• The Korean Journal of Pain
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• 제27권3호
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• pp.219-228
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• 2014

Background: A lipo-prostaglandin E1 agonist is effective for the treatment of neurological symptoms of spinal stenosis when administered by an oral or intravenous route. we would like to reveal the therapeutic effect of an epidural injection of lipo-prostaglandin E1 on hyperalgesia in foraminal stenosis. Methods: A total of 40 male Sprague-Dawley rats were included. A small stainless steel rod was inserted into the L5/L6 intervertebral foramen to produce intervertebral foraminal stenosis and chronic compression of the dorsal root ganglia (DRG). The rats were divided into three groups: epidural PGE1 (EP) (n = 15), saline (n = 15), and control (n = 10). In the EP group, $0.15{\mu}g{\cdot}kg-1$ of a lipo-PGE1 agonist was injected daily via an epidural catheter for 10 days from postoperative day 3. In the saline group, saline was injected. Behavioral tests for mechanical hyperalgesia were performed for 3 weeks. Then, the target DRG was analyzed for the degree of chromatolysis, chronic inflammation, and fibrosis in light microscopic images. Results: From the fifth day after lipo-PGE1 agonist injection, the EP group showed significant recovery from mechanical hyperalgesia, which was maintained for 3 weeks (P < 0.05). Microscopic analysis showed much less chromatolysis in the EP group than in the saline or control groups. Conclusions: An epidurally administered lipo-PGE1 agonist relieved neuropathic pain, such as mechanical hyperalgesia, in a rat foraminal stenosis model, with decreasing chromatolysis in target DRG. We suggest that epidurally administered lipo-PGE1 may be a useful therapeutic candidate for patients with spinal stenosis.

• The Korean Journal of Pain
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• 제20권1호
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• pp.15-20
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• 2007

Background: Lipo-prostaglandin E1 (Lipo-$PGE_1$) has vasodilating and platelet aggregation inhibitory characteristics and it has been used as a treatment for patients with blood flow dysfunction disease. Based on the mechanisms of lumbar spinal stenosis, including veno congestion, neuro-ischemia and mechanical compression, we aimed to study whether intravenous Lipo-$PGE_1$ injection has any therapeutic effect on hyperalgesia in a rat foraminal stenosis model. Methods: In this study, twenty male Sprague-Dawley rats were divided into the control (n = 10) and Lipo-$PGE_1$ (n = 10) groups. A small stainless steel rod was inserted into the L5-6 intervertebral foramen to induce intervertebral foramen stenosis and chronic DRG compression. In the Lipo-$PGE_1$ group, $0.15{\mu}g/kg$ of Lipo-$PGE_1$ were injected intravenously via a tail vein for 10 days starting from the $3^{rd}$ day after operation. Behavioral testing for mechanical and thermal hyperalgesia was performed for 3 weeks after the injections. Results: From the $10^{th}$ day after Lipo-$PGE_1$ injection, the rats in the experimental group showed significant recovery of their mechanical threshold, and this effect was maintained for 3 weeks. No significant differences of the thermal hyperalgesia were observed between the two groups. Conclusions: These findings suggest that intravenously injected Lipo-$PGE_1$ may be effective for alleviating neuropathic pain, which isthe main symptom of spinal stenosis, by improving the blood flow dysfunction.

• Archives of Plastic Surgery
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• 제32권1호
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• pp.5-11
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• 2005

Prostaglandin $E_1$($PGE_1$) is known to have various physiological action such as vasodilatation, decrease of blood pressure, angiogenesis, inhibition of platelet aggregation and so forth. $PGE_1$ has been developed in many different formulations in order to overcome its chemical instability and deactivation in the lungs when administered parenterally. Lipo-AS013 is a potent drug with higher chemical stability and greater vascular wall targeting than others. The study was done on $3{\times}10cm$ model flap of dorsal skin of Sprague-Dawley rats and the flap perfusion survival were observed and documented. The flap treated with Lipo-AS013 beforehand was given intravenously Sodium fluorescein 10 minutes later, and then Percent Dye Fluorescence Index(% DFI) was calculated. The results were compared to a control group and the group administered locally epinephrine.. In the control group, the % DFI and flap survival rate increased from $54.1{\pm}6.7$ to $65.0{\pm}2.6$(p<0.01) while in Lipo-AS013 group from $55.3{\pm}2.2$ to $67.4{\pm}1.9$(p<0.01), respectively. In the epinephrine group, the % DFI(p<0.05) and flap survival rate(p<0.001) decreased. In the both epinephrine and Lipo-AS013 group Percent DFI and flap survival rate are comparable with the control group.The result indicates that the potent Lipo-AS013 enhances the blood flow and flap survival. This highly potent Lipo-AS013 may have targeting ability and accumulate $PGE_1$ onto the vascular walls. A quantitative analysis of fluorescence on the skin surface is a reliable tool to measure the blood perfusion into an ischemic flap and its viability. Further comparative study with conventional $PGE_1$ and Lipo-$PGE_1$ is needed in order to clarify the action and efficiency of Lipo-AS013.

• Archives of Plastic Surgery
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• 제32권1호
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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.

• Archives of Plastic Surgery
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• 제37권6호
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• pp.721-725
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• 2010

Purpose: The survival of composite graft is dependent on three steps, (1) plasmatic imbibitions, (2) inosculation, and (3) neovascularization. Among the many trials to increase the survival rate of composite graft, prostaglandin E1 (PGE1) has beneficial effects on the microcirculatory level with vasodilating, antithrombotic, anti-inflammatory and neoangiogenic properties. Lipo-PGE1 which is lipid microspheres containing PGE1 had developed to compensate the systemic and local side effects of PGE1. This study was proposed to determine whether Lipo-PGE1 administration enhanced the survival of composite graft through neovascularization quantitatively in a rabbit ear model. Methods: Fourteen New Zealand White Rabbits each weighing 3~4 kg were divided in two groups: (1) intravenous Lipo-PGE1 injection group and (2) control group. A $2{\times}1\;cm$ sized, full-thickness rectangular composite graft was harvested in each auricle. Then, the graft was reaaproximated in situ using a 5-0 nylon suture. For the experimental group, $3{\mu}g$/kg/day of Lipo-PGE1 ($5{\mu}g$/mL) was administered intravenously through the marginal vein of the ear for 14 days. The control group was received no pharmacologic treatment. On the 14th postoperative day, composite graft of the ear was harvested and immunochemistry staining used Monoclonal mouse anti-CD 31 antibody was performed. Neoangiogenesis was quantified by counting the vessels that showed luminal structures surrounded by the brown color-stained epithelium and counted from 10 random high-power fields (400x) by independent blinded observer. Statistical analysis (Wilcoxon Signed Ranks test for nonparametric data) was performed using SPSS v12.0, with values of p<0.05 considered significant. Results: The mean number of the microvessels was $15.48{\pm}8.65$ in the experimental group and $9.82{\pm}7.25$ in the control group (p=0.028). Conclusion: The use of Lipo-PGE1 facilitated the neoangiogenesis, resulted in the improvement of the survival rate of graft. On the basis of this results, we could support wider application of Lipo-PGE1 for more effective therapeutic angiogenesis and successful survival in various cases of composite graft in the human.

• Archives of Reconstructive Microsurgery
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• 제19권1호
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• pp.46-49
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• 2010

Purpose: It has been reported that the ear perfusion can maintain by a very small pedicle because the ear has good vascularized system. Replantation of an amputated ear with vascular anastmosis, has been reported before and offers the succeessful reconstructive results. But, in this paper we report a case of complete nonmicrosurgical salvage of a nearly amputated ear based on 7 mm-wide small skin pedicle with adjunctive therapies. Methods: A 49-year-old man was referred with a nearly complete detachment of left ear. The blood supply to the ear was maintained exclusively on 7 mm-wide small skin pedicle in the lobule. After we identified the fresh bleeding at the distal margin of the detached ear, we performed the primary repair. At the end of the procedure, the areas of the concha bowl and helical root appeared to be congested. So the immediate postoperative treatment for improving the tissue survival was done with Lipo-Prostaglandin E1 (Eglandin$^{(R)}$) injection, leech apply and antibiotics medications. Results: Assessment of the replanted ear on postoperative day 14 revealed a nearly viable auricle including the helical root. The ear appeared to be entirely healed, with excellent projection and fully restored normal elasticity. Conclusion: We found the complete salvage of a nearly amputated ear based on 7 mm-wide small skin pedicle with adjunctive therapies including Lipo-Prostaglandin E1 (Eglandin$^{(R)}$) injection, leech apply and antibiotics without microsurgery.

• Natural Product Sciences
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• 제10권6호
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• pp.315-320
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• 2004

Alpha-viniferin was previously isolated as a cyclooxygenase (COX)-2 inhibitor from Carex humilis (Cyperaceae) and is an oligomeric stilbene compound with benzofuran (BF) moieties in its chemical structure. In the present study, a chemically synthetic BF compound, named as 3,3-dimethyl-2,3,4,6,7,8,9,10,11,12,13,14,15,16,17,18-hexadecahydro-1H-benzo[b] cyclopentadeca[d]furan-1-one, was discovered to inhibit bacterial lipo polysaccharide (LPS)-induced prostaglandin $E_2$ $(PGE_2)$ production in macrophages RAW 264.7. The BF compound exhibited a selectively preferred inhibitory effect on COX-2 activity over COX-1 activity. Furthermore, BF compound inhibited LPS-induced COX-2 expression at transcription level. As a down-regulatory mechanism of COX-2 expression shown by BF compound, suppression of nuclear factor $(NF)-{\kappa}B$ activation has been demonstrated. BF compound inhibited LPS-induced $NF-{\kappa}B$ transcriptional activity and nuclear translocation of $NF-{\kappa}B$ p65, in parallel, but did not affect LPS-induced degradation of inhibitory ${\kappa}B{\alpha}$ protein $(I{\kappa}B{\alpha})$. Taken together, anti-inflammatory effect of BF compound on $PGE_2$ production was ascribed by its down-regulatory action on LPS-induced COX-2 synthesis in addition to inhibitory action on enzyme activity of COX-2.

• 대한화상학회지
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• 제24권2호
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• pp.21-29
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• 2021

Purpose: Frostbite is a hazard to people exposed to cold environments. With the progression of modern industrial development and change of leisure behavior encountering cold environments, frequent accidental exposure to frostbite injury during work and human behavior is increasing, and the predisposing factors of frostbite were greatly changed than before. The purpose of this study was to make epidemiological analysis, and to review the treatment outcomes of frostbite. Methods: From March 2010 to February 2021, this study has included 27 patients with second- to third-degree frostbite injuries in Advanced Burn Reconstruction Center, Bundang Jesaeng Hosptial. A retrospective study was made about the distribution of age, gender, predisposing factors, prevalent area, type of managements, and the length of treatment period. Results: In our institution, acute management of frostbite patients has included rewarming, anticoagulation therapy (acetylsalicylic acid), and agents to improve vascular perfusion (lipo-prostaglandin E1 [Eglandin^®]). The 25 frostbite patients with second-degree frostbite (92.6%) were successfully managed by the conservative treatment alone with a mean of 20.3 days healing time. Two patients with third-degree frostbite (7.4%) also showed good outcomes after surgical reconstruction with a mean of 59 days healing time. In our clinical experiences of third-degree frostbite, definitive surgical reconstruction should be recommended to wait for more than 4~6 weeks for identification of clear demarcation of necrotic tissue caused by frostbite. In this study, 43 frostbite injuries site in 27 frostbite patients occurred. Among them, 15 patients (55.6%) had multiple-site frostbite injury. The most common predisposing cause of frostbite was refrigerant gas accidents (44.4%), followed by outdoor activity in cold environments (40.8%), misapplying ice pack for treatment purposes (7.4%), barefoot walking on the cold ground (3.7%), and loss of consciousness in cold grounds (3.7%). The most prevalent sites of frostbite injuries revealed as the hand (58.1%), followed by the foot (32.6%), face (7.0%), and abdomen (2.3%). And in the winter season from the November to March, the incidence rate of frostbite injuries was high at 74.1%. Conclusion: This study included 27 frostbite patients with 43 frostbite sites since last decade in a single institution at the community hospital. The frostbite patients with second-degree frostbite (92.6%) were successfully healed by the conservative treatment alone with a mean of 20.3 days healing time. The most common predisposing cause of frostbite was refrigerant gas accidents (44.4%), followed by outdoor activity in cold environments, etc. The most prevalent site of frostbite injuries was the hand (58.1%). And the most prevalent seasonal incidence of frostbite was from November to March (74.1%).