• BMB Reports
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• 제48권3호
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• pp.153-158
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• 2015

As FK506 binding proteins (FK506BPs) are known to play an important role in the regulation of a variety of biological processes related to cell survival, this study was designed to examined the protective effects of FK506 binding protein 12 (FK506BP) on low humidity air flow induced dry eye in a rat model using transduced PEP-1-FK506BP. After the topical application of PEP-1-FK506BP, tear volumes were markedly increased and significant prevention of cornea damage was observed compared with dry eye rats. Further, immunohistochemical analysis demonstrated that PEP-1-FK506BP markedly prevented damage to the cornea, the bulbar conjunctiva, and the palpebral conjunctiva epithelial lining compared with dry eye rats. In addition, caspase-3 and PARP expression levels were found to be decreased. These results demonstrated that topical application of PEP-1-FK506BP significantly ameliorates dry eye injury in an animal model. Thus, we suggest that PEP-1-FK506BP can be developed as a new ophthalmic drop to treat dry eye diseases.

• 대한예방한의학회지
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• 제18권2호
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• pp.89-100
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• 2014

Objective : The co-administration effects of Gongjindan (GJD) on the pharmacokinetics (PK) of sorafenib were observed as a process of the comprehensive and integrative medicine. Methods : After sorafenib treatment, GJD was administered within 5 min. The plasma were collected at 30min before administration, 30min, 1, 2, 3, 4, 6, 8 and 24hrs after end of GJD treatment, and plasma concentrations of sorafenib were analyzed using LC-MS/MS methods. PK parameters of sorafenib ($T_{max}$, $C_{max}$, AUC, $t_{1/2}$ and $MRT_{inf}$) were analysis as compared with sorafenib single administered rats. Results : The absorption of sorafenib were significantly increased at 30min, 1, 6 and 6hrs after co-administration with GJD as compared with sorafenib single treated rats. Accordingly, the $AUC_{0-t}$ (47.20%) of sorafenib was significantly increased but $t_{1/2}$ (-30.63%) and $MRT_{inf}$ (-34.11%) in co-administered rats were non-significantly decreased. These findings are considered as direct evidences that GJD increased the oral bioavailability of sorafenib through increase of the absorption, when they co-administered within 5min. Conclusion : Based on the results, co-administration of GJD increased the oral bioavailability of sorafenib through increase of the gastrointestinal absorption. It is considered that the more detail pharmacokinetic studies should be tested to conclude the effects of GJD on the pharmacokinetics of sorafenib, when they were co-administered, like the effects after co-administration with reasonable intervals considering the $T_{max}$ of sorafenib (about 3.5hr-intervals) and after repeated co-administrations.Hence, concomitant uses of GJD with sorafenib may require close monitoring for potential drug interactions.

• 동의생리병리학회지
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• 제29권4호
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• pp.330-336
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• 2015

Polycan originating from Aureobasidium pullulans is mostly composed of β-1, 3/1, 6 glucans and possesses an anti-osteoporotic effect. We conducted a randomized, double-blind, placebo-controlled trial to examine the efficacy and safety of the polycan on bone biochemical markers in healthy perimenopausal women. Sixty subjects were randomly allocated to 2 groups-group 1 received 400 mg of polycan and group 2 received placebo-these were administered once daily for 28 days. Fasting blood and urine samples were collected at baseline and 4 weeks after treatment. The primary outcome was change in osteocalcin (OSC) and bone-specific alkaline phosphatase (BALP). Changes in calcium (Ca), phosphorus (P), C-telopeptide of collagen cross-links (CTx), N-telopeptide of collagen cross-links (NTx), and deoxypyridinoline (DPYR) were the secondary outcomes. A safety assessment was performed using adverse event (AE) and laboratory data. After 4 weeks of polycan treatment, OSC, DPYR, and BALP levels changed (P < 0.05) significantly from baseline in both groups. However, no significant differences were observed in any markers between the 2 groups, except for P (P < 0.05). Interestingly, group 2 showed a significant increase in CTx (65.2%, P < 0.05), while CTx in group 1 slightly increased (17.2%). Both groups showed no significant differences in AE. Although 4 weeks of polycan treatment did not have a statistically significant effect on bone metabolism biomarkers, increases in CTx were modestly inhibited by polycan. Further studies in a large population and longer treatment periods are needed to confirm the effect of polycan on bone turnover.

• 대한예방한의학회지
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• 제20권2호
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• pp.97-109
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• 2016

Objectives : The effects of Jaeumkanghwatang (JEKHT) co-administration on the pharmacokinetics of tamoxifen were observed after oral combination treatment of tamoxifen 50 mg/kg with JEKHT 100 mg/kg on JEKHT 6-day repeated oral pretreated rats with 8-day repeated co-administration to confirm the effects of JEKHT co-administration on the pharmacokinetics of tamoxifen. Methods : Six days after pretreatment of JEKHT 100 mg/kg, tamoxifen 50 mg/kg was co-administered with JEKHT 100 mg/kg, once a day for 8 days within 5 min. The blood were collected at 30 min before administration, 30 min, 1, 2, 3, 4, 6, 8 and 24 hrs after end of first and last 8th tamoxifen treatment, and plasma concentrations of tamoxifen were analyzed using LC-MS/MS methods. PK parameters of tamoxifen ($T_{max}$, $C_{max}$, AUC, $t_{1/2}$ and $MRT_{inf}$) were analysis as compared with tamoxifen single administered. Results : Six-day repeated oral pretreatment of JEKHT and 8-day repeated oral co-administration of tamoxifen within 5 min did not influenced on the plasma concentrations and pharmacokinetic parameters of tamoxifen, oral bioavailability, as compared with tamoxifen single treated rats, except for some negligible effects. Conclusions : It is concluded that JEKHT did not influenced on the plasma concentrations and pharmacokinetic parameters, the oral bioavailability of tamoxifen. Therefore, it is considered that co-administration of JEKHT and tamoxifen will be provide an effective novel treatment regimen on the comprehensive and integrative medicine for breast cancer patients, if they showed favorable synergic effects on the pharmacodynamics or reduce the tamoxifen treatment related toxicity and side effects in future studies.

• 대한예방한의학회지
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• 제17권2호
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• pp.139-155
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• 2013

Purpose : This study was aim to evaluate effects of pharmacodynamics and toxicity in combination therapy of donepezil with Gongjindan. The effects of Gongjindan co-administration on the pharmacokinetics (PK) of donepezil were observed after single and 7-day repeated oral co-administration with 1.5hr-intervals, to evaluate synergic pharmacodynamics and reduce toxicity of combination therapy of donepezil with Gongjindan. Materials and Methods : After 10mg/kg of donepezil treatment, Gongjindan100mg/kg was administered with 1.5hr-intervals. The plasma were collected at 30min before administration, 30min, 1, 2, 3, 4, 6, 8 and 24hrs after end of first and last 7th donepezil treatment, and plasma concentrations of donepezil were analyzed using LC-MS/MS methods. Results : Gongjindan markedly inhibited the absorption of donepezilregardless of sample time, from 30min to 8hrs after end of first 1.5hr-interval co-administration as compared with donepezil single treated rats. Especially the absorption of donepezil was significantly decreased at 2, 4, 6 and 8hrs after co-administration as compared with donepezilsingle treated rats. Accordingly, the Cmax (-26.236%), $AUC_{0-t}$(-26.02%) and $AUC_{0-inf}$(-25.90%) of donepezil in 1.5hr-interval co-administered rats were dramatically decreased as compared with donepezilsingle treated rats, respectively. However, no meaningful changes on the plasma donepezil concentrations and pharmacokinetic parameters were detected after end of last 7th 1.5hr-interval co-administration as compared with donerezil single treated rats, except for non-significant slight increases of Tmax(16.67%) detected in co-administered rats as compared with donepezil single treated rats. Conclusion : These findings are considered as direct evidences that Gongjindan also decreased oral bioavailability of donerezil as inhibited the absorptions, when they were co-administered with 1.5hr-intervals, but they may be adapted after 7 days continuous repeated l.5hr-interval co-administration.

• The Korean Journal of Physiology
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• 제26권2호
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• pp.143-150
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• 1992

The purpose of this study is to obtain the effective concentration of capsaicin to relieve pain with no change in the number of C-fibers and its effective duration for pain relief. Capsaicin has been used extremely as a experimental tool and as topical medications for acute or chronic tissue injuries and partial nerve injury is the main cause of causalgiform pain disorders in humans. Here, the left sciatic nerve was ligated unilaterally at the high level of the thigh to prepare an animal model of this pain condition. The rat developed guarding behavior of the ipsilateral hind paw within a few hours after the operation and this behavior was maintained for several months thereafter, suggesting the possibility of spontaneous pain. These animals were divided into two groups(4-week & 8-week) and each group was subdivided into five groups by different concentration (0.05, 0.1, 0.5, 1.0 & 2.0%). Each capsaicin concentration was treated locally on the spinal cord-side of the ligated nerve and the foot withdrawal latency was measured. Thereafter, the dorsal roots of L5 were removed from both sides immediately after in tracardial perfusion for the counting of C-fibers by the histological procedure. There were no significant differences in the foot-withdrawal latency and the number of C-fibers between the left side treated with 0.05% capsaicin and the right side treated with the vehicle. However, latencies of the left sides treated with 0.1, 0.5, and 1.0% capsaicin increased significantly throughout 4-6 weeks with almost no change in the number of C-fibers, and the latencies showed the trends to approach slowly to those of the conditions after operation. The latency of subgroup treated with 2.0% increased by approximate 10% more than that of the right side throughout 8 weeks, and the number of C-fibers decreased by about 30% or more These results suggest that the elevated latency with capsaicin(0.1-1.0%) treatment is due to the inhibition of impulse transmission throughout the primary afferent fiber and the data from 2.0% are due to partial destruction of C-fibers. Therefore, capsaicin concentrations from 0.1% to 1.0% are probably very effective for the treatment of causalgiform pain with almost no destruction of C-fibers.

• 동의생리병리학회지
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• 제36권4호
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• pp.125-129
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• 2022

The purpose of study is to evaluate in vitro anti-oxidant and anti-inflammatory effects of Moringa Folium and Eucommiae Cortex 2:1 (g/g) mixtures (MEMix). HaCaT and human normal dermal fibroblast were treated with 0.01-1 mg/mL of MEMix to monitor cytotoxicity. Radical scavenging activities of MEMix were examined by DPPH assay. To explore anti-inflammatory effect, Raw 264.7 cells were pretreated with MEMix for 1h and subsequently exposed to LPS for 18h. NO release and cytotoxicity of Raw 264.7 cells were measured by adding Griess and MTT reagents, respectively. TNF-α, IL-1β, IL-6, and PGE2 productions were examined by ELISA. Immunoblot analysis was conducted to examine COX-2 expression in MEMix pretreated Raw 264.7 cells. Up to 1 mg/mL concentration, treatment of MEMix for 24 h did not affect normal dermal fibroblast viability and significantly reduced cell viability of HaCaT cells with no concentration dependency. MEMix increased DPPH radical scavenging activity with concentration dependency. Radical scavenging activities by 1 mg/mL of MEMix was comparable with 30 µM of trolox. Pretreatment of MEMix did not change the reduction of Raw 264.7 cell viability. Exposure of LPS in Raw 264.7 cells significantly increased NO, TNF-α, IL-1β, IL-6, and PGE2 productions, and MEMix pretreatment attenuated these productions by LPS concentration dependently. However, pretreatment with MEMix did not change COX-2 expression by LPS in Raw 264.7 cells. MEMix showed in vitro anti-oxidant and anti-inflammatory activities. MEMix would be useful candidate agent against inflammation.

• 한방안이비인후피부과학회지
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• 제35권4호
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• pp.63-74
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• 2022

Objectives : Skin aging is generally characterized by wrinkles, sagging, loss of elasticity roughness, pigmentation and dryness. This changes is caused by reducing the elements constituting the extracellular matrix contributing to the physiological properties of the skin, such as collagen fiber, elastic fiber, and hyaluronic acid. Adequate skin hydration is important to maintain normal skin function and reduce skin aging. The present study is objective to observe skin moisturizing effects of Unripe apple(UA, Immature fruit of Malus pumila Mill) in vivo and its underlying molecular mechanisms. Methods : ICR mice were orally administerd UA(100, 200 and 400mg/kg/day) for 8 weeks, and skin water contents and the expression of transforming growth factor (TGF)-𝛽1, ceramide, hyaluronan and collagen type I(COL1) were measured in dorsal back skin of the mice. Gene expression of hyaluronan synthase(HAS1, HAS2, HAS3), collagen synthase(COL1A1, COL1A2) and TGF-𝛽1 were also determined by realtime RT-PCR. Results : Skin water contents and the expression of TGF-𝛽1, ceramide, COL1 and hyaluronan were significantly increased in UA group(100, 200 and 400mg/kg/day) compared to vehicle control. The mRNA expression of HAS isoform(HAS1, HAS2, HAS3), COL1A1, COL1A2, and TGF-𝛽1 were also significantly increased by UA. Conclusions : UA has skin moisturizing effects and enhancement activities in skin function related components(COL1, hyaluronan, ceramide and TGF-𝛽1). These results suggested that UA can be a developing candidate for developing alternative skin protective agent or functional food ingredient.

• 한국임상수의학회지
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• 제40권2호
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• pp.93-103
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• 2023

The tendon is a dense connective tissue that connects muscle to bone and plays an essential role in joint motion. The injured tendon heals slowly owing to its low cellularity and vascularity. This study aimed to evaluate and compare the effects of regenerative injection therapy (RIT), 20 % dextrose prolotherapy (DP), and platelet-rich plasma (PRP) injections that can promote tendon healing. Twenty-one New Zealand white rabbits were divided into the control, DP, and PRP treatment groups. The superficial digital flexor tendon (SDFT) of the right hindlimb of each rabbit was used. A round defect of 2 mm was induced. Approximately 0.2 mL of 20% dextrose and autologous PRP were injected into the proximal and distal ends of the SDFT mass. Radiographic and ultrasonographic examination and cross-sectional area (CSA) calculations were performed pre-operatively and at 2, 4, and 8 weeks. The SDFT of both limbs was transected for biomechanical and histomorphometric evaluations. The SDFT of the left limb was transected for intact control. Semi-quantitative analysis was performed to evaluate the histomorphometric properties. Additional analysis was performed using H&E, Masson's trichrome, and immunohistochemical staining. The biomechanical evaluation showed that the treatment groups had higher tensile strength compared to the defect control group, while the PRP group had higher tensile strength than the DP group. On histological examination, the treatment groups appeared to be relatively closer to the remodeling phase of the healing process than the defect control group; the characteristics of the PRP group were closer to the remodeling phase than those of the DP group. The ultrasonographic examination showed different tendencies. Increased values in the CSA were observed during the early period in the treatment groups. This study suggests that PRP and DP can promote the healing of tendon injury, and these effects were superior with PRP than that with DP.

• 대한수의학회지
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• 제39권5호
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• pp.908-920
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• 1999

We investigated the cytogenetic characteristics of Korean native goat(Capra hircus). Chromosome slides were prepared from peripheral blood cell cultures. GTG, GBG, RBG and CBG-banding techniques were employed on those slides. The high resolution karyotype of Korean native goat could be made with the incorporation of BrdU. Korean native goat has 60 chromosomes composed of 58 autosomes and XY or XX sex chromosomes. All of autosomes of Korean native goat were acrocentric chromosomes. X chromosome was submetacentric and Y chromosome was metacentric. The GTG, GBG and RBG-band patterns of Korean native goat were similar to those of other goats. CBG-band regions were distinct at the proximal portion of the long arms of all autosomes in Korean native goats. According to our investigation, there was no significant difference in chromosomal band patterns between Korean native goat and other goats. It might be necessary to use molecular genetic markers for clarifying the genetical characteristics of Korean native goat whose biological characteristics are not clearly defined.