• Natural Product Sciences
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• v.6 no.1
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• pp.25-30
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• 2000

To analyse scientifically the fundamental formulation theory and drug interaction of Chungpegagan-tang, the extraction level of puerarin and daidzin, the transforming activity of puerarin and daidzin to daidzein by human intestinal bacteria and in vitro cytotoxicity against tumor cell lines of Chungpesagan-tang were investigated. When Puerariae Radix was extracted with Chungpesagan-tang composing herbal medicines, the puerarin extraction level from these polyprescriptions was decreased by the extraction with Raphani Semen or Cimicifugae Rhizoma, but the other herbal medicines increased it. The activity transforming puerarin and daidzin to daidzein by human intestinal bacteria was increased by Raphani Semen, Cimicifugae Rhizoma and Angelicae Tenuissimae Radix, but decreased by Scutellariae Radix and Rhei Rhizoma. Puerariae Radix did not showed in vitro cytotoxicity against tumor cell lines. However, by its anaerobic incubation with human intestinal bacteria, it showed a potent cytotoxicity. When the main components, puerarin and daidzin, of Puerariae Radix were incubated with human intestinal bacteria, the main metabolites were daidzein and calycosin. These metabolites had the most potent cytotoxicity, compared to those of puerarin and daidzin. Raphani Semen, Rhei Rhizoma and Chungpesagan-tang had also the potent cytotoxicity against tumor cell lines by the anaerobic incubation with human intestinal bacteria.

• Journal of Pharmaceutical Investigation
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• v.27 no.1
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• pp.39-49
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• 1997

Nicotinic acid was mixed with glass powders such as controlled pore glass (CPG), glyceryl controlled pore glass (GPG) and glass beads (GB) at room temperature. The physicochemical properties of nicotinic acid in the various mixtures were examined by differential thermal analysis, X-ray diffraction study. Infrared spectroscopy and BET gas adsorption measurements. The peak area at the melting point from the various mixtures of nicotinic acid and CPG was increased with an increase of nicotinic acid concentration while the broad peak area was remained unchanged in the DTA curve. As shown in the powder X-ray diffraction patterns, the crystalline peaks of nicotinic acid disappeared in mixture with CPG, suggesting the interaction of nicotinic acid and porous powders. It was found that the larger the content of CPG, the higher the ratio of an amorphous state to a crystalline state. BET isotherm showed that as the amount of nicotinic acid was increased, the specific surface area was reduced proportionally to nicotinic acid content of up to 40% and remained constant thereafter. Sublimation of nicotinic acid from the mixture of nicotinic acid and CPG was examined. A large quantity of nicotinic acid was retained in the mixture when stored on various temperatures in vacuo for 10 hours. The nicotinic acid mixtures with CPG or GPG showed a high dissolution rates of nicotinic acid in aqueous solution, especially in the initial dissolution stage. CPG is expected to be a good pharmaceutical excipient to reduce the crystallinity of drugs and to prevent sublimation of drugs.

• The Korean Journal of Pain
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• v.26 no.4
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• pp.374-378
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• 2013

Background: Incisional pain is particularly troublesome after hysterectomy. A method called transversus abdominis plane block (TAPB) has shown promise in managing postoperative pain. In this study, we evaluated the analgesic efficacy of ultrasound-guided TAPB after hysterectomy at different time points and at each time point separately for 48 hours. Methods: Forty-two patients (ASA I, II) who were electively chosen to undergo total abdominal hysterectomy were divided into 2 groups, control (group C) and intervention (group I). Twenty-one patients underwent TAPB (group I) and 21 patients received only the standard treatment with a fentanyl pump (group C). Both groups received standard general anesthesia. For patients in group I, following the surgery and before emergence from anesthesia, 0.5 mg/kg of ropivacaine 0.2% (about 20 cc) was injected bilaterally between the internal oblique and transverse abdominis muscles using sonography. Pain scores using the Visual Analogue Scale (VAS) and drug consumption were measured at 2, 6, 12, 24, and 48 hours after TAPB. Results: There were no significant differences in demographics between the two groups. VAS scores appeared to be lower in group I, although there was no interaction with time when we compared mean VAS measurements at different time points between group I and group C (P > 0.05). The amount of fentanyl flow was consistently higher in group C, but when we compared the two groups at each time point separately, the observed difference was not statistically significant (P < 0.053). The incidence of vomiting was 10% in group I and 28% in group C. There were no complaints of itching, and sedation score was 0 to 3. There were no complications. Conclusions: This study showed that TAPB did not result in a statistically significant decrease in VAS scores at different time points. TAPB did lead to decreased fentanyl flow, but when we compared the two groups at each time point separately, the observed difference was not statistically significant.

• Reproductive and Developmental Biology
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• v.39 no.4
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• pp.105-115
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• 2015

Toll-like receptor 7 (TLR7) is critical for the triggering of innate immune response by recognizing the conserved molecular patterns of single-stranded RNA (ssRNA) viruses and mediated antigenic adaptive immunity. To understand how TLR7 distinguish pathogen-derived molecular patterns from the host self, it is essential to be able to identify TLR7 receptor interaction interfaces, such as active sites or R848-agonist binding sites. The functional interfaces of TLR7 can serve as targets for structure-based drug design in studying the TLR7 receptor's structure-function relationship. In contrast to mammalian TLR7, chicken TLR7 (chTLR7) is unknown for its important biological function. Therefore, it has been targeted to mediate contrasting evolutionary patterns of positive selection into non-synonymous SNPs across eleven species using TLR7 conservation patterns (evolutionary conserved and class-specific trace residues), where protein sequence differences to the TLR7 receptors of interest record mutation that have passed positive section across the species. In this study, we characterized the Lys609 residue on chTLR7-ECD homodimer interfaces to reflect the current tendency of evolving positive selection to be transfer into a stabilization direction of the R848-agonist/chTLR7-ECDs complex under the phylogenetically variable position across species and we suggest a potential indicator for contrasting evolutionary patterns of both the species TLR-ECDs.

• The Korean Journal of Physiology and Pharmacology
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• v.14 no.6
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• pp.353-358
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• 2010

This study demonstrates the ability of magnolol, a hydroxylated biphenyl compound isolated from Magnolia officinalis, to inhibit LPS-induced expression of iNOS gene and activation of NF-${\kappa}B$/Rel in RAW 264.7 cells. Immunohisto-chemical staining of iNOS and Western blot analysis showed magnolol to inhibit iNOS gene expression. Reporter gene assay and electrophoretic mobility shift assay showed that magnolol inhibited NF-${\kappa}B$/Rel transcriptional activation and DNA binding, respectively. Since p38 is important in the regulation of iNOS gene expression, we investigated the possibility that magnolol to target p38 for its anti-inflammatory effects. A molecular modeling study proposed a binding position for magnolol that targets the ATP binding site of p38 kinase (3GC7). Direct interaction of magnolol and p38 was further confirmed by pull down assay using magnolol conjugated to Sepharose 4B beads. The specific p38 inhibitor SB203580 abrogated the LPS-induced NF-${\kappa}B$/Rel activation, whereas the selective MEK-1 inhibitor PD98059 did not affect the NF-${\kappa}B$/Rel. Collectively, the results of the series of experiments indicate that magnolol inhibits iNOS gene expression by blocking NF-${\kappa}B$/Rel and p38 kinase signaling.

• The Korean Journal of Pharmacology
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• v.18 no.2
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• pp.69-77
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• 1982

$Na^+,\;K^+-ATPase$ is a component of plasma membrane in almost all animal cell, and maintains ionic distribution and membrane potential of normal cell. In the mechanism of adrenergic transmission, it is relatively well known that drug-receptor combination leads to stimulate adenylate cyclase and so on. In the cholinergic transmisison, the mechanism is not well known but is simply interpreted as the change of membrane permeability results from acetylcholine receptor interaction. To study the relationship between cholinergic transmission and membrane $Na^+,\;K^+-ATPase$, the effect of carbachol on $Na^+,\;K^+-ATPase$ activity in rabbit erythrocyte membrane is studied. The results are summarized as follows. 1) Total ATPase, $Mg^{+2}-ATPase$ and $Na^+,\;K^+-ATPase$ of rabbit erythrocyte membrane show maximum activities at 1mM of tris-ATP. 2) Total ATPase activity tends to increase when treated with carbachol $(10-^{-9}M-10^{-3}M)$. 3) The $Mg^{+2}-ATPase$ activity also tends to increase when treated with carbachol $(10-^{-9}M-10^{-3}M)$. 4) The $Na^+,\;K^+-ATPase$ activity is inhibited when treated with carbachol $(10-^{-9}M-10^{-7}M)$. It is suggested that the inhibition of $Na^+,\;K^+-ATPase$ by cholinergic drugs may be considered as one part of mechanism of cholinergic transmission.

• The Korean Journal of Physiology
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• v.24 no.1
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• pp.115-121
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• 1990

The interaction between a calcium channel blocker nifedipine and atrial natriuretic peptide (ANP) was examined in normotensive and renal hypertensive rats. The infusion of either ANP or nifedipine produced a significant decrease in mean arterial pressure (MAP). The combined infusion of ANP with nifedipine resulted in a greater fall of MAP than did the infusion of each drug alone. ANP significantly increased urinary volume and excretion of sodium, while nifedipine was without effects. The diuretic/natriuretic effects of ANP were potentiated by the combined infusion with nifedipine. The vasodepressor and renal effects of ANP or nifedipine were qualitatively similar between the normotensive and hypertensive rats. Nifedipine caused an upward and leftward shift of the ANP dose-relaxation curve of the phenylephrine-precontracted thoracic aortic rings isolated from the normotensive rats , suggesting that the vasodilation sensitivity to ANP is increased in the presence of nifedipine. These results indicate that nifedipine enhances the vasodepressor effect of ANP, the likely mechanisms being attributable to a contraction of effective intravascular volume as a consequence of potentiated renal excretion and a greater peripheral vasodilation.

• Polymer(Korea)
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• v.34 no.1
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• pp.79-83
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• 2010

Alginate beads were prepared using poly(N-isopropylacrylamide-co-dimethylamino ethyl methacrylate)(P(NIPAM-co-DMAEMA)). First, P(NIPAM-co-DMAEMA) was immobilized on the surface of alginate beads by taking advantage of electrostatic interaction between alginate and P(NIPAM-co-DMAEMA). Second, P(NIPAM-co-DMAEMA) was contained in the matrix of alginate beads. P(NIPAM-co-DMAEMA) were prepared by a free radical polymerization at $74^{\circ}C$ for 12 h. The weight ratio of NIPAM to DMAEMA monomer was 95/5. The copolymer was identified by $^1H$-NMR. Releases from the alginate beads were observed at 30, 37, and $45^{\circ}C$ using blue dextran or FITC-dextran(fluorescein isothiocyanate-dextran) as a model drug. The effect of temperature on the degree of release from the beads was insignificant. FITC-dextran was released more than blue dextran possibly due to its smaller molecular weight.

• Journal of Veterinary Clinics
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• v.21 no.3
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• pp.253-258
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• 2004

DNA double-strand break (DSB) is a serious treat for the cells including mutations, chromosome rearrangements, and even cell death if not repaired or misrepaired. Ku heterodimer regulatory DNA binding subunits (Ku70/Ku80) bound to double strand DNA breaks are able to interact with 470-kDa DNA-dependent protein kinase catalytic subunit (DNA-PKcs), and the interaction is essential for DNA-dependent protein kinase (DNA-PK) activity. The Ku80 mutants were designed to bind Ku70 but not DNA end binding activity and the peptides were treated in breast cancer cells for co-therapy strategy to see whether the targeted inhibition of DNA-dependent protein kinase (DNA-PK) activity sensitized breast cancer cells to ionizing irradiation or chemotherapy drug to develop a treatment of breast tumors by targeting proteins involved in damage-signaling pathway and/or DNA repair. We designed domains of Ku80 mutants, 26 residues of amino acids (HN-26) as a control peptide or 38 (HNI-38) residues of amino acids which contain domains of the membrane-translocation hydrophobic signal sequence and the nuclear localization sequence, but HNI-38 has additional twelve residues of peptide inhibitor region. We observed that the synthesized peptide (HNI-38) prevented DNA-PKcs from binding to Ku70/Ku80, resulting in inactivation of DNA-PK complex activity in breast cancer cells (MDA-465 and MDA-468). Consequently, the peptide treated cells exhibited poor to no DNA repair, and became highly sensitive to irradiation or chemotherapy drugs. The growth of breast cancer cells was also inhibited. These results demonstrate the possibility of synthetic peptide to apply breast cancer therapy to induce apoptosis of cancer cells.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.7
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• pp.2793-2800
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• 2015

In molecular-targeted cancer therapy, acquired resistance to gemcitabine is a major clinical problem that reduces its effectiveness, resulting in recurrence and metastasis of cancers. In spite of great efforts to reveal the overall mechanism of acquired gemcitabine resistance, no definitive genetic factors have been identified that are absolutely responsible for the resistance process. Therefore, we performed a cross-platform meta-analysis of three publically available microarray datasets for cancer cell lines with acquired gemcitabine resistance, using the R-based RankProd algorithm, and were able to identify a total of 158 differentially expressed genes (DEGs; 76 up- and 82 down-regulated) that are potentially involved in acquired resistance to gemcitabine. Indeed, the top 20 up- and down-regulated DEGs are largely associated with a common process of carcinogenesis in many cells. For the top 50 up- and down-regulated DEGs, we conducted integrated analyses of a gene regulatory network, a gene co-expression network, and a protein-protein interaction network. The identified DEGs were functionally enriched via Gene Ontology hierarchy and Kyoto Encyclopedia of Genes and Genomes pathway analyses. By systemic combinational analysis of the three molecular networks, we could condense the total number of DEGs to final seven genes. Notably, GJA1, LEF1, and CCND2 were contained within the lists of the top 20 up- or down-regulated DEGs. Our study represents a comprehensive overview of the gene expression patterns associated with acquired gemcitabine resistance and theoretical support for further clinical therapeutic studies.