• Archives of Plastic Surgery
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• v.38 no.5
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• pp.567-575
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• 2011

Purpose: Acellular human dermis is very useful implant for use in plastic and reconstructive surgery. However, the volume of acellular human dermis graft is known to decrease for a long time. Basic fibroblast growth factor (bFGF) is a polypeptide that enhances the collagen synthesis and angiogenesis. In the current study we examined whether bFGF could improve the survival of acellular human dermis ($SureDerm^{(R)}$) by increasing angiogenesis of the graft. Methods: Forty rats were divided into two groups (control and bFGF). A 2-mm thick piece of $SureDerm^{(R)}$ was cut into smaller pieces that were $15{\times}5$ mm in size. Two subcutaneous pockets were made on the back of each rat. Grafts sprayed with bFGF were implanted in the bFGF group and injected with bFGF after transplantation every 3 days for 2 weeks. In the control group, the grafts were treated with phosphate-buffered saline (PBS) instead of bFGF. Four days, and 1, 4, and 12 weeks after the implantation, the grafts were harvested and gross and histologic examinations were performed. Inflammation grade, graft thickness, neocollagen density, and neocapillary count were measured. Results: The bFGF group displayed more rapid accumulation of inflammatory cells with a higher density of neocapillaries, and increased active collagen synthesis. After 12 weeks, the thickness of the grafts in the control and bFGF groups was $75.15{\pm}4.80%$ and $81.79{\pm}5.72%$, respectively, in comparison to the thickness before transplantation. There was a statistically significant difference between both groups ($p$ <0.05). Conclusion: bFGF was effective in reducing the absorption of acellular human dermal grafts by increasing angiogenesis and accelerating engraftment. In conclusion, bFGF may be a good tool for use in acellular human dermal graft transplantation for reconstructive surgery involving soft-tissue defects.

• Journal of Soil and Groundwater Environment
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• v.28 no.6
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• pp.33-44
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• 2023

A risk assessment on the heavy metals including arsenic (As), cupper (Cu), lead (Pb), and zinc (Zn) was investigated by setting exposure routes in agricultural fields. Moreover, the factors requiring improvement in risk assessment were also discussed through a review of the dermal absorption slope factor (SF_abs) and total amount of suspended particles (TSP) in the current risk assessment guidelines. Assessment results show that the total cancer risk (TCR) of As through crop and soil ingestion was 1.51E-03 in adults and 6.37E-4 in children, which indicated a carcinogenic risk (exceeding 1E-05). On the other side, the harzard index (HI) was 3.37 in adults and 1.41 in children, which was evaluated as having a non-carcinogenic risk (>1). The carcinogenic purification targets for As were calculated to be 6.84 mg/kg in adults and 6.86 mg/kg in children, while the non-carcinogenic purification targets were calculated to be 13.43 mg/kg for adults and 22.54 mg/kg for children. When applying SF_abs 61 of the current guidelines, it appears that there is a carcinogenic risk even though the As exposure concentration is below the area of concern 1 standard (25 mg/kg), which suggestes that additional research on this factor is required for the risk assessment. In order to apply the measured suspended particle concentration to risk assessment, TSP should be derived from PM10 using an appropriate correlation equation. As a result, it is suggested to improve the risk assessment guidelines so that the mesured PM10 value measured in the field can be used directly.

• Journal of The Korean Society of Clinical Toxicology
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• v.2 no.2
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• pp.101-105
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• 2004

Purpose: Paraquat is the most commonly used herbicide in Korea. Exposure to paraquat through the skin has resulted in local irritation or inflammation of varying degree, sometimes severe. The purpose of this study was to review the patients with paraquat poisoning by skin absorption. Methods: We analysed retrospectively the clinical and laboratory findings of 45 patients with paraquat poisoning after dermal exposure, who were admitted to Soonchunhyang University Cheonan Hospital from January 1999 to December 2003. Results: Among 870 cases of paraquat poisoning, 45 cases were exposed to paraquat through the skin. The peak incidence was the fifth decade($40\%$). The clinical symptoms were pain, pruritus, nausea, and vomiting. The major skin lesions were generalized vesicobullae and necrotic erosion in face, scrotum, trunk, upper and lower extremities and etc. All patients were survived after skin contact or inhalation of paraquat. Conclusion: This study illustrates the extreme toxicity of paraquat and demonstrates that lethal quantities of paraquat may be absorbed if repeated exposure to it. Stricter precautions, including the mandatory use of protective clothing, should be recommended whenever this material is used.

• Toxicological Research
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• v.17 no.4
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• pp.317-323
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• 2001

The skin penetration rate of methidathion in vitro and pharmacokinetics of methidathion in vivo were studied with male Sprague-Dawley rats by dermal treatment. The in vitro skin penetration rates for Sprague-Dawley rats of methidathion technical (50 mg, 100 ${mu}ell$) and emulsifable concentrate (EC,40mg, 100${mu}ell$) were determined as 18.4 $\mu\textrm{g}$/c $m^2$/h (RSD : 6.5) and 18.5 $\mu\textrm{g}$/c $m^2$/h (RSD : 3.2), respectively. Dose-related systemic exposure (AUC) was observed in rats after dermal treatment. The corresponding AUC, $T_{max}$, $C_{max}$, and $T_{1}$2/ of methidathion in plasma were 1.5$\mu\textrm{g}$.hr/ml, 6 h, 0.10 $\mu\textrm{g}$/ml, and 16 h, for 116mg/kg doses, 3.2 $\mu\textrm{g}$. hr/ml, 8 h, 0.12 $\mu\textrm{g}$/ml, and 23 h, for 232 mg/kg doses and 10 $\mu\textrm{g}$. hr/ml, 12 h, 0.32 $\mu\textrm{g}$/ml, and 20 h, for 1,160 mg/kg doses respectively. The urinary excretion of methidathion, estimated wing an equation derived from the in vitro skin penetration study was 0.24~0.35% of the absorbed dose. The concentration of methidathion in kidney was higher than that in liver. Dose-dependent absorption and excretion of methidathion without saturation was observed under in vivo experimental condition.n.n.

• YAKHAK HOEJI
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• v.41 no.6
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• pp.737-748
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• 1997

Distribution of rhEGF in the skin, plasma and several organ tissues following topical application of $^{125}I-rhEGF$ (0.4${\mu}$Ci) solution in 25% Pluronic F-127 on 154$mm^2$ normal and damaged (burned and stripped) skins of hairless mice was examined. The radioactivity in the stripped skin tissues increased as a function of time, and was 10-20 times higher than that in the normal and burned skins. The fractions of intact drug in the skin tissues were 40-60% for the normal and burned skins, and 60-80% for the stripped skin. It indicates that the stratum corneum layer behaves as a barrier for the dermal penetration of the drug. The radioactivity in the plasma was much higher for the stripped skin than for the normal and burned skins. However, the concentration of intact drug in the stripped skin was comparable to those in the normal and burned skins indicating most severe degradation (or metabolism) of the drug in the stripped skin. As a result, the fraction of intact drug in the plasma was lowest for the stripped skin (<10%). Body organ distribution of the drug was much higher for the stripped skin. The concentration in the stomach. Both in total radioactivity and intact drug, showed more than 10-times higher value than in the other organs (liver, kidney and spleen). The fraction of intact drug in each organ tissue was below 10-20%. And generally lowest for the stripped skin. The lowest fraction of the drug for the stripped skin could not be explained by the activity of the aminopeptidases in the skin since it was lower for the stripped skin than for the normal skin. Thereover, the fraction of intact drug appears to be determined by the balance between dermal uptake and systemic elimination of the drug, for example. The mechanism of dermal uptake of rhEGF was examined by topical applying 200${\mu}$l of 25% Pluronic F-127 solution containing 0.4 ${\mu}$Ci of $^{125}I-rhEGF$ and 0.14${\mu}$Ci of $^{14}C$-inulin (a marker of passive diffusion). The radioactivity of $^{125}I-rhEGF$ at each sampling time point (0.5, 1, 2, 4 and 8hr) was correlated (p<0.05) with the corresponding radioactivity of $^{14}C$-inulin. It appears to indicate the rhEGF may be uptaken into the skins mainly by the passive diffusion. This hypothesis was supported by the constant specific binding of EGF to the skin homogenates regardless of the skin models. Receptor mediated endocytosis (RME) appears to contribute negligibly, if any, to the overall uptake process.

• Toxicological Research
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• v.17 no.1
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• pp.7-9
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• 2001

The quantitative assessment of the penetration of organic solvents through skin is necessary for the evaluation of health hazards in occupational environments. We investigated the rate of dermal penetration when mixed or single forms of organic solvents were placed into a diffusion cell in vitro or into an experimental animal in vivo. The diffusion rates of methanol. toluene, and styrene were 6.07, 0.129, and 0.046 mg/$cm^2$/h, respectively. When skin was exposed to the mixed solvent of methanol and toluene, the penetration rate of toluene did not change significantly (0.110 mg/$cm^2$/h). However, the rate of methanol penetration increased to 43.90 mg/$\textrm{cm}^2$/h. The penetration rate of methanol also increased significantly to 54.69 mg/$cm^2$/h by mixing it with styrene. The concentration of methanol in the blood was monitored during the epicutaneous exposure in rats. The blood concentration of methanol was increased by mixing methanol with toluene as seen in the in vitro experiments. These results showed that the penetration rate of organic solvents would be enhanced by mixing them with other solvents.

• Biomolecules & Therapeutics
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• v.9 no.4
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• pp.298-306
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• 2001

To develop a novel transdermal delivery system of loxoprofen (LP), a potent antiinflammatory and analgesic agent, the effects of vehicle composition and drug loading dose on the skin permeation property were investigated. And in vivo skin absorption property studied by analysing the $C_{max}$ and AUC was investigated after applying the developed plaster systems on rabbit back skin. Addition of isopropyl myristate (IPM) and IPM-diethylene glycol monoethyl ether (DGME) cosolvent in the plaster showed higher permeation rates than those from propylene glycol laurate-DGME cosolvent systems. As the concentration of LP in the plaster increased from 0.56 mg/$\textrm{cm}^2$ to 1.19 mg/$\textrm{cm}^2$, the drug release and skin permeation rates increased linearly. At loading dose of 1.19 mg/$\textrm{cm}^2$, the flux reached 35.6 $\mu$g/$\textrm{cm}^2$/hr. New LP plasters showed a good adhesive property onto skin, and showed no crystal formation. The AU $C_{0-24hr}$ and $C_{max}$ after dermal application of LP plaster (60 mg/70 $\textrm{cm}^2$) were found to be 6951$\pm$230 ng.hr/ml and 400$\pm$44 ng/ml, respectively. And the plasma concentration maintained above 300 ng/ml up to 24 hr period. In the carrageenan-induced rat paw edema test, LP plaster showed similar inhibition rate with marketed ketoprofen (Ketoto $p^{R}$) plaster.aster.r.

• Archives of Pharmacal Research
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• v.24 no.6
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• pp.572-577
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• 2001

The feasibility of skin penetration was studied for aspalatone (AM, acetylsalicylic acid maltol ester), a novel antithrombotic agent. In this studys hairless mouse dorsal skins were used as a model to select composition of vehicle and AM. Based on measurements of solubility and partition coefficient, the concentration of PC that showed the highest flux for AM across the hairless mouse skin was found to be 40%. The cumulative amount permeated at 48 h, however, appear inadequate, even when the PC concentration was employed. To identify a suitable absorption enhancer and its optimal concentration for AM, a number of absorption enhancers and a variety of concentration were screened for the increase in transdermal flux of AM. Amongst these, linoleic acid (LOA) at the concentration of 5% was found to have the largest enhancement factor (i.e., 132). However, a further increase in AM flux was not found in the fatty acid concentration greater than 5%, indicating the enhancement effect is in a bell-shaped currie. In a study of the effect of AM concentration on the permeation, there was no difference in the permeation rate between 0.5 and 1% for AM, below its saturated concentration. At the donor concentration of 2%, over the saturated condition, the flux of AM was markedly increased. A considerable degradation of AM was found during permeation studies, and the extent was correlated with protein concentrations in the epidermal and serosal extracts, and skin homogenates. In rat dorsal skins, the protein concentration decreased in the rank order of skin homogenate > serosal extract > epidermal extract. Estimated first order degradation rate constants were $6.15{\pm}0.14,{\;}0.57{\pm}0.02{\;}and{\;}0.011{\pm}{\;}0.004{\;}h^{-1}$ for skin homogenate, serosal extract and epidermal extract, respectively. Therefore, it appeared that AM was hydrolyzed to some extent into salicylmaltol by esterases in the dermal and subcutaneous tissues of skin. taken together, our data indicated that transdermal delivery of AM is feasible when the combination of PC and LOA is used as a vehicle. However, since AM is not metabolically stable, acceptable degradation inhibitors may be nervessary to fully realize the transdermal delivery of the drug.

• Archives of Plastic Surgery
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• v.45 no.6
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• pp.564-571
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• 2018

Background Chronic wounds occur due to failure of the normal healing process, associated with a lack of deposition of cellular components and a suitable microenvironment such as the extracellular matrix (ECM). Acellular dermal matrix (ADM) is viewed as an ECM substitute, and a paste-type ADM has recently been introduced. We hypothesized that CGPaste, an injectable paste-type ADM, could serve as a scaffold and promote wound healing. Methods We retrospectively studied seven patients in whom CGPaste was applied between 2017 and 2018, who had pressure ulcers, necrotizing fasciitis, diabetic foot ulcers, traumatic defects, and osteomyelitis. The goal of applying CGPaste was to achieve complete wound healing with re-epithelialization or growth of granulation tissue, depending upon the wound bed status. CGPaste was injected based on the wound size along with the application of a dressing. Results Four of the seven patients showed granulation tissue on their wound bed, while the other three patients had a bony wound bed. The mean wound area was $453.57mm^2$ and the depth was 10.71 mm. Wound healing occurred in five of the seven patients (71.43%). The mean duration of complete healing was 2.4 weeks. Two patients showed failure due to paste absorption (29.57%); these patients had wound beds comprising bone with relatively large and deep wounds ($40{\times}30$ and $30{\times}20mm^2$ in area and 15 and 10 mm in depth). Conclusions CGPaste is an effective option for coverage of small and deep chronic wounds for which a flap operation or skin grafting is unfeasible.

• Archives of Plastic Surgery
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• v.45 no.6
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• pp.504-511
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• 2018

Background Acellular dermal matrix (ADM) helps wound healing by stimulating angiogenesis, acting as a chemoattractant for endothelial cells, providing growth factors, and permitting a substrate for fibroblasts to attach. The current standard for using paste-type ADM (CG Paste) in wound healing is direct application over the wounds. The major concerns regarding this method are unpredictable separation from the wounds and absorption into negative-pressure wound therapy devices. This study aimed to investigate the effects of subcutaneous injection of paste-type ADM on wound healing in rats. Methods Full-thickness skin defects were created on the dorsal skin of rats. Eighteen rats were randomly divided into three groups and treated using different wound coverage methods: group A, with a saline dressing; group B, standard application of CG Paste; and group C, injection of CG Paste. On postoperative days 3, 5, 7, 10, and 14, the wound areas were analyzed morphologically. Histological and immunohistochemical tissue analyses were performed on postoperative days 3 and 7. Results Groups B and C had significantly less raw surface than group A on postoperative days 10 and 14. Collagen fiber deposition and microvessel density were significantly higher in group C than in groups A and B on postoperative days 3 and 7. Conclusions This study showed comparable effectiveness between subcutaneous injection and the conventional dressing method of paste-type ADM. Moreover, the injection of CG Paste led to improved wound healing quality through the accumulation of collagen fibers and an increase in microvessel density.