• The Korean Journal of Mycology
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• v.31 no.2
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• pp.114-116
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• 2003

Platelet aggregation inhibitory and fibrinolytic activities of water and ethanol extracts from mushrooms were studied. The highest platelet aggregation inhibitory activity was 81.2% in the ethanol extract from fruiting body of Inonotus obliquus ASI 74006 and also were high in the ethanol extract from fruiting bodies of Fomitella fraxinea. The ethanol extract from the mycelia of Agaricus blazei Murill. ASI 1174 showed the strongest fibrinolytic activity as 9.6 unit. However fibrinolytic activities of other mushrooms were low or negligible.

• International Journal of Oral Biology
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• v.34 no.1
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• pp.43-48
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• 2009

Thrombin-induced platelet microbicidal protein (tPMP) is a small cationic peptide that exerts potent in vitro microbicidal activity against a broad spectrum of human pathogens, including Staphylococcus aureus and Streptococcus rattus BHT. Earlier evidence has suggested that tPMP targets and disrupts the bacterial membrane. However, it is not yet clear whether membrane disruption itself is sufficient to kill the bacteria or whether subsequent, presumably intracellular, events are also involved in this process. In this study, we investigated the microbicidal activity of rabbit tPMP toward S. rattus BHT cells in the presence or absence of a pretreatment with antibiotics that differ in their mechanisms of action. The streptocidal effects of tPMP on control cells (no antibiotic pretreatment) were rapid and concentration-dependent. Pretreatment of S. rattus BHT cells with either penicillin or amoxicillin (inhibitors of bacterial cell wall synthesis) significantly enhanced the anti-S. rattus BHT effects of tPMP compared with the effects against the respective control cells over most tPMP concentration ranges tested. On the other hand, pretreatment of S. rattus BHT cells with tetracycline or doxycycline (30S ribosomal subunit inhibitors) significantly decreased the streptocidal effects of tPMP over a wide peptide concentration range. Furthermore, pretreatment with rifampin (an inhibitor of DNA-dependent RNA polymerase) essentially blocked the killing of S. rattus BHT by tPMP at most concentrations compared with the respective control cells. These results suggest that tPMP exerts anti-S. rattus BHT activity through mechanisms involving both the cell membrane and intracellular targets.

• Korean Journal of Biological Psychiatry
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• v.1 no.1
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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.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.137.3-138
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• 2003

The major active components of EGb 761, extract of Ginkgo biloba leaves, include flavonoid glycosides and unique diterpenes known as ginkgolides. Ginkgolides are potent inhibitors of platelet activating factor. In this study, we investigated antiinflammatory activity of ginkgolides on the Complete Freund"s Adjuvant (CFA)-induced mice. The ginkgolides were extracted from commercially available EGb 761. This extracting procedure was done by sequential treatments of the EGb 761 with chloroform, methanol, and water. (omitted)tted)

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.2
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• pp.241-249
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• 1998

Platelet-activating factor(PAF) enhanced interleukin-1(IL-1) activity by the interaction with a specific receptor in rat alveolar macrophages. In this study, we investigated the role of endogenous arachidonate metabolites and intracellular calcium mobilization in the PAF-induced IL-1 activity. Alveolar macrophages were preincubated with 5-lipoxygenase and cyclooxygenase inhibitors 30 min before the addition of PAF and lipopolysaccharide(LPS). After 24h culture, IL-1 activity was measured in the supernate of sample using the thymocyte proliferation assay. Inhibition of 5-lipoxygenase by nordihydroguaiaretic acid and AA-861 completely blocked the PAF-induced enhancement of IL-1 activity with $IC_{50}\;of\;2\;{\mu}M\;and\;5\;{\mu}M$, respectively. In contrast, the inhibition of cyclooxygenase pathway by indomethacin and ibuprofen resulted in the potentiation in PAF-induced IL-1 activity with maximal effect at $1\;{\mu}M\;and\;5\;{\mu}M$, respectively. In addition, leukotriene $B_4$ and prostaglandin $E_2$ production were observed in PAF-stimulated alveolar macrophage culture. As could be expected, 5-lipoxygenase and cyclooxygenase inhibitors abolished PAF- stimulated leukotriene $B_4$ and prostaglandin $E_2$ production, respectively. The effects of PAF on intracellular calcium mobilization in alveolar macrophages were evaluated using the calcium-sensitive dye fura-2 at the single cell level. PAF at any dose between $10^{-16}\;and\;10^{-8}$ M did not increase intracellular calcium. Furthermore, there was no effective change of intracellular calcium level when PAF was added to alveolar macrophages in the presence of LPS or LPS+LTB4, and 4, 24 and 48h after treatment of these stimulants. Together, the results indicate that IL-1 activity induced by PAF is differently regulated through subsequent induction of endogenous 5-lipoxygenase and cyclooxygenase pathways, but not dependent on calcium signalling pathway.

• BMB Reports
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• v.44 no.2
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• pp.140-145
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• 2011

Impaired responsiveness of platelets to epinephrine (epi) and other catecholamines (CA) has been reported in approximately 20% of the healthy Korean and Japanese populations. In the present study, platelet aggregation induced by epi was potentiated by RO 31-8220 (RO) or G$\ddot{o}$ 6983 (G$\ddot{o}$). Phosphorylated Akt (p-Akt) was very low in epi-stimulated PRP from CA-hypo- responders (CA-HY), whereas it was detected in those from CA-good responders (CA-GR). RO and G$\ddot{o}$ increased p-Akt, one of the major downstream effectors of phosphoinositol-3 kinase (PI3K), in epi-stimulated PRP from both groups. Wortmannin, a PI3K inhibitor, attenuated the RO or G$\ddot{o}$-induced potentiation of p-Akt in epi-stimulated PRP, suggesting positive effects for RO and G$\ddot{o}$ on PI3K. $TXA_2$ formation was increased by the addition of either RO or G$\ddot{o}$ in epi-stimulated platelets. The present data also suggest that impaired Akt phosphorylation may be responsible for epinephrine hypo-responsiveness of platelets.

• Natural Product Sciences
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• v.26 no.4
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• pp.259-267
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• 2020

Snakebite is a severe medical, economic, and social problem across the world, mostly in the tropical and subtropical area. These regions of the globe have typical of the world's venomous snakes present where access to prompt treatment is limited or not available. Snake venom is a complex mixture of toxin proteins like neurotoxin and cardiotoxin, and other enzymes like phospholipase A2 (PLA2), haemorrhaging, transaminase, hyaluronidase, phosphodiesterase, acetylcholinesterase, cytolytic and necrotic toxins. Snake venom shows a wide range of biological effects like anticoagulation or platelet aggregation, hemolysis, hypotension and edema. Phospholipase A2 is the principal constituent of snake venom; it catalyzes the hydrolysis of the sn-2 position of membrane glycerophospholipids to liberate arachidonic acid, which is the precursor of eicosanoids including prostaglandins and leukotrienes. The information regarding the structure and function of the phospholipase A2 enzyme may help in treating the snakebite victims. This review article constitutes a brief description of the structure, types, mechanism occurrence, and tests of phospholipase A2 and role of components of medicinal plants used to inhibit phospholipase A2.

• Journal of Korean Neurosurgical Society
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• v.61 no.2
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• pp.201-211
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• 2018

Objective : The purpose of this study was to analyze the variability of clopidogrel responses according to duration of a clopidogrel drug regimen after stent-assisted coil embolization (SAC), and to determine the correlation between the variability of clopidogrel responses and thromboembolic or hemorrhagic complications. Methods : A total of 47 patients who underwent SAC procedures to treat unruptured intracranial aneurysms were enrolled in the study. Preoperatively, patients received more than seven days of aspirin (100 mg) and clopidogrel (75 mg), daily. P2Y12 reaction unit (PRU) was checked with the VerifyNow test one day before the procedure (pre-PRU) and one month after the procedure (post-PRU). PRU variability was calculated as the difference between the initial response and the follow-up response. Patients were sorted into two groups based on their response to treatment : responsive and hypo-responsive. Results : PRU variability was significantly greater in the hypo-responsive group when compared to the responsive group (p=0.019). Pre-PRU and serum platelets counts were significantly correlated with PRU variation (p=0.005 and p=0.004, respectively). Although thromboembolic complication had no significant correlated factors, hemorrhagic complication was correlated with pre-PRU (p=0.033). Conclusion : In conclusion, variability of clopidogrel responses during clopidogrel medication was correlated to serum platelet counts and the initial clopidogrel response. Thromboembolic and hemorrhagic complications did not show correlation with the variability of clopidogrel response, or the clopidogrel response after one month of medication; however, hemorrhagic complication was associated with initial clopidogrel response. Therefore, it is recommended to test patients for an initial clopidogrel response only, as further tests would be insignificant.

• Animal Bioscience
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• v.36 no.8
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• pp.1180-1189
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• 2023

Objective: Discovering the mechanism of cell specification is important to manipulate cellular lineages. To obtain lineage-specific cell lines, the target lineage needs to be promoted, and counterpart lineages should be suppressed. Embryos in the early blastocyst stage possess two different cell populations, the inner cell mass (ICM) and trophectoderm. Then, cells in the ICM segregate into epiblasts (Epi) and primitive endoderm (PrE). PrE cells in embryos show specific expression of platelet-derived growth factor (PDGF) and its receptor, PDGF receptor A (PDGFRA). In this study, we suppressed PDGF signaling using two methods (CRISPR/Cas9 injection and inhibitor treatment) to provide insight into the segregation of embryonic lineages. Methods: CRISPR/Cas9 RNAs were injected into parthenogenetically activated and in vitro fertilized embryos. The PDGF receptor inhibitor AG1296 was treated at 0, 5, 10, and 20 µM concentration. The developmental competence of the embryos and the number of cells expressing marker proteins (SOX2 for ICM and SOX17 for PrE) were measured after the treatments. The expression levels of the marker genes with the inhibitor were examined during embryo development. Results: Microinjection targeting the PDGF receptor (PDGFR) A reduced the number of SOX17-positive cell populations in a subset of day 7 blastocysts (n = 9/12). However, microinjection accompanied diminution of Epi cells in the blastocyst. The PDGF receptor inhibitor AG1296 (5 µM) suppressed SOX17-positive cells without reducing SOX2-positive cells in both parthenogenetic activated and in vitro fertilized embryos. Within the transcriptional target of PDGF signaling, the inhibitor significantly upregulated the Txnip gene in embryos. Conclusion: We identified that PDGF signaling is important to sustain the PrE population in porcine blastocysts. Additionally, treatment with inhibitors was a better method to suppress PrE cells than CRISPR/Cas9 microinjection of anti-PDGF receptor α gene, because microinjection suppressed number of Epi cells. The PDGF receptor might control the number of PrE cells by repressing the proapoptotic gene Txnip. Our results can help to isolate Epi-specific cell lines from blastocysts.

• Korean Journal of Head & Neck Oncology
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• v.16 no.1
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• pp.20-25
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• 2000

The medicinal leech, Hirudo medicinalis, has been used for salvage of the venous-congested flap following reconstructive surgery, with increasing frequency during the last two decades. Medicinal leech therapy is a safe, efficacious, economical, and well-tolerated intervention. The flap salvage with leeching occurs in approximately 70% of cases, and leeches need to be used as early as possible. At the time of the bite, evacuation of blood and injection of the leech saliva products, including anticoagulants and inhibitors of platelet aggregation, maintain capillary circulation of the flap, and then venous capillary return is established across the wound by angiogenesis. One of the salivary products, hirudin, represents the first parenteral anticoagulant introduced since the discovery of heparin. We analyzed two cases in which flap salvage with leeching was attempted, and reviewed medicinal leech therapy on the basis of our experiences and literature review. This has not been documented in the head and neck surgery literature in our country.