• Proceedings of the Korean Society of Toxicology Conference
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• 2006.11a
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• pp.55-64
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• 2006

The fetal central nervous system (CNS) is sensitive to diverse environmental factors, such as alcohol, heavy metals, irradiation, mycotoxins, neurotransmitters, and DNA damage, because a large number of processes occur during an extended period of development. Fetal neural damage is an important issue affecting the completion of normal CNS development. As many concepts about the brain development have been recently revealed, it is necessary to compare the mechanism of developmental abnormalities induced by extrinsic factors with the normal brain development. To clarify the mechanism of fetal CNS damage, we used one experimental model in which 5-azacytidine (5AZC), a DNA damaging and demethylating agent, was injected to the dams of rodents to damage the fetal brain. 5AzC induced cell death (apoptosis)and cell cycle arrest in the fetal brain, and it lead to microencephaly in the neonatal brain. We investigated the mechanism of apoptosis and cell cycle arrest in the neural progenitor cells in detail, and demonstrated that various cell cycle regulators were changed in response to DNA damage. p53, the guardian of genome, played a main role in these processes. Further, using DNA microarray analysis, tile signal cascades of cell cycle regulation were clearly shown. Our results indicate that neural progenitor cells have the potential to repair the DNA damages via cell cyclearrest and to exclude highly affected cells through the apoptotic process. If the stimulus and subsequent DNA damage are high, brain development proceeds abnormally and results in malformation in the neonatal brain. Although the mechanisms of fetal brain injury and features of brain malformation afterbirth have been well studied, the process between those stages is largely unknown. We hypothesized that the fetal CNS has the ability to repair itself post-injuring, and investigated the repair process after 5AZC-induced damage. Wefound that the damages were repaired by 60 h after the treatment and developmental processes continued. During the repair process, amoeboid microglial cells infiltrated in the brain tissue, some of which ingested apoptotic cells. The expressions of genes categorized to glial cells, inflammation, extracellular matrix, glycolysis, and neurogenesis were upregulated in the DNA microarray analysis. We show here that the developing brain has a capacity to repair the damage induced by the extrinsic stresses, including changing the expression of numerous genes and the induction of microglia to aid the repair process.

• IMMUNE NETWORK
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• v.2 no.4
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• pp.208-216
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• 2002

Background: Reactive oxygen and nitrogen are produced by rheumatoid arthritis (RA) synovial tissue and can induce mutations in key genes. Normally, this process is prevented by a DNA mismatch repair (MMR) system that maintains sequence fidelity. Key members of the MMR system include MutS${\alpha}$ (comprised of hMSH2 and hMSH6), which can sense and repair single base mismatches and 8-oxoguanine, and MutS${\beta}$ (comprised of hMSH2 and hMSH3), which repairs longer insertion/deletion loops. Methods: To provide further evidence of DNA damage, we analyzed synovial tissues for microsatellite instability (MSI). MSI was examined by PCR on genomic DNA of paired synovial tissue and peripheral blood cells (PBC) of RA patients using specific primer sequences for 5 key microsatellites. Results: Surprisingly, abundant MSI was observed in RA synovium compared with osteoarthritis (OA) tissue. Western blot analysis of the same tissues for the expression of MMR proteins demonstrated decreased hMSH6 and increased hMSH3 in RA synovium. To evaluate potential mechanisms of MMR regulation in arthritis, fibroblast-like synoviocytes (FLS) were isolated from synovial tissues and incubated with the nitric oxide donor S-nitroso-N-acetylpenicillamine (SNAP). Western blot analysis demonstrated constitutive expression of hMSH2, 3 and 6 in RA and OA FLS. When FLS were cultured with SNAP, the RA synovial pattern of MMR expression was reproduced (high hMSH3, low hMSH6). Conclusion: Therefore, oxidative stress can relax the DNA MMR system in RA by suppressing hMSH6. Decreased hMSH6 can subsequently interfere with repair of single base mutations, which is the type observed in RA. We propose that oxidative stress not only creates DNA adducts that are potentially mutagenic, but also suppresses the mechanisms that limit the DNA damage.

• Journal of Genetic Medicine
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• v.2 no.1
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• pp.31-34
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• 1998

The N-methylpurine-DNA glycosylase (MPG), a ubiquitous DNA repair enzyme, removes N-methylpurine and other damaged purines induced in DNA. Tissue-specific mRNA levels of the N-methylpurine-DNA glycosylase (MPG) were investigated in Balb/c mice of four different growing stages; newborn, 1, 4 and 8-weeks postpartum. MPG expressions in the newborn and the 8-week-old mice were the highest in thymus and testis, respectively. The tested tissues of the newborn mice had consistently higher MPG mRNA level than 8-week-old adults except in testis and thymus. The MPG mRNA level in testis was the lowest in the newborn mice, but it attained the highest in the 8-week-old mice. The levels of MPG mRNA among the different tissues in the newborn and the 8-week-old mice were more than 9.0 and 19.0-fold respectively. These results suggest that the of MPG expression was dependent on the growing stage and had tissue-specificity.

• Journal of Korean Foot and Ankle Society
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• v.17 no.4
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• pp.316-320
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• 2013

It has been reported that the gap between the tendon stumps in chronic Achilles tendon rupture is filled with interposed scar tissue. If it was available to use the interposed scar tissue for reconstruction or augmentation of Achilles rupture, possible damage of normal tissues could be avoided. Our results show that direct repair method using interposed scar tissue for chronic Achilles tendon rupture can successfully relieve pain and restore function of the ruptured Achilles tendon in carefully selected patients.

• Biomedical Science Letters
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• v.15 no.1
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• pp.81-86
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• 2009

Lasers are necessity in our life related to the fields of medicine and cosmetic surgery. With 808 nm diode laser and $CO_2$ laser, we made some wounds on a dorsum of rat by laser irradiation. All of irradiations shows thermal effects on the whole region of skin tissues. They make wound damage depending on laser power and irradiation time. Because a collagen is plays an important role in tissue repair, we studied collagen accumulation in wound tissue. For wound healing, collagen accumulation was found in the near region of damage in epidermis and dermis layer of the rat skin. In case of the quantitative analysis of collagen in wound tissue, the amount of collagen in wound tissue by $CO_2$ laser irradiation is higher than that of 808 nm diode laser irradiation. And re-epithelialization was significantly faster in wound by $CO_2$ laser irradiation compared with that of 808 nm diode laser irradiation.

• Journal of Trauma and Injury
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• v.21 no.1
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• pp.8-14
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• 2008

Iatrogenic ureteral injury is a complication that can occur during a variety of pelvic or abdominal surgeries. The most frequent causes are gynecological ones, followed by colon and vascular surgeries. Management of ureteric injury depends on the time of diagnosis and the severity of organ damage. Injuries diagnosed intraoperatively should be treated immediately. Occasionally, intraoperative ureteral injury is overlooked, and symptoms of the late diagnosis of ureteral injury are usually nonspecific; therefore, the diagnosis is delayed for days or weeks postoperatively. Management of injuries diagnosed postoperatively is more complex. There are differing opinions on whether an initial conservative or immediate operative intervention is the best line of action. Delayed repair is suggested on the grounds that it will reduce inflammation and tissue edema. However, many authors are in favor of early repair, perhaps because tissue planes are easier to find before fibrosis becomes too dense. Ureteral injuries occurring at the level of the pelvic brim should be best managed with an end-to-end anastomosis, preferably around a ureteric stent. More distal injuries also should be ideally managed with an end-to-end anastomosis, after excision of the crushed or compromised segments. However, if the remaining distal segment is short, ureteral reimplantation is the procedure of choice. The Boari flap technique for ureteral reimplantation is invaluable in cases with a short proximal segment. Delayed recognition of iatrogenic ureteral injury may be associated with serious complications, so prompt recognition of ureteral injuries is important. Recognition of the injury before closure is the key to easy, successful, and complications-free repair. Increased awareness of the risk for ureteral damage during certain operative maneuvers is vital to prevent injury, and to decrease the incidence of iatrogenic injury. A sound knowledge of abdominal and pelvic anatomy is the best prevention.

• Proceedings of the SCSK Conference
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• 2003.09a
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• pp.338-351
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• 2003

UV radiation is the most dangerous stress factor among permanent environmental impacts on human skin. Consequences of UV exposure are aberrant tissue architecture, alterations in skin cells including functional changes. Nowadays new kinds of outdoor leisure-time activities and changing environmental conditions make the question of sun protection more important than ever. It is necessary to recognize that self-confident consumers do not consider to change their way of life, they demand modern solutions on the basis of new scientific developments. In the past one fundamental principle of cosmetics was the use of physical and organic filter systems against damaging UV-rays. Today new research results demonstrate that natural protecting cell mechanisms can be activated. Suitable biological actives strongly support the protection function not from the surface but from the inside of the cell. A soy seed preparation (SSP) was proven to stimulate natural skin protective functions. The major functions are an increased energy level and the prevention of DNA damage. These functions can I be defined as biological UV protection. The tumor suppressor protein p53 plays a key role in the regulation of DNA repair. p53 must be transferred into the phosphorylated form to work as transcription factor for genes which are regulating the cell cycle or organizing DNA repair. A pretreatment with SSP increases the phosphorylation rate of p53 of chronically UV-irradiated human keratinocytes significantly. According to the same test procedure SSP induces a dramatic increase in the expression of the tumor suppressor protein p14$^{ARF}$ that is supporting the p53 activity by blocking the antagonist of p53, the oncoprotein Mdm2. Mdm2, a ubiquitin E3-ligase, downregulates p53 and at the same time it prevents phosphorylation of p53. The positive influence of the tumor suppressor proteins explains the stimulation of DNA repair and prevention of sunburn cell formation by SSP, which was proven in cell culture experiments. In vivo the increased skin tolerance against UV irradiation by SSP could be confirmed too. We have assumed, that an increased repair potential provides full cell functionality.y.

• The Korean Journal of Pain
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• v.33 no.4
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• pp.395-399
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• 2020

Background: This study aimed to assess the potential efficacy of purified porcine atelocollagen (PAC) for the management of refractory chronic pain due to suspected connective tissue damage. Methods: Patients treated with PAC were retrospectively evaluated. Patients with chronic refractory pain, suspected to have originated from musculoskeletal damage or defects with the evidence of imaging studies were included. Pain intensity, using the 11-point numerical rating scale (NRS), was assessed before the procedure, and 1 month after the last procedure. Results: Eighty-eight patients were finally included for investigation. The mean NRS score was decreased from 5.8 to 4.1 after 1 month of PAC injection (P < 0.001). No independent factor was reported to be directly related to the decrease in NRS score by more than half. Conclusions: Application of PAC may have potential as a treatment option for refractory chronic musculoskeletal pain. PAC might promote tissue recovery, act as a scaffold for repair, or directly reduce inflammation.

• CELLMED
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• v.3 no.3
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• pp.25.1-25.8
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• 2013

Homoeopathically prepared Condurango 30C is traditionally used in amelioration of certain types of cancer by homeopathic practitioners. In this study, ability of Condurango 30C in amelioration of the conventional benzo[a]pyrene (BaP)-induced lung cancer in rat has been tested. After one month of scheduled oral feeding of BaP, lung cancer is routinely developed after four months in rats. Tumorbearing rats were then treated with Condurango 30C for the next one ($5^{th}$), two ($6^{th}$) and three ($7^{th}$) months, respectively, and sacrificed. Efficacy of post-cancer treatment by Condurango 30C was evaluated against controls (placebo) by different study parameters like: body and lung weights, number and diameter of lung tumour nodules, lung architecture, DNA damage, anti-oxidant activity and reactive oxygen species (ROS) accumulation. Administration of this homeopathic remedy caused increase of body weight and decrease of lung weight, decrease in number and diameter of lung tumour nodules, particularly after one and two months of drug treatment. BaP intoxication significantly increased lipid peroxidase (LPO) with concomitant decrease in activities of different antioxidants, while Condurango 30C administration certainly reduce their levels than normal and cancerous groups, notably after one and two months' of drug treatment. Condurango 30C showed capability to induce ROS-mediated cell death evidenced from the study of ROS activities at different time-points. Further, the remedy possibly achieved its anticancer goal through mediation of DNA-nicks that possibly led cancer cells to the apoptotic pathway. Thus, Condurango 30C has anticancer potential in BaP-induced lung cancer of rats via tissue damage recovery and ROS-mediated programmed cell death.

• The Academic Congress of Korean Shoulder and Elbow Society
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• 2009.03a
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• pp.210-210
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• 2009

For a bursal-side retracted laminated rotator cuff tear, simple repair of the retracted bursal-side rotator cuff might be insufficient because the repaired tendon could remain as an intratendinous tear of the rotator cuff. We present a repair method for intratendinous rotator cuff tears using the suture-bridge technique. We believe that this method helps to preserve the remnant rotator cuff tendon without tissue damage and restores the normal rotator cuff footprint in bursal-side delaminated rotator cuff tears.