• Archives of Plastic Surgery
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• v.47 no.3
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• pp.217-222
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• 2020

Background Surgical reconstruction of chronic wounds is often infeasible due to infection, comorbidities, or poor viability of local tissues. The aim of this study was to describe the authors' technique for improving the regenerative and antimicrobial potential of a combination of modified nanofat and platelet-rich plasma (PRP) in nonhealing infected wounds. Methods Fourteen patients met the inclusion criteria. Fat tissue was harvested from the lower abdomen following infiltration of a solution of 1,000 mL of NaCl solution, 225 mg of ropivacaine, and 1 mg of epinephrine. Aspiration was performed using a 3-mm cannula with 1-mm holes. The obtained solution was decanted and mechanically emulsified, but was not filtered. Non-activated leukocyte-rich PRP (naLR-PRP) was added to the solution before injection. Patients underwent three sessions of injection of 8-mL naLR-PRP performed at 2-week intervals. Results Thirteen of 14 patients completed the follow-up. Complete healing was achieved in seven patients (53.8%). Four patients (30.8%) showed improvement, with a mean ulcer width reduction of 57.5%±13.8%. Clinical improvements in perilesional skin quality were reported in all patients, with reduced erythema, increased thickness, and increased pliability. An overall wound depth reduction of 76.6%±40.8% was found. Pain was fully alleviated in all patients who underwent re-epithelization. A mean pain reduction of 42%±33.3% (as indicated by visual analog scale score) was found in non-re-epithelized patients at a 3-month follow-up. Conclusions The discussed technique facilitated improvement of both the regenerative and the antimicrobial potential of fat grafting. It proved effective in surgically-untreatable infected chronic wounds unresponsive to conventional therapies.

• Archives of Plastic Surgery
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• v.44 no.6
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• pp.482-489
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• 2017

Background Polydeoxyribonucleotide (PDRN) is known to have anti-inflammatory and angiogenic effects and to accelerate wound healing. The aim of this study was to investigate whether PDRN could improve peripheral tissue oxygenation and angiogenesis in diabetic foot ulcers. Methods This was a prospective randomized controlled clinical trial. Twenty patients with a non-healing diabetic foot ulcer were randomly distributed into a control group (n=10) and a PDRN group (n=10). Initial surgical debridement and secondary surgical procedures such as a split-thickness skin graft, primary closure, or local flap were performed. Between the initial surgical debridement and secondary surgical procedures, 0.9% normal saline (3 mL) or PDRN was injected for 2 weeks by the intramuscular (1 ampule, 3 mL, 5.625 mg, 5 days per week) and perilesional routes (1 ampule, 3 mL, 5.625 mg, 2 days per week). Transcutaneous oxygen tension ($TcPO_2$) was evaluated using the Periflux System 5000 with $TcPO_2/CO_2$ unit 5040 before the injections and on days 1, 3, 7, 14, and 28 after the start of the injections. A pathologic review (hematoxylin and eosin stain) of the debrided specimens was conducted by a pathologist, and vessel density (average number of vessels per visual field) was calculated. Results Compared with the control group, the PDRN-treated group showed improvements in peripheral tissue oxygenation on day 7 (P<0.01), day 14 (P<0.001), and day 28 (P<0.001). The pathologic review of the specimens from the PDRN group showed increased angiogenesis and improved inflammation compared with the control group. No statistically significant difference was found between the control group and the PDRN group in terms of vessel density (P=0.094). Complete healing was achieved in every patient. Conclusions In this study, PDRN improved peripheral tissue oxygenation. Moreover, PDRN is thought to be effective in improving inflammation and angiogenesis in diabetic foot ulcers.

• Journal of Pharmaceutical Investigation
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• v.31 no.4
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• pp.281-287
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• 2001

Rebamipide is a novel anti-gastric ulcer agent that has been reported to increase the synthesis of mucus, to increase the mucosal concentration of prostaglandin, and to promote rapid ulcer healing. The purpose of the present study was to evaluate the bioequivalence of two rebamipide tablets, $Mucosta^{TM}$ (Otsuka Korea Pharmaceutical Co., Ltd.) and $Rebamide^{TM}$ (Kyung Dong Pharmaceutical Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). The rebamipide release from the two rebamipide tablets in vitro was tested using KP VII Apparatus II method at pH 6.8 dissolution media. Twenty normal male volunteers, $24.20{\pm}2.26$ years in age and $66.19{\pm}9.41\;kg$ in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After one tablet containing 100 mg of rebamipide was orally administered, blood was taken at predetermined time intervals and the concentrations of rebamipide in serum were determined using HPLC method with fluorescence detector. The dissolution profiles of two rebamipide tablets were very similar at pH 6.8 dissolution media. Besides, the pharmacokinetic parameters such as $AUC_t$, $C_{max}\;and\;T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters. The results showed that the differences in $AUC_t$, $C_{max}\;and\;T_{max}$ between two tablets based on the $Mucosta^{TM}$ were -2.57%, 5.77% and -1.47%, respectively. Minimum detectable differences $({\Delta})$ at ${\alpha}=0.05$ and $1-{\beta}=0.8$ were less than 20% (e.g., 12.62% and 17.63% for $AUC_t,\;and\;C_{max}$, respectively). The powers $(1-{\beta})$ at ${\alpha}=0.05$, ${\Delta}=0.2$ for $AUC_t\;and\;C_{max}$ were above 99.00% and 88.56%, respectively. The 90% confidence intervals were within ${\pm}20%$ (e.g., $-9.96{\sim}4.82$ and $-4.54{\sim}16.09$ for $AUC_t\;and\;C_{max}$, respectively). Two parameters met the criteria of KFDA for bioequivalence, indicating that $Rebamide^{TM}$ tablet is bioequivalent to $Mucosta^{TM}$ tablet.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.6 no.2
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• pp.103-111
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• 2003

Purpose: This study was undertaken to evaluate the gastroduodenal pathology and Helicobacter pylori infection in children with upper gastrointestinal symptoms. Methods: One hundred and seven pediatric patients with upper gastrointestinal symptoms were undergone endoscopy at the Gyeongsang National University Hospital from June 1990 to April 1991. Histopathologic examination was done by H & E staining of gastric antral biopsy specimen and gastritis was defined according to the Sydney System. Tissue H. pylori status was evaluated with the urease test using Christensen's urea broth and H & E or Warthin-Starry silver staining of gastric antral biopsy specimen. IgG Immunoblotting were also performed to detect specific anti-H. pylori antibody in these patients. Results: The reasons for endoscopy were recurrent abdominal pain, acute abdominal pain, sallow face, hunger pain, and frequent nausea. Variable degrees of gastric mucosal hyperemia were found in most of the patients. Gastric hemorrhagic spots, gastric ulcer, duodenal ulcer, duodenal erosion, and hemorrhagic duodenitis were rare endoscopic findings. Histologic chronic gastritis was found in 88% of 107 patients. Histologic chronic duodenitis was observed in all 99 patients whose tissue were available. Gastric tissue H. pylori was positive in 57% of 107 patients by one of the ureasetest, H & E staining and Warthin-Starry silver staining. However, gastric tissue H. pylori detection rate was lower in the younger age groups. Anti-H. pylori IgG antibodies were detectable in 96% of 107 patients. Conclusion: Chronic gastroduodenitis and anti-H. pylori IgG antibody were ubiquitous in children with upper gastrointestinal symptoms.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.4 no.1
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• pp.10-17
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• 2001

Purpose: We measured anti-H. pylori IgG in Korean elementary school children living in Shinchon area of Seoul, Korea to evaluate the influence of environmental living standards on H. pylori infection. Methods: IgG antibodies to H. pylori were measured in plasma using a commercial ELISA kit (GAP IgG Helicobacter pylori, Bio-Rad Laboratories Inc., Hercules, CA, USA). Information on environmental status such as place of birth, parental income, type of housing, number of persons in the household, parents' occupation, family history of peptic ulcer disease and gastric cancer was obtained. Statistical analysis was done by Chi-square and logistic regression test using SPSS $7.0^{TM}$ for Windows. Results: Study subjects consisted of 571 children, and the age distribution ranged from 6.0 to 13.6 years with a mean of $9.6{\pm}1.8$ years. Male-to-female ratio was 1.1:1. The seropositive rates of H. pylori infection ranged from 10.4% in children aged 6 years to 30.9% in 12 year-old group, overall 16.8%. The prevalence of H. pylori infection progressively increased with age, but there was no significant difference in seropositive rates among children in different age groups (p=0.06). Seropositive rates of anti-H. pylori IgG on the basis of gender, place of birth, parental income, type of housing, parents' occupation, family history of peptic ulcer disease and gastric cancer showed no statistically significant difference. Interestingly, however, seropositive rate of anti-H. pylori IgG showed statistical significance in relation to number of persons in the household (p=0.003; Odds ratio 1.50 by logistic regression test). Conclusion: These results suggest that number of persons in the household is the most important factor among environmental living standards, and that risk of H. pylori infection increases by increment of 1.5 times as the number of persons in the household increases by one.

• Korean Journal of Medicinal Crop Science
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• v.27 no.2
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• pp.136-142
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• 2019

Background: Agrimonia pilosa Ledeb has been used as a traditional medicine for the treatment of hematuresis and uterine bleeding in Korea. It has been reported to have anti-obesity, anti-diabetes and anti-inflammaotry effect by regulating the inflammatory signaling pathway. However, the preventive effect of Agrimonia pilosa Ledeb on gastritis has not been elucidated. Thus, in the present study, we evaluated the effects of the water extract of Agrimonia pilosa Ledeb (APW) using HCl/EtOH-induced gastritis rat models. Method and Results: Gastritis was induced in rats by HCl/EtOH administration. The rats in each group were orally administered with two doses of APW (100 and 500 mg/kg). Omeprazole was used as a positive control drug. An enzyme-linked immunosorbent assay (ELISA) was used to measure the prostaglandin $E_2$ ($PGE_2$) levels in stomach. The treatment with 500 mg/kg APW reduced the gastric ulcer area. The APW treatment prevented a decreased in $PGE_2$ concentration induced by HCl/EtOH in rats. In the micronucleus test, the ratio of micronucleated polychromatic erythrocytes to polychromatic erythrocytes showed no significant change in the APW-treated group compared with the control group. Conclusions: These results indicate that APW could be used to prevent the gastritis caused by the HCl/EtOH-induced damage to stomach lining. In addition, the APW treatment showed no significant change in results of the micronucleus test. However, further experiments are required to determine how APW influenced the secretion of mucus and gastric acid using the chromosome aberration test and bacterial reverse mutation assay.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.32 no.1 s.55
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• pp.59-64
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• 2006

Crinum asiaticum Linne var. japonicum has long been used as a rheumatic remedy, an anti-pyretic, an anti-ulcer treatment, and for the alleviation of local pain and fever in Korea and Malaysia. In order to investigate the possibility of Crinum asiaticum Linne var. japonicum extract as a cosmetic ingredient, we measured its anti-inflammatory effect by inhibition of iNOS (inducible nitric oxide synthase), and the release of PGE2, IL-6, and IL-8. HPLC experiment after extraction with 95% ethanol at pH 3.5 showed that Crinum asiaticum Linne var. japonicum was mainly composed of lycorine (up to 1%), a well-known immunosuppressant. The content of lycorine varied depending on the type of tissue analyzed and the extraction method. In anti-inflammatory assay for inhibition of nitric oxide formation on lipopolysaccharide (LPS)- activated mouse macrophage RAW 264.7 cells, the ethanolic extract of Crinum asiaticum showed inhibitory activity of NO production in dose-dependent manner ($IC_{50} = 83.5 {\mu}g/mL$). Additional study by RT-PCR demonstrated that the extract of Crinum asiaticum significantly suppressed the expression of the iNOS gene. Moreover, the extract of Crinum asiaticum did not show my cytotoxicity, but did show cell proliferation effect against LPS ($10{\sim}60%$ increase of tell viability). In an assay to determine inhibition of the $H_2O_2$-activated release of PGE2, IL-6, and IL-8 in human normal fibroblast cell lines, the release of PGE2 and IL-6 was almost completely inhibited above concentrations of 0.05% and 1%, respectively. Moreover, the release of IL-8 was completely inhibited over the entire range of concentrations (> 0.0025%). The result showed that the extract of Crinum asiaticum Linne var. japonicum has sufficient anti-inflammatory effect. There-fore, Crinum asiaticum Linne var. japonicum extract may be useful as an ingredient of cosmetic products.

• Clinical and Experimental Pediatrics
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• v.51 no.5
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• pp.492-499
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• 2008

Purpose : Helicobacter pylori infection is one of the most common gastrointestinal infections worldwide; it almost invariably causes chronic gastritis. Pediatric studies may provide important insights into the mucosal immune response of H. pylori-infection, as children are not submitted to environmental factors such as alcohol, tobacco and anti-inflammatory medication. The aim of the present study was to investigate the mucosal immune response against H. pylori in clinically well-defined groups: H. pylori-positive (divided into peptic ulcer disease and gastritis) and H. pylori-negative control. Methods : Antral biopsies were obtained from 45 children undergoing an upper GI endoscopy for dyspeptic symptoms. T cells (CD3+, CD4+, CD8+) and B cells (CD20+) were analyzed by quantitative immunohistochemistry. The correlation of lymphocyte subsets of gastric mucosa with histology was evaluated. Results : T cells (CD3+, CD4+, CD8+) and B cells (CD20+) were significantly increased in the lamina propria of H. pylori-positive group (P<0.01). CD8+ T cells were significantly increased in the lamina propria of the H. pylori-positive peptic ulcer disease (P<0.01). Within the epithelium, only CD4+ T cells were significantly increased in the H. pylori-positive group (P<0.01). Gastric histological parameters had a closer correlation with lymphocytes in the lamina propria than intraepithelial lymphocytes. Conclusion : This study suggests that both T cells and B cells in the lamina propria play important roles in the local immune response of H. pylori-infected children. Furthermore, it remains to be elucidated whether CD8+ T cells in the lamina propria may contribute to peptic ulcer formation in H. pylori-infected children.

• Journal of the Korean Society of Food Science and Nutrition
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• v.37 no.1
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• pp.8-15
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• 2008

Saussurea lappa (SL) has been used to reduce abdominal pain and tenesmus in traditional oriental medicine. SL and major compounds of SL, sesquiterpene lactones, have been suggested to possess various biological effects, including anti-tumor, anti-ulcer, anti-inflammatory, anti-viral and cardiotonic activities. Recently, it has been reported that ethanol extracts from roots of SL have antiproliferative effects on gastric cancer cells. To explore the possibility that SL has chemopreventive effects on prostate cancer, we examined whether the hexane extract of SL (HESL) inhibits the growth of LNCaP human prostate cancer cells. Cells were incubated with various concentrations ($0{\sim}4$ mg/L) of HESL in DMEM/F12 containing 5% charcoal stripped fetal bovine serum. HESL substantially decreased viable cell numbers and induced apoptosis of LNCaP cells in dose-dependent manners. HESL increased the levels of cleaved caspase-8, -9, -7 and -3, and poly (ADP-ribose) polymerase. HESL increased the levels of the pro-apoptotic Bak and truncated-Bid proteins whereas it had no effect on the anti-apoptotic Bcl-2, Bcl-xL, or Mcl-1. The present results indicate that HESL inhibits the growth of human prostate cancer cells by inducing apoptosis, which involves the activation of the caspase cascades.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1997.11a
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• pp.47-50
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• 1997

Drug development began with the finding of biologically active compounds which are obtained by chemical synthesis or from natural sources. The advent of Combinatorial Chemistry is recognized as a strategy which has a potential to change the methodology of research and development(R&D) of new drugs. Drug development has been carried out with diverse strategies. In the past several decades a variety of new methodology have been introduced in R&D. Random screening of accumulated synthetic samples which had been synthesized for development of other drugs led to the discovery of new drugs. The typical examples are anti-asthma drug trimethoquinol and calcium antagonist diltiazem. (herbesser). In particular the latter drug has been used as a calcium antagonist worldwide, however it was first synthesized to find new tranquilizer and this is the reason why diltiazem has benzodiazepam skeleton. The random screening contributed in the finding of new drugs were carried out with whole animal test and it is a standard methodology in R&D of new drugs. Aspirin is the first synthetic non-steroidal antiinflammatory drug(NSAID) and has been used for more than one hundred years. It is the first example of drug developed from natural product. Salicin is the main constituent of willow bark which had been used in Europe for a long time to treat arthritis and aspirin was developed from salicin. Most of NSAID used clinically were developed from the structure of aspirin, however it took 70 years to clarify why aspirin exhibits its antiinflammatory, analgesic and antipyretic activities. The target of aspirin is cyclooxygenase(COX)which is the first enzyme involved in arachidonate cascade leading to the production of prostaglandins(PG) and thromboxan(TX). Side effect of aspirin causing ulcer in stomach is rather serious problem, since aspirin is so popular drug easily obtained in drug store(OTP). This problem is now going to be solved by a new finding on COX, which have two different types, one is constitutionally expressed COX 1 in almost all organs and the other is inducible COX 2. COX 2 is the responsible enzyme in inflammation etc and now the search of COX 2 specific inhibitors is the target of R&D of next generation NSAID.