• Journal of Pharmaceutical Investigation
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• 제35권5호
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• pp.375-381
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• 2005

A rapid and specific high-performance liquid chromatographic method was developed and validated for the simultaneous determination of prostaglandin $E_{1}\;(PGE_{1})$ and prostaglandin $E_{1}$ ethyl ester $(PGE_{1}-EE)$ in hairless mouse skin homogenate. The sample treatment procedure involved deproteination and precipitation by acetonitrile. $PGE_{1}$ and $PGE_{1}-EE$ in supernatant were separated in a reversed-phase C18 column without being interfered by other components present in hairless mouse skin homogenate. 9-Anthracenecarboxylic acid was used as an internal standard. The retention times of $PGE_{1}$, 9-anthracenecarboxylic acid and $PGE_{1}-EE$ were, 4.5, 9.5 and 18.0 min, respectively. The assay showed linearity from 1 to $40\;{\mu}g/ml$ for both $PGE_{1}$ and $PGE_{1}-EE$. Precision expressed as RSD ranged from 2.3 to 14.1 % for $PGE_{1}$ and 1.6 to 11.0% for $PGE_{1}-EE$. Accuracy ranged from 100.5 to 119.6 % for $PGE_{1}$ and from 98.0 to 103.7% for $PGE_{1}-EE$. This method was employed successfully to follow the time course of concentrations of $PGE_{1}$ and $PGE_{1}-EE$ in hairless mouse skin homogenate for stability study.

• Journal of Pharmaceutical Investigation
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• 제34권2호
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• pp.107-114
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• 2004

External lyogels containing prostaglandin $E_1$ ethyl ester $(PGE_1-EE)$, a prodrug of prostaglandin $E_1\;(PGE_1)$ as a therapeutic agent for erectile dysfunction, were formulated to overcome the aqueous instability and enhance the percutaneous absorption. Lyogels of $PGE_1-EE$ were prepared with ethanol (EtOH)/proplyene glycol (PG) cosolvent system as a vehicle, cineol as an enhancer, and hydroxypropylcellusose as a gelling agent. In vitro percutaneous absorption studies were performed to determine the rate of $PGE_1$ absorption through rat or hairless mouse skin. The permeability of $PGE_1-EE$ lyogel with enhancer was 16-fold greater than that of lyogel without enhancer. Cosolvent produced 9-fold increase in percutaneous absorption. Pharmacodynamic effects of lyogels were evaluated in mature male cats in terms of intracavernosal pressure (ICP). Lyogels containing 0.1 % of $PGE_1-EE$ showed higher ICP compared to intraurethral preparation of $PGE_1$ (1 %) and enhancer-free control lyogel. The shelf-life $(t_{10%})$ of lyogel at refrigerated condition $(4^{\circ}C)$ was calculated as 928 days, which is 4.2 times longer than that of control hydrogel. As a result, $PGE_1-EE$ was formulated successfully to a lyogel system with a selective enhancer and cosolvent system for the topical delivery of $PGE_1$.

• 대한약리학회지
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• 제11권2호
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• pp.41-46
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• 1975

The isolated strips of tortoise intestine are evaluated as a test organ for bioassay of prostaglandin $E_1$. This preparation responded highly sensitively to $PGE_1$ and $PGE_2$ in picogram concentration range. The mean slope and the value of precision index among the doses of 0.1, 0.3 and 0.5ng/ml in final concentration were 37.7 and 0.143, respectively. And this was relatively insensitive to different prostaglandins; $E_1/E_2{\gtrsim}1$, $E_1/A_2{\sim}50$ and $E_1/F_{2\alpha}{\sim}100$, and showed the dual responses to 5-hydroxytryptamine and histamine; initial contraction followed by relaxation. The dose-ratio inducing the relative equal contraction height for $PGE_1$, acetylcholine, caerulein, angiotensin and barium chloride was 0.4 : 50 : 25 : 10 : 100 in this order. These results suggest that the intestinal strips of the tortoise are suitable for bioassay of prostaglandin $E_1$ and $E_2$ between the doses of 0.1 and 1.0 ng/ml level in the tissue extracts.

• The Korean Journal of Pain
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• 제7권2호
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• pp.299-302
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• 1994

Prostaglandin E1(PGE1) is a potent vasodilator and is a useful drug for the treatment of occlusive peripheral vascular disease. It has been used systemically via intravenous route or regionally via intraarterial route. We tried intravenous regional administration of PGE1 for the treatment of a patient with occlusive arterial disease involving left fingers. During the 13th injection, the patient complained of severe pain at the injection site during the drug administration. Thereafter, the patient developed painful and severe swelling with blebs on his left hand. Systemic antibiotics were given together with stellate ganglion block of the affected left side. PGE1 was substituted to reserpine, which is subcutaneously injectable, for the second term treatment.

• Archives of Reconstructive Microsurgery
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• 제9권2호
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• pp.190-198
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• 2000

본 연구는 백서 복직근피판에 있어 허혈-재혈류 손상에 미치는 prostaglandin E1(PGE-1)의 예방효과를 분석 실험하였으며, 그 기전으로 내피세포의 intercellular adhesion molecule-1(ICAM-1)이 down regulation 됨을 확인하였다. 기존의 PGE-1은 혈관 확장 및 혈소판 응고 저하 등의 기전으로 피판 이식술 후 주로 사용하였으나, 허혈-재혈류 손상 시에 PGE-1 역할에 대한 연구는 잘 알려진바 없다. 허혈-재혈류 손상에 대한 기전은 현재 여러 가설로 설명되고 있으나, 최근 내피 세포와 백혈구의 역할이 주목을 받고 있다. 장시간 허혈 상태의 피판은 재혈류시 백혈구가 내피세포에 접착함으로써 직간접적인 경로로 독소를 생성하며, 결국 내피세포 및 주변조직의 괴사로 이어진다. 본 연구는 면역조직학 염색을 통한 내피세포의 ICAM-1 발현 억제와 그로 인한 백혈구의 내피세포 접착 억제를 그 기전으로 볼 수 있었으며, PGE-1을 술 중 투여함으로써 피판의 생존율을 향상시킬 수 있었다.

• Biomolecules & Therapeutics
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• 제20권6호
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• pp.520-525
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• 2012

Prostaglandin (PG) $E_2$, the most abundant prostaglandin in the human body, is synthesized from arachidonic acid via the actions of cyclooxygenase (COX) enzymes. $PGE_2$ exerts homeostatic, cytoprotective, inflammatory, and in some cases anti-inflammatory effects. Also, it has been reported that $PGE_2$ is involved in hair growth. Diphlorethohydroxycarmalol (DPHC) is a phlorotannin compound isolated from the brown algae Ishige okamurae, with various biological activities in vitro and in vivo. In this study, the biological effect and mechanism of action of DPHC on prostaglandin synthesis in HaCaT human keratinocytes was examined. The results showed that, in these cells, DPHC significantly and dose-dependently induced $PGE_2$ synthesis by increasing the protein and mRNA levels of COX-1 and COX-2. Interestingly, DPHC-induced COX-1 expression preceded that of COX-2. Also, while both rofecoxib and indomethacin inhibited $PGE_2$ production, the latter was seems to be the more potent. From above results, we can expect that DPHC has some beneficial effects via increasing of $PGE_2$ production.

• Restorative Dentistry and Endodontics
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• 제25권2호
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• pp.193-201
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• 2000

Prostaglandins (PGs) and Leukotrienes (LTs) have been implicated in the genesis of pulpal and periapical inflammation. In this study, the relationships among $PGE_2$, 6-keto-PG $F_1{\alpha}$ (a stable metabolite of $PGI_2$) and $LTB_4$ concentrations in inflamed pulp and periapical lesions were discussed. Pulp tissue were obtained in routine endodontic treatment and periapical lesions in periapical surgery after clinical diagnoses were made. These specimens were divided into four groups as normal pulp group (Control group), acute pulpitis group, chronic pulpitis group, and periapical lesion group. Pulp tissue and periapical lesions were stored in liquid nitrogen. The concentration of $PGE_2$, $PGI_2$ and $LTB_4$ were measured with ELISA. The data were analyzed by one-way ANOVA. Significantly higher levels of $PGE_2$, 6-keto-PG $F_1{\alpha}$ a and $LTB_4$ were found in acute pulpitis group than chronic pulpitis group and periapical lesion group(p<0.05). Periapical lesion group showed significantly higher mean concentrations of $PGE_2$ and $LTB_4$ than chronic pulpitis group. In control and chronic pulpitis group, significant higher levels of $PGI_2$ than $PGE_2$ and $LTB_4$ were found. These results suggested that the high levels of $PGE_2$ and $LTB_4$ in periapical lesions may be due to rich endothelium., fibroblast and lymphocyte known as the main producers of $PGE_2$ and $LTB_4$. $PGI_2$ may be thought to one of the most abundant PGs in normal pulp tissue.

• Archives of Reconstructive Microsurgery
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• 제9권2호
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• pp.179-185
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• 2000

In the field of microsurgery, the vascular obstruction of the microvascular anastomosis by thrombus is one of the most important complication. The purpose of this study is to compare the effect between aspirin and prostaglandin $E_1$($PGE_1$) which act as the peripheral vasodilatation and platelet disaggregation. We have used total 48 white male rats and divided them into three gruoups(A, B and C group). Each group consists of 16 rats respectively. A group is as control, B group is medicated with aspirin(3.0mg/kg/day) and C group with $PGE_1(1.2{\mu}g/kg/day)$. The gross and histopathologic findings at anastomosed site were observed on 3, 5, 10 and 15 days after vascular anastomosis and the results were obtained as the followings. 1. The microvascular patency rate is 81.2% in control group, 93.8% in aspirin group and 100% in $PGE_1$ group. 2. On the histologic examination, the formation of mural thrombus is decreased both in the aspirin and $PGE_1$ group as comparing with the control group and also the hypertrophy of the intima forming from media is less formed in $PGE_1$ group than aspirin group and the degree of thickeness is also less. 3. The fibrosis of media is less observed in $PGE_1$ group than aspirin group. According to the above results, the application of $PGE_1$ to the microsurgery is considered to be effective on the prevention of the thrombus formation and on providing high patency rate.

• Archives of Reconstructive Microsurgery
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• 제6권1호
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• pp.1-8
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• 1997

Recently prostaglandin $E_1(PGE_1)$ has been shown to ensure flap survival by producing vasodilation of the peripheral vessels and platelet disaggreation. However, direct observation and detailed quantitative studies of the effects of $PGE_1$ on the cutaneous microcirculation have not been reported. In the present study, we investigated cutaneous microcirculatory changes in the rabbit ear chamber(REC) with an intravital microscope following intravenous administration of $PGE_1$. The results obtained in this study indicate that $PGE_1$ administered intravenously at a rate of 200ng/kg/min might act directly on the vessels and cause dilatation of metarterioles and capillaries without affecting vasomotion and systemic blood pressure. Clinically in order to evaluate the effect of an intravenous administration of $PGE_1$ on the cutaneous microcirculation, cutaneous blood flow, skin temperature and transcutaneous $Po_2$ in the pedicle or free flap of operated patients were evaluated by the combination of several measurements following the administration of $PGE_1$. The present study suggests that improvement of cutaneous microcirculation by $PGE_1$ may enhance the survival rate of flap or replantation. Both vessel arterial ischemia and venous congestion are main factors of tissue necrosis in the flap surgery. Vasodilatory or antithrombotic agents have been used in salvage of flap necrosis. However, the therapeutic effects of those drugs are still not well elucidated. Recently prostaglandin $E_1(PGE_1)$ has been shown to ensure flap survival by producing vasodilatation of the peripheral vessels and platelet disaggregation[1-3]. Emerson and sykes[4] have obtained significant improvement in the flap survival in the rat using $PGI_2$. Suzuki et al.[5] have reported prolonged flap survival length by using $PGE_1$ in the rabbit and concluded that $PGE_1$ improved the microcircuration in the flap. However, direct observation and detailed quantitative studies of the effects of $PGE_1$ on the cutaneous microcirculation have not been reported. In the present study, we investigated microcirculatory changes in the rabbit ear chamber[6,7] with an intravital microscope following intravenous administration of $PGE_1$.

• Journal of Periodontal and Implant Science
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• 제34권2호
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• pp.345-356
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• 2004

The triclosan was shown to have anti-microbial and anti-inflammatory effect with inhibition of inflammatory mediators such as prostaglandin $E_2(PGE_2)$. The purpose of this study was to elucidate whether and how $PGE_2$ could be inhibited by triclosan in human gingival fibroblast. Human gingival fibroblast-1 cells (ATCC CRL2014) were pre-treated for 1 hour with triclosan (0.001 ${\mu}/ml{\sim}10$ ${\mu}/ml$) and then stimulated with $TNF-{\alpha}$ (1.0 ng/ml). $PGE_2$ synthesis was evaluated by ELISA and gene expression of COX-1 and COX-2 was evaluated by RT-PCR after $TNF-{\alpha}$, triclosan, and NS-398 (COX-2 inhibitor, 5, ${\mu}M$) and/ or cycloheximide (protein synthesis inhibitor, 2 ${\mu}g/ml$). Triclosan was cytotoxic to human gingival fibroblasts in the concentration higher than 1.0 ${\mu}g/ml$ for longer than 24 hours in tissue culture. The $PGE_2$ synthesis was inhibited by triclosan in dose-dependent manner. Greater COX-2 mRNA suppression was observed with triclosan (0.1 ${\mu}g/ml$) than with $TNF-{\alpha}$ alone, without change in COX-1 gene expression. Inhibitory effects of triclosan on $PGE_2$ synthesis disappeared in presence of cycloheximide. This study suggests that triclosan inhibit prostaglandin $E_2$ at the level of COX-2 gene regulation and require de novo protein synthesis.