• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.137.2-138
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• 2003

The steam distillate obtained from sawdust of Thujopsis dolabrata var. hondai was fractionated by centrifugal thin-film evaporation. and then the fractions were investigated against antiplatelet activity using washed rabbit platelets in vitro. The biologically active constituent of T. dolabrata sawdust was isolated by silica gel column chromatography and HPLC and characterized as carvacrol by various spectral analysis ($^{1}H$, $^{13}C$-NMR and GC/MS studies). (omitted)

• 생물정신의학
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• 제1권1호
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• pp.88-97
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• 1994

Many evidences are compatible with the correlation between the inhibition of [$^3H$] imipramine([$^3H$]IMI) and [$^3H$]paroxetine([$^3H$]PAT) binding to the 5-hydroxytryptamine(5-HT) transporter complex and the 5-HT uptake of 5-HT neurons and platelets, and most antidepressants have been shown to inhibit the [$^3H$]IMI and [$^3H$]PAT binding and the neuronal 5-HT uptake. However, several paradoxical research findings led to doubt about the pharmacological significance of the [$^3H$]IMI and [$^3H$]PAT binding sites. This study was carried to clarify the correlation between the [$^3H$]IMI and [$^3H$]PAT binding parameters and the tissue 5-HT content or/and [$^3H$]5-HT uptake in the rabbit platelet, which contains 40 times ad much 5-HT as that of human platelet and shows the 10 fold higher $B_{max}$ of the 5-HT transporter binding to a 5-HT uptake inhibitor. The rabbits were treated for 28 days with amitriptyline(4mg/kg/day : AP), fluoxetine(0.5mg/kg/day : FO), and sertraline(0.5mg/kg/day : SA) via an Alzet osmotic pump implanted for constant infusion. The [$^3H$]IMI binding $B_{max}$ and $K_d$ of the rabbit platelets were $6.4{\pm}1.2$pmol/mg protein and $10.9{\pm}2.1$nM and those in the [$^3H$]PAT binding were $8.6{\pm}1.1$pmol/mg protein and $1.6{\pm}0.3$nM, respectively. AP slightly increased $B_{max}$ of [$^3H$]IMI binding and both [$^3H$]IMI binding and [$^3H$]PAT binding $K_d$, and i contrast, it slightly decreased $B_{max}$ of [$^3H$]PAT binding. FO Slightly increased $K_d$ of both and [$^3H$]IMI and [$^3H$]PAT binding and slightly decreased $B_{max}$ of [$^3H$]IMI and [$^3H$]PAT binding. SA produced the significant increase of [$^3H$]PAT binding $B_{max}$ and the slight increase of both [$^3H$]IMI and [$^3H$]PAT binding $K_d$ and in contrast, it slightly decreased $B_{max}$ and of [$^3H$]IMI binding. And, the $V_{max}$ and $K_m$ of platelet [$^3H$]5-HT uptake were $24.2{\pm}2.4$pmol/$10^8$ platelets/min and $3.3{\pm}0.3$nM, respectively. The $V_{max}$ was little affected by AP, FO, or SA, but the [$^3H$]5-HT uptake $K_m$ value was moderately increased by FO. However, the platelet 5-HT content was moderately decreased by all of the 5-HT uptake inhibitors used in this study. These results seem to be consistent with the allosterical and competitive interaction of 5-HT uptake inhibiting antidepressants with each other as well as 5-HT in the 5-HT transporter binding, and provide no support for the view that the potencies of 5-HT uptake inhibitors to inhibit the [$^3H$]IMI or [$^3H$]PAT binding with 5-HT transporter complex correlate with their antidepressant potencies.

• 대한수의학회지
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• 제36권4호
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• pp.873-886
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• 1996

For better understanding the interrelationship of hemorrhage and aggregation mechanism, cyclopiazonic acid(CPA) known as promoting the aggregation of platelet, aflatoxin $B_1(AFB_1)$ inhibiting platelet aggregation were used as toxic mycotoxins in these studies. In order to investigate the potential role of prostaglandin metabolism on the platelet aggregation, a variety of prostaglandin metabolites such as $PGF_{2{\alpha}}$, $PGE_2$ and $TXB_2$ were measured in homogenized rabbit platelets by TLC and LSC. And the role of $Ca^{{+}{+}}$ on the platelet aggregation was investigated by flow cytometer. Finally, the morphological effects of mycotoxins on platelet were determined by transmission electron microscope. The results and conclusions obtained from these studies are: 1) CPA induced no changes but $AFB_1$ increased $PGE_2$ and $TXB_2$. 2) CPA promoted ADP, collagen, thrombin, A.A., and PAF-induced $Ca^{{+}{+}}$ release. $AFB_1$, however, decreased $Ca^{{+}{+}}$ level except collagen-induced $Ca^{{+}{+}}$ release. When the calcium blocker, verapamil, was used, CPA decreased thrombin-induced $Ca^{{+}{+}}$ release and increased collagen, ADP, PAF and A.A.-induced $Ca^{{+}{+}}$ release. $AFB_1$ in contrast decreased the all factors induced $Ca^{{+}{+}}$ release. 3) $AFB_1$ did not induce any ultrastructural changes except large vacuole formation in a few platelets. And CPA also did not induce any changes except moderate shape change, indicator of platelet activation. In conclusion, CPA promoted platelet aggregation by the increases of $Ca^{{+}{+}}$ release but had no changes in A.A. metabolites. Antiaggregating effects of $AFB_1$ may be due to decreases of $Ca^{{+}{+}}$ release and increases of $PGE_2$ and $PGF_{2{\alpha}}$ formation. These data provide the basis for the future study of mobilization and function of $Ca^{{+}{+}}$ in platelet aggregation.

• 대한약리학회지
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• 제31권3호
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• pp.299-311
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• 1995

혈소판은 혈전기전의 중요요소로, monoamine성 신경전달물질의 대사에 있어서 신경계와 유사점을 가지고 있다. 따라서 항우울약물인 amitriptyline (AMT)과 sertraline (SRT)의 혈소판응집 억제와 이에 의한 세포내 신호전달 물질의 함량변동 및 단백인산화에 대한 영향을 chlorpromazine (CPZ)과 비교연구함으로써, 이들 약물의 혈소판응집 억제작용의 효능을 검정하고, 항 혈소판 및 항우울 작용기전의 일단을 규명하고자 하였다. SRT, CPZ 및 AMT은 thrombin (0.25 unit/ml)에 의한 혈소판응집을 억제하였으며, 각각의 IC50은 $4.37{\times}10^{-5}\;M$, $5.76{\times}10^{-5}\;M$ 및 $1.15{\times}10^{-4}\;M$이었다. 이러한 억제효과는 A23187$(1.0\;{\mu}M)$및 PMA(320 nM)에 의한 혈소판응집에 대해서도 유사하게 나타났다. thrombin은 혈소판응집과 아울러 thromboxane $B_2$ 및 $prostaglandin\;E_2$ 생성을 유의하게 증가시켰으며, 이러한 arachidonic acid 생성은 CPZ, AMT 및 SRT에 의하여 현저하게 억제되었다. CPZ, AMT 및 SRT은 cAMP 함량을 용량의존적으로 감소시켰으며, SRT, AMT $(1{\times}10^{-4}\;M)$ 및 CPZ $(3{\times}10^{-5}\;M)$은 cGMP 함량을 증가시키는 경향을 보였다. 한편, $Ins(1,4,5)P_3$ 함량은 thrombin 부하 후 10초 이내에 정점에 도달한 후 45초 이후까지 유지된다. CPZ과 AMT은 혈소판의 $Ins(1,4,5)P_3$ 함량을 현저히 증가시키며, thrombin에 의한 증가도 유의하게 증강시킨다. SRT은 혈소판의 $Ins(1,4,5)P_3$을 증가시키나, thrombin 부하 후 증강되지는 않았다. $Ins(1,4,5)P_3$ 증가에 이어서, $[Ca^{2+}]_i$은 thrombin 부하 후 20초에 최고점에 이르며, 이러한$[Ca^{2+}]_i$, 증가는 세 약물에 의하여 현저하게 억제되었다. 혈소판 단백인산화에 대해서, thrombin은 $41{\sim}43\;kDa$ 및 20kDa 단백인산화를 현저하게 증가시켰으며, 이는 AMT, SRT 및 CPZ에 의하여 억제되었다. CPZ, AMT 및 SRT 등의 세 약물은 유의한 항응집효과와 thromboxane생성억제 효과를 나타냈으며, 이들 약물에 의한 protein kinase C 활성억제 및 $Ins(1,4,5)P_3$의 함량증가는 각각 이들약물의 항응집효과 및 항우울성 작용기전과 연관될 수 있음을 시사한다.

• 한국식품위생안전성학회지
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• 제19권3호
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• pp.161-166
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• 2004

We investigated the antiplatelet effect of a newly synthesized guanidine derivative KR-32558, a sodium-hydrogen exchanger-1 (NHE-1) inhibitor, together with the elucidation of the possible mechanisms of action. KR-32558 concentration -dependently inhibited the aggregation of washed rabbit platelets induced by collagen (10 ${\mu}g/ml$) with an $IC_{50}$ value of 85.9 ${\mu}M$, but with much weaker potency against aggregation induced by thapsigargin (0.5 ${\mu}M$) or A23187 (5 ${\mu}M$). And had no effect on platelet aggregation induced by arachidonic acid (100 ${\mu}M$), thrombin (0.05 U/ml) and U46619 (1 ${\mu}M$) up to 100 ${\mu}M$. KR-32558 completely inhibited the $[Ca^{2+}]_i$ mobilization induced by collagen at concentration of 100${\mu}iM$. Taken together, these observation suggest that KR-32558 selectively inhibited collagen-mediated platelet aggregation by blocking the cytoplasmic calcium mobilization in addition to NHE-1 inhibition.

• Journal of Microbiology and Biotechnology
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• 제15권2호
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• pp.425-427
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• 2005

The steam distillate obtained from Thujopsis dolabrata var. hondai sawdust was fractionated by centrifugal thin-film evaporation, and the fractions were then investigated for antiplatelet activity using washed rabbit platelets. The biologically active constituent of T. dolabrata var. hondai sawdust was isolated by silica gel column and HPLC chromatographies and characterized as carvacrol by various spectral analyses. Carvacrol inhibited platelet aggregation induced by collagen, arachidonic acid, and platelet activating factor with IC$_{50}$ values of 12.6, 2.5, and 385.3 $\mu$M, respectively. However, carvacrol had no effect on thrombin, calcium ionophore A23l87, or phorbol l2-myristate l3-acetate induced platelet aggregation. Carvacrol was a much more potent inhibitor, as antiplatelet agents, compared with aspirin. These results suggest that carvacrol isolated from T. dolabrata var. hondai sawdust may be useful as a lead compound for inhibiting arachidonic acid-induced platelet aggregation.

• 대한치과보철학회지
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• 제39권6호
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• pp.659-681
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• 2001

Platelet-rich plasma(PRP) has been known to increase the rate and degree of bone formation by virtue of growth factors in concentrated platelets. Although its great healing effect on bone defect or pre-implantation site preparation in conjunction with bone substitute has been reported, the effect associated with implant is unknown. The purpose of this study was to investigate the effect of PRP on rapid osseointegration of endosseous dental implants in the rabbit tibiae. Twenty two adult female New Zealand white rabbits, weighing approximately 2.7-3.3kg, were used for this study. Twelve of the 22 animals were used for histomorphometric analysis and ten of the 22 were for removal torque test. Each animal received two implants in each tibia (two treated with PRP and two as control) and was given fluorochrome intramuscularly. For histomorphometric analysis, rabbits were divided into four groups according to the healing period. At 1 week, 2 weeks, 4 weeks and 8 weeks postoperatively, each three animals were sacrificed serially and the amount and rate of bone formation around dental implant were examined on the undecalcified sections under fluorescent microscope, polarized microscope and light microscope connected to a personal computer equipped with image analysis system. For removal torque test, rabbits were divided into two groups and removal torque tests were performed at 4 weeks, 10 weeks after implant placement. In total, 88 screw shaped, commercially pure titanium implants (Neoplant, Neobiotech, Seoul, Korea) were used in this study. Labeling pattern reflected differences of two groups in bone formation rate at each period. Histomorphometrically, PRP group showed significantly higher bone volume within threads compared to control group at 2 weeks ($70.30{\pm}4.96%$ vs. $50.68{\pm}6.33%$; P < .01) and 4 weeks ($82.59{\pm}5.94%$ vs. $72.94{\pm}4.57%$; P < .05 ). PRP group at 1, 2 and 4 weeks revealed similar degree of bone volume formation comparable to control group at 2, 4 and 8 weeks, respectively. On the other hand, while PRP group showed higher bone-implant contact ($47.37{\pm}8.09%$) than control group ($33.16{\pm}13.47%$) at 2 weeks, there were no significant differences between PRP group and control group for any experimental period. Removal torque values also showed no significant differences between PRP group and control group at any experimental period (P > .05). These findings imply that PRP could induce rapid, more bone formation around implant during early healing period and get faster secondary stability for reducing healing period, though it has not induced bone maturation enough to resist functional loading.

• Archives of Plastic Surgery
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• 제34권3호
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• pp.291-297
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• 2007

Purpose: Platelet-rich plasma(PRP) contains protein growth factors, which are actively secreted by platelets to promote wound healing. However, it is not clear whether the injection of PRP into the autologous fat grafts increases the survival rate and the degree of angiogenesis. Methods: New Zealand White rabbit ears were injected fat with PRP, saline, insulin or isoproterenol (n=8/each group) for observation of the survival and degree of angiogenesis of the injected fat. The volume of the harvested fat and the degree of angiogenesis from dorsum of rabbit ears were evaluated 4, 8, and 12 weeks after the autologous fat graft. The degree of angiogenesis was measured with microvascular density (MVD) counts. Results: The volume of harvested fat decreased in a time-dependent manner after autologous fat grafts, but the decrease rate in volume of harvested fat was slower in PRP-injected group compared to that of other control groups. The difference in the volume of the harvested fat between PRP-injected group and other control groups became significant from 4 weeks after the autologous fat graft, and was maintained up to 12 weeks. However, there was no significant difference between PRP-injected group and insulin-injected group 8 and 12 weeks after the autologous fat graft. On the contrary, MVD counts increased in a time-dependent manner after autologous fat grafts. The MVD counts were significantly higher in PRP-and insulin-injected groups than in other control groups from 4 weeks after the autologous fat graft, and these differences were maintained up to 12 weeks. There was no correlation between mean platelet numbers and the volume of harvested fat. Conclusion: The present study demonstrates that PRP-injection into autologous fat grafts increases the survival rate and the degree of angiogenesis. Thus, PRP injection with autologous fat grafts would be a promising tool for maintaining the volume of the grafted fat.

• Biomolecules & Therapeutics
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• 제14권3호
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• pp.160-165
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• 2006

Since platelet-activating factor (PAF) is involved in inflammation, allergic response and anaphylactic shock, PAF receptor antagonists may have potential for controlling these disease conditions. The extract of the leaves of Ginkgo biloba having a higher content of terpenoids (12%) with flavonoids (24%) (YY1224) was prepared in order to obtain the increasing PAF antagonistic activity. As expected, YY1224 showed a higher PAF antagonistic binding affinity ($IC_{50}\;=\;0.09\;{\mu}g/ml$) using $[^3H]PAF$ and rabbit platelets as ligand and receptor source, compared with an $IC_{50}$ of $>\;100\;{\mu}g/ml$ by Egb 761, a standardized extract. YY1224 also showed a higher inhibitory activity against PAF-induced platelet aggregation and NO production from lipopolysaccharide-treated RAW 264.7 cells. In addition, it protected PAF-induced death in mice by oral administration at 15 mg/kg. All these results suggest that YY1224 may show favorable effects on PAF-related disorders.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제27권2호
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• pp.140-150
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• 2005

Maxillary sinus lifting procedure and bone grafting are used to reconstruct atrophic maxillae. These procedure are usually followed by the placement of endosseous dental implants. Different materials and techniques can be used for sinus bone grafting. Platelets are known to contain various growth factors involved in the repair of the vasculature and tissues, and it is known that the specialized platelet secretory granules, the alpha granules, contain platelet derived growth factor(PDGF), transforming growth factor-beta(TGF-beta), insuline like growth factor-I(IGF-I), epidermoid growth factor(EGF), and others. This study was to evaluate the effect of PRP on bone formation in a sinus bone grafting. Twelve rabbits were included in this randomized, blinded, prospective pilot study. In experimental group, sinus bone grafting with autobone and platelet rich plasma. In control group, sinus bone grafting with only autobone. Rabbits were sacrificed at 2nd, 4th, 8th, 12th weeks postoperatively. Clinical and radiographic tests, histological analysis were conducted to compare both sides. In clinical examination, there in no significant difference between experimental group and control group. But, in radiographic examination, a distinct incresed in the radiopaque of the PRP experimental group at 2nd and 4th weeks. The histologic examination revealed that more new bone formation and osteoblast activity were seen in experimental group at 2nd and 4th weeks. In conclusion, PRPs action in sinus bone grafting had a capacity of increased new bone formation in a early bone healing stage.