatment of A549 cells with TSA/TXT or TSA/erlotinib synergistically inhibited cell proliferation, induced apoptosis, and caused cell cycle delay at the $G_2/M$ transition. Treatment with TSA/TXT or TSA/erlotinib led to a significant increase of cleaved caspase-3 expression, also resulting in elevated acetylation of ${\alpha}$-tubulin or hsp90 and decreased expression of EGFR, which was negatively associated with the level of acetylated hsp90. Conclusions: Synergistic anti-tumor effects are observed between TXT or erlotinib and TSA on lung cancer cells. Such combinations may provide a more effective strategy for treating human lung cancer.

• Natural Product Sciences
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• v.23 no.1
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• pp.35-39
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• 2017

D-chiro-inositol (DCI) is a secondary messenger in insulin signal transduction. It is produced in vivo from myo-inositol via action of epimerase. In this study, we evaluated antitumor activity of DCI against human breast cancer both in vitro and in vivo. In order to determine the inhibitory effects of DCI on growth of human breast cancer cells (MDA-MB-231), two different assessment methods were implemented: MTT assay and mouse xenograft assay. MTT assay demonstrated downturn in cell proliferation by DCI treatment (1, 5, 10, 20 and 40 mM) groups by 18.3% (p < 0.05), 17.2% (p < 0.05), 17.5% (p < 0.05), 18.4% (p < 0.05), and 24.9% (p < 0.01), respectively. Also, inhibition of tumor growth was investigated in mouse xenograft model. DCI was administered orally at the dose of 500 mg/kg and 1000 mg/kg body weight to treat nude mouse for 45 consecutive days. On the 45th day, tumor growth of DCI (500 mg/kg and 1000 mg/kg) groups was suppressed by 22.1% and 67.6% as mean tumor volumes were $9313.8{\pm}474.1mm^3$ and $3879.1{\pm}1044.1mm^3$, respectively. Furthermore, breast cancer stem cell (CSC) phenotype ($CD44^+/C24^-$) was measured using flow cytometry. On the 46th day, CSC ratios of DCI (500 mg/kg) and co-treatment with doxorubicin (4 mg/kg) and DCI (500 mg/kg) group decreased by 24.7% and 53.9% (p < 0.01), respectively. Finally, from tumor recurrence assay, delay of 5 days in the co-treatment group compared to doxorubicin (4 mg/kg) alone group was observed. Based on these findings, we propose that DCI holds potential as an anti-cancer drug for treatment of breast cancer.

• Korean Journal of Metals and Materials
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• v.50 no.10
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• pp.735-743
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• 2012

The aim of this study was to analyze the effect of the cooling rate after heat treatment on the microstructure and mechanical properties of 2507 duplex stainless steels. Heat treatment was carried out at $1050^{\circ}C$ for 1 hr, followed by controlled cooling. The cooling rates were $175.6{\times}10^{-3}^{\circ}C/s$, $47.8{\times}10^{-3}^{\circ}C/s$, $33.3{\times}10^{-3}^{\circ}C/s$, $16.7{\times}10^{-3}^{\circ}C/s$, $11.7{\times}10^{-3}^{\circ}C/s$, $5.8{\times}10^{-3}^{\circ}C/s$ and $2.8{\times}10^{-3}^{\circ}C/s$, which resulted in variations of the microstructure, such as the fractional change of the ferrite phase and sigma phase formation. Fatigue, hardness, impact and tensile tests were performed on the specimens with different cooling rates. The precipitation of the ${\sigma}$ phase caused a hardness increase and a sharp decrease of toughness and tensile elongation. The fatigue limit of the sample with a cooling rate of $5.8{\times}10^{-3}^{\circ}C/s$ was 26 MPa higher than that of the sample with a cooling rate of $175.6{\times}10^{-3}^{\circ}C/s$. Our observations of the fracture surface confirmed that the higher fatigue resistance of the specimen with a cooling rate of $5.8{\times}10^{-3}^{\circ}C/s$ was caused by the delay of the fatigue crack growth, in addition to higher yield strength.

• Archives of Plastic Surgery
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• v.32 no.1
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• pp.12-18
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• 2005

The Transverse rectus abdominis musculocutaneous (TRAM) flap has been commonly used for autologous breast reconstruction. Despite these clinical usefulness, the TRAM flap is prone to partial flap or fat necrosis in especially pedicled flap. To improve flap survival, the surgical delay procedures and pharmacological treatments have been developed. In many studies for the pharmacological treatment, Lipo-$PGE_1$ has demonstrated a marked ability to improve flap survival and it's effect has been proved similar to surgical delay procedure. The purpose of this study is to determine the most effective route of Lipo-$PGE_1$ administration as a pharmacological treatment in TRAM flap of the rat. Fifty male Sprague-Dawley rats weighing 300-350 gm were divided into five groups, One week before flap elevation, Lipo-$PGE_1$($2{\mu}g/kg$) was injected three times in a week and than the left inferior epigastric vessel based TRAM flap ($5.0{\times}3.0cm$) elevated; group I: no procedure before flap elevation; group II: intraperitoneal injection; group III: intravenous injection; group IV: subcutaneous injection; group V: topical application. A flap was assessed at postoperative 7 days by comparison of flap survival rate, vessel counts(H-E stain), and vascular endothelial growth factor(VEGF) protein expressed by Western blot. The results demonstrated that the mean percentages of the flap survival area in group III were significantly higher than that of any other group(p<0.05). The vessel counts of all experimental groups were statistically higher than that of control group(p<0.05). Only in group III, the VEGF protein expression was increased significantly than control group and there are no difference in other experimental groups. In conclusion, the intravenous administration of the Lipo-$PGE_1$ is the most effective on flap survival, and the VEGF induced by Lipo-$PGE_1$ has some positive effects on new vessel formation and flap survival.

• Radiation Oncology Journal
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• v.16 no.3
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• pp.225-231
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• 1998

Purpose : To determine whether TNF-$\alpha$ increases the antitumor effect of radiotherapy in murine syngeneic tumor system. Materials and Methods : Syngeneic murine tumors of MCa-K or MCa-4 (mammary carcinoma), OCa-I (ovarian carcinoma), or HCa-I(hepatocarcinoma were grown in hind legs of C3Hf/HeJ mice. When tumors were grown to 6 mm in mean diameter mice were treated with TNF-$\alpha$, radiation, or combination of the both. Gamma-radiation was given as a single dose of 30 Gy for HCa-I and 15 Gy for other tumors using Cobalt-60 teletherapy unit. A novel TNF-$\alpha$ mutein developed in Korea, was intraperitoneally administered daily at a dose of 10 ug per mouse for 7 days. In combination of radiation and TNF-$\alpha$, the drug was started 1 hour after radiation. Tumor growth delay assay was used to measure the tumor response to the treatment. Results : Among 4 tested tumors, TNF-$\alpha$ alone showed significant antitumor activity in MCa-K and OCa-I tumors, which showed absolute growth delay (AGD) of 5.0 days and 6.5 days, respectively. In combination with radiation, TNF-$\alpha$ showed significant delay of AGD (41.1 days) in OCA-I compared to AGDs of TNF-$\alpha$ alone and radiation, i.e., 6.5 days and 26.9 days, respectively(p<0.05). Enhancement factor was 1.29 in OCa-I, which showed supraadditive effect. TNF-$\alpha$ did not show significant delay of AGDs in the remaining 3 tumors compared to AGDs of TNF-$\alpha$ alone and radiation. Conclusions: TNF-$\alpha$ alone showed antitumor effects in MCa-K and OCa-I. In combination with radiation, TNF-$\alpha$ acted in supraadditive way in OCa-I only. The results of this study imply that the combination of TNF-$\alpha$ and radiation has different therapeutic potential depending on tumor model and further study is advocated.

• Parasites, Hosts and Diseases
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• v.47 no.3
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• pp.213-218
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• 2009

Leishmaniasis is a neglected disease and endemic in developing countries. A lack of adequate and definitive chemotherapeutic agents to fight against this infection has led to the investigation of numerous compounds. The aim of this study was to investigate the effect of RT-01, an organotellurane compound presenting biological activities, in 2 experimental systems against Leishmania amazonensis. The in vitro system consisted of promastigotes and amastigotes forms of the parasite, and the in vivo system consisted of L.amazonensis infected BALB/c mice, an extremely susceptible mouse strain. The compound proved to be toxic against promastigotes and amastigotes. The study also showed that treatment with RT-01 produces an effect similar to that treatment with the reference antimonial drug, Glucantime, in L.amazonensis infected mice. The best results were obtained following RT-01 intralesional administration (720 ${\mu}g$/kg/day); mice showed significant delay in the development of cutaneous lesions and decreased numbers of parasites obtained from the lesions. Significant differences in tissue pathology consisted mainly of no expressive accumulation of inflammatory cells and wellpreserved structures in the skin tissue of RT-01-treated mice compared with expressive infiltration of infected cells replacing the skin tissue in lesions of untreated mice. These findings highlight the fact that the apparent potency of organotellurane compounds, together with their relatively simple structure, may represent a new avenue for the development of novel drugs to combat parasitic diseases.

• Archives of Plastic Surgery
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• v.50 no.4
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• pp.432-442
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• 2023

Background Macrophages play a major role in wound healing and prevent infection from the outside. Polarization conversion of macrophages regulates aspects of inflammation, and two macrophages, M1 (classically activated) and M2 (alternatively activated), exist at both ends of broad-spectrum macrophage polarization. Thus, we aimed to investigate whether macrophage polarization can be artificially regulated. To this end, MgSO4 and small-interfering RNA (siRNA) targeting magnesium transport 1 (MAGT1) were used to investigate the effects of intracellular magnesium (Mg2+) concentrations on the differentiation of macrophages in vitro. Methods THP-1 derived macrophages maintained in a culture medium containing 5 mM MgSO4 and siRNA to inhibit the expression of MAGT1. As comparative groups, THP-1 derived macrophages polarized into M1 and M2 macrophages by treatment with M1, M2 inducer cytokine. The polarization status of each group of cells was confirmed by cell surface antigen expression and cytokine secretion. Results We found that MgSO4 treatment increased CD163 and CD206, similar to the effect noted in the M2 group. The expression of CD80 and HLA-DR was increased in the group treated with MAGT1 siRNA, similar to the effect noted in the M1 group. Functional assays demonstrated that the group treated with MgSO4 secreted higher levels of IL-10, whereas the MAGT1 siRNA-treated group secreted higher levels of IL-6 cytokines. Additionally, the conditional medium of the Mg2+ treated group showed enhanced migration of keratinocytes and fibroblasts. Conclusion Mg2+ can help to end the delay in wound healing caused by persistent inflammation in the early stages.