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Nitric Oxide Synthase Inhibitor Decreases NMDA-Induced Elevations of Extracellular Glutamate and Intracellular $Ca^{2+}$ Levels Via a cGMP-Independent Mechanism in Cerebellar Granule Neurons

  • Oh, Sei-Kwan;Yun, Bong-Sik;Ryoo, In-Ja;Patrick P.McCaslin;Yoo, Ick-Dong
    • Archives of Pharmacal Research
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    • v.22 no.1
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    • pp.48-54
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    • 1999
  • These studies were designed to examine the differential effect of nitric oxide (NO) and cGMP on glutamate neurotransmission. In primary cultures of rat cerebellar granule cells, the glutamate receptor agonist N-methyl-D-aspartate (NMDA) stimulates the elevation of intracellular calcium concentration ($[Ca^{2+}]_i$), the release of glutamate, the synthesis of NO and an increase of cGMP. Although NO has been shown to stimulate guanylyl cyclase, it is unclear yet whether NO alters the NMDA-induced glutamate release and ${[Ca^{2+}]}_i$ elevation. We showed that the NO synthase inhibitor, NG-monomethyl-L-arginine (NMMA), partially prevented the NMDA-induced release of glutamate and elevation of ${[Ca^{2+}]}_i$ and completely blocked the elevation of cGMP. These effects of NO on glutamate release and [Ca2+]i elevation were unlikely to be secondary to cGMP as the cGMP analogue, dibutyryl cGMP (dBcGMP), did not suppress the effects of NMDA. Rather, dBcGMP slightly augmented the NMDA-induced elevation of ${[Ca^{2+}]}_i$ with no change in the basal level of glutamate or ${[Ca^{2+}]}_i$. The extracellular NO scavenger hydroxocobalamine prevented the NMDA-induced release of glutamate providing indirect evidence that the effect of NO may act on the NMDA receptor. These results suggest that low concentration of NO has a role in maintaining the NMDA receptor activation in a cGMP-independent manner.

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Identification of the+1 Ribosomal Frameshifting Site of LRV1-4 by Mutational Analysis

  • Kim Se Na;Choi Jung Ho;Park Min Woo;Jeong Sun Joo;Han Kyung Sook;Kim Hong Jin
    • Archives of Pharmacal Research
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    • v.28 no.8
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    • pp.956-962
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    • 2005
  • Leishmania virus (LRV)1-4 has been reported to produce a fusion of ORF2 and ORF3 via a programmed +1 frameshift in the region where ORF2 and ORF3 overlap (Lee et a/., 1996). However, the exact frameshift site has not been identified. In this study, we compared the frameshift efficiency of a 259bp (nt. 2565-2823), frameshift region of LRV1-4, and the 71 bp (nt. 2605-2678) sub-region where ORF2 and ORF3 overlap. We then predicted the frameshift site using a new computer program (Pseudoviewer), and finally identified the specific region associated with the mechanism of the LRV1-4's+1 frameshift by means of a mutational analysis based on the predicted structure of LRV1-4 RNA. The predicted structure was confirmed by biochemical analysis. In order to measure the frameshift efficiency, constructs that generate luciferase without a frameshift or with a+1 frameshift, were generated and in vitro transcription/translation analysis was performed. Measurements of the luciferase activity generated, showed that the frameshift efficiency was about $1\%$ for both the 259bp (LRV1-4 259FS) and 71 bp region (LRV1-4 71FS). Luciferase activity was strongly reduced in a mutant (LRV1-4 NH: nt. 2635-2670) with the entire hairpin deleted and in a mutant (LRV1-4 NUS: nt. 2644-2659) with the upper stem of the hairpin deleted. These results indicate that the frameshift site in LRV1-4's is in the 71 bp region where ORF2 and ORF3 overlap, and that nt. 2644-2659 (the upward hairpin stem) playa key role in generating the +1 frameshift.

A Study on the Genetic Inheritance of Ankyloglossia Based on Pedigree Analysis

  • Han, Soo-Hyung;Kim, Min-Cheol;Choi, Yun-Seok;Lim, Jin-Soo;Han, Ki-Taik
    • Archives of Plastic Surgery
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    • v.39 no.4
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    • pp.329-332
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    • 2012
  • Background Ankyloglossia or tongue-tie is a congenital anomaly characterized by an abnormally short lingual frenum. Its prevalence in the newborn population is approximately 4%. Its mode of inheritance has been studied in some articles, but no conclusion has been established. Also, no relevant report has been published in Korea. This study was conducted to elucidate the genetic inheritance of ankyloglossia via pedigree analysis. Methods In this study, 149 patients with no other congenital anomaly who underwent frenuloplasty between March 2001 and March 2010 were studied. Pedigrees were made via pre- or post-operative history taking, and patients with uncertain histories were excluded. In the patient group that showed a hereditary nature, the male-to-female ratio, inheritance rate, and pattern of inheritance were investigated. Results One hundred (67.11%) of the patients were male and 49 (32.89%) were female (male-female ratio=2.04:1). Ninety-one (61.07%) patients reported no other relative with ankyloglossia, and 58 (38.93%) patients had a relative with this disease. The inheritance rate was 20.69% in the 58 cases with a hereditary nature. In the group with no family history of ankyloglossia, the male-female ratio was 3.79:1, which significantly differed from that of the group with a family history of ankyloglossia. X-chromosome mediated inheritance and variation in the gene expression was revealed in the pedigree drawn for the groups with hereditary ankyloglossia. Conclusions Ankyloglossia has a significant hereditary nature. Our data suggest X-linked inheritance. This study with 149 patients, the first in Korea, showed X-linked inheritance in patients with a sole anomaly.

Use of the Anterolateral Thigh and Vertical Rectus Abdominis Musculocutaneous Flaps as Utility Flaps in Reconstructing Large Groin Defects

  • Aslim, Edwin Jonathan;Rasheed, Mohamed Zulfikar;Lin, Fangbo;Ong, Yee-Siang;Tan, Bien-Keem
    • Archives of Plastic Surgery
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    • v.41 no.5
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    • pp.556-561
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    • 2014
  • Background Groin dissections result in large wounds with exposed femoral vessels requiring soft tissue coverage, and the reconstructive options are diverse. In this study we reviewed our experience with the use of the pedicled anterolateral thigh and vertical rectus abdominis musculocutaneous flaps in the reconstruction of large groin wounds. Methods Groin reconstructions performed over a period of 10 years were evaluated, with a mean follow up of two years. We included all cases with large or complex (involving perineum) defects, which were reconstructed with the pedicled anterolateral thigh musculocutaneous or the vertical rectus abdominis musculocutaneous (VRAM) flaps. Smaller wounds which were covered with skin grafts, locally based flaps and pedicled muscle flaps were excluded. Results Twenty-three reconstructions were performed for large or complex groin defects, utilising the anterolateral thigh (n=10) and the vertical rectus abdominis (n=13) pedicled musculocutaneous flaps. Femoral vein reconstruction with a prosthetic graft was required in one patient, and a combination flap (VRAM and gracilis muscle flap) was performed in another. Satisfactory coverage was achieved in all cases without major complications. No free flaps were used in our series. Conclusions The anterolateral thigh and vertical rectus abdominis pedicled musculocutaneous flaps yielded consistent results with little morbidity in the reconstruction of large and complex groin defects. A combination of flaps can be used in cases requiring extensive cover.

New Bone Formation in Experimental Model of Vascularized Periosteal Flap for the Bone Defect in the Shaft of the Radius of Rabbit - Radiological, Histological and Immunohistochemical Study - (가토 요골 간부 골 결손시에 혈관 부착 골막 보존 유무에 따른 신생골 형성에 대한 실험적 연구)

  • Chung, Duke-Whan;Yum, Jae-Kwang;Tae, Suk-Kee;Ko, Kwang-Won
    • Archives of Reconstructive Microsurgery
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    • v.8 no.2
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    • pp.97-107
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    • 1999
  • The osteogenic capacity of the vascularized periosteum autograft has been extensively demonstrated by experimental works. The objective of this study was to characterize the behavior of experimental model of vascularized periosteal flap(VPF) by observing sequential stages of osteogenesis after simulated VPF in rabbits. In experimental group, segmental resection of bone including the periosteum was performed in 22 radii of 22 New Zealand white rabbits preserving the periosteal circulation of median artery to the periosteum. In order to simulate the transplantation of VPF, the vascular pedicle consisting of median artery and veins was dissected from adjacent soft tissue and the periosteum was longitudinally incised to remove the bone followed by repair of the periosteum. From the first to sixteenth week after the simulated VPF, the changes in VPFs were observed by radiological, light microscopical, scanning electron microscopical methods and the activity of osteocalcin was measured by immunohistochemical method. In control group, the bone tissue and periosteum were completely removed from the mid-shaft of radius and the findings were observed by radiological and light microscopical methods. From the results of this study, it is demonstrated that the experimental model of VPF is vigorously and uniformly osteogenic. Therefore it is thought that VPF can be used as a measure to treat bone defect of shaft of long bone.

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Long-term Follow-up of Reconstruction of the Hand with a Temporoparietal Fascial Free Flap (측두두정근막 자유피판술을 이용한 수부재건의 장기추적조사)

  • Yoon, Do-Won;Kim, Jiye;Yang, Eun Jung;Chung, Yoon-Kyu
    • Archives of Reconstructive Microsurgery
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    • v.22 no.1
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    • pp.24-28
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    • 2013
  • Purpose: Soft tissue defect of the hand, which cannot be covered with skin graft or local flap, is usually reconstructed using a free flap. Temporoparietal fascial free flap is one of the best alternatives for functional reconstruction of the hand with exposed tendons, bones, and joints. Materials and Methods: We have experienced four cases of reconstruction using a temporoparietal fascial flap with a skin graft and followed up for 20 years. We conducted a retrospective review of the patients' clinical charts and photos. Results: At the time of initial injury, the average age of patients was 50.3 (39~62) years. The radial artery was used for reconstruction of the dorsal side of the hand, whereas the ulnar artery was used for that of the volar side of the wrist. Short term complication such as skin graft loss and donor site alopecia occurred. However, during the long term follow-up period, no change of flap volume was noted, and full range of motion in the adjacent joint was maintained. In addition, hyperpigmentation of the grafted skin on the flap disappeared gradually. Conclusion: Selection of the optimal flap is important for reconstruction of the hand without functional limitation. We obtained satisfactory soft tissue coverage and functional outcomes using a temporoparietal fascial free flap and followed up for 20 years.

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Current status of and trends in post-mastectomy breast reconstruction in Korea

  • Song, Woo Jin;Kang, Sang Gue;Kim, Eun Key;Song, Seung Yong;Lee, Joon Seok;Lee, Jung Ho;Jin, Ung Sik
    • Archives of Plastic Surgery
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    • v.47 no.2
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    • pp.118-125
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    • 2020
  • Since April 2015, post-mastectomy breast reconstruction has been covered by the Korean National Health Insurance Service (NHIS). The frequency of these procedures has increased very rapidly. We analyzed data obtained from the Big Data Hub of the Health Insurance Review and Assessment Service (HIRA) and determined annual changes in the number of breast reconstruction procedures and related trends in Korea. We evaluated the numbers of mastectomy and breast reconstruction procedures performed between April 2015 and December 2018 using data from the HIRA Big Data Hub. We determined annual changes in the numbers of total, autologous, and implant breast reconstructions after NHIS coverage commenced. Data were analyzed using Microsoft Excel. The post-mastectomy breast reconstruction rate increased from 19.4% in 2015 to 53.4% in 2018. In 2015, implant reconstruction was performed in 1,366 cases and autologous reconstruction in 905 (60.1% and 39.8%, respectively); these figures increased to 3,703 and 1,570 (70.2% and 29.7%, respectively) in 2018. Free tissue transfer and deep inferior epigastric perforator flap creation were the most common autologous reconstruction procedures. For implant-based reconstructions, the rates of directto-implant and tissue-expander breast reconstructions (first stage) were similar in 2018. This study summarizes breast reconstruction trends in Korea after NHIS coverage was expanded in 2015. A significant increase over time in the post-mastectomy breast reconstruction rate was evident, with a trend toward implant-based reconstruction. Analysis of data from the HIRA Big Data Hub can be used to predict breast reconstruction trends and convey precise information to patients and physicians.

Reconstruction of post-burn anterior neck contractures using a butterfly design free anterolateral thigh perforator flap

  • Lellouch, Alexandre G.;Ng, Zhi Yang;Pozzo, Victor;Suffee, Tabrez;Lantieri, Laurent A.
    • Archives of Plastic Surgery
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    • v.47 no.2
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    • pp.194-197
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    • 2020
  • Anterior neck burns represent a major reconstructive challenge due to severe sequalae including restriction in movement and poor aesthetic outcomes. Common treatment options include skin grafting with/without dermal matrices, and loco-regional and distant free flap transfers with/without prior tissue expansion. Such variation in technique is largely influenced by the extent of burn injury requiring resurfacing. In order to optimize like-for-like reconstruction of the anterior neck, use of wide, thin and long flaps such as the anterolateral thigh (ALT) perforator flap have been reported with promising results. Of note, some patients have a tendency towards severe scar contractures, which may be contributed by the greater extent of inflammation during wound healing. We report our experience at 4 years' followup after secondary reconstruction of severe, anterior neck burn contractures in two patients by harvesting the ALT flap with a butterfly design. This technique provides adequate wound resurfacing of the burned neck and surrounding areas, and provides good neck extensibility by addressing both anterior and lateral aspects of the scar defect simultaneously. Such a flap design reduces tension on wound edges and thus, the risk of contracture recurrence in what remains a particularly challenging type of burn reconstruction.

Development of Luteinizing Hormone Releasing Hormone (LHRH) Delivery Systems for Vaginal Mucosal Route

  • Han, Kun;Park, Jeong-Sook;Youn, Bok-Chung;Nam, Joo-Jeong;Park, Hee-Beom;Joseph-R. Robinson
    • Archives of Pharmacal Research
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    • v.18 no.5
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    • pp.325-331
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    • 1995
  • The objective of this study was to find a rational dosage form for vaginal mucosal delivery of LHRH. Vaginal absorption of LHRH was estimated by measuring its ovulation inducting effect in rat and in vitro vaginal membrane permeation study in rabbit. THe effects of different hydrogel bases, such as Polycarbophil and Pemulen compared with solutions on vaginal membrane permeation of LHRH were investigated. Sodium laurate, disodium ethylenediamine brane permeaiton of LHRH were investigated. Sodium ethylenediamine tetraacetate (EDTA) and sodium tauro-24, 25-dihydrofusidate (STDHF), which are effective peptidase inhibitors were chosen as additives to a LHRH hydrogel delivery system and LHRH solutions. A Polycarbophil compared with a solution formulation 3.4 times increase in LHRH vaginal membrane permeability compared with a solution formulation. Vaginal membrane permeability from the Polycarbophil was greater than that from Pemulen hydrogels. This may be due to the larger bioadhesive values. LHRH solution with EDTA(2%), STDHF(1%) and sodlaurate(0.5%) showed 4.1 times, 4.8 times and 6.0 times of ovulation inducing activity compared with control. These results suggest that enzyme inhibition effect of EDTA, STDHF and sod, laurate may be result in substantial enhancement of vaginal absorption. By administraiton of Polycarbophil hydrogels containing LHRH the ovulation inducing activity was 3.3 times greater than the solutions. This result indicates the bioadhesive hydrogels as well as peptidase in hibition significantly improved absorption of LHRH. By coadministration with these inhibitors the ovulation inducing activity of Polycarbophi hydrogel containing LHRH was comparable with subcutaneous administration in ovulation inducing activity.

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Isolation of a Natural Antioxidant, Dehydrozingerone from Zingiber officinale and Synthesis of lts Analogues for Recognition of Effective Antioxidant and Antityrosinase Agents

  • Kuo, Ping-Chung;Damu, Amooru G.;Cherng, Ching-Yuh;Jeng, Jye-Fu;Teng, Che-Ming;Lee, E-Jian;Wu, Tian-Shung
    • Archives of Pharmacal Research
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    • v.28 no.5
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    • pp.518-528
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    • 2005
  • In the present study, the antioxidative and inhibitory activity of Zingiber officinale Rosc. Rhizomes-derived materials (on mushroom tyrosinase) were evaluated. The bioactive co mponents of Z. officinale rhizomes were characterized by spectroscopic analysis as zingerone and dehydrozingerone, which exhibited potent antioxidant and tyrosinase inhibition activities. A series of substituted dehydrozingerones [(E)-4-phenyl-3-buten-2-ones] were prepared in admirable yields by the reaction of appropriate benzaldehydes with acetone and the products were evaluated in terms of variation in the dehydrozingerone structure. The synthetic analogues were examined for their antioxidant and antityrosinase activities to probe the most potent analogue. Compound 26 inhibited Fe$^{2+}$-induced lipid peroxidation in rat brain homogenate with an IC$_{50}$ = 6.3${\pm}$0.4 ${\mu}$M. In the 1,1-diphenyl- 2-picrylhydrazyl (DPPH) radical quencher assay, compounds 2, 7, 17, 26, 28, and 29 showed radical scavenging activity equal to or higher than those of the standard antioxidants, like ${\alpha}$-tocopherol and ascorbic acid. Compound 27 displayed superior inhibition of tyrosinase activity relative to other examined analogues. Compounds 2, 17, and 26 exhibited non-competitive inhibition against oxidation of 3,4- dihydroxyphenylalanine (L-DOPA). From the present study, it was observed that both number and position of hydroxyl groups on aromatic ring and a double bond between C-3 and C-4 played a critical role in exerting the antioxidant and antityrosinase activity.