• Investigative Magnetic Resonance Imaging
• /
• v.3 no.2
• /
• pp.159-166
• /
• 1999

Purpose : To evaluate the effect of rotational correlation time (${\tau}_R$) and the possible related changes of other parameters, ${\tau}_M,{\;}{\tau}_S,{\;}and{\;}(\tau}_V$ of gadolinium (Gd) chelate on T1 relaxation enhancement in two pool model. Materials and Methods : The NMRD (Nuclear Magnetic Relaxation Dispersion) profiles were simulated from 0.02 MHz to 800 MHz proton Larmor frequency for different values of rotational correlation times based on Solomon-Bloembergen equation for inner-sphere relaxation enhancement. To include both unbound pool (pool A) and bound pool (pool B), the relaxivity was divided by contribution from unbound pool and bound pool. The rotational correlation time for pool A was fixed at the value of 0.1 ns, which is a typical value for low molecular weight complexes such as Gd-DTPA in solution and ${\tau}_R$ for pool B was changed from 0.1 ns to 20 ns to allow the slower rotation by binding to macromolecule. The fractional factor of was also adjusted from 0 to 1.0 to simulate different binding ratios to macromolecule. Since the binding of Gd-chelate to macromolecule cab alter the electronic environment of Gd ion and also the degree of bulk water access to hydration site of Gd-chelate, the effects of these parameters were also included. Results : The result shows that low field profiles, ranged from 0.02 to 40 MHz, and dominated by contribution from bound pool, which is bound to macromolecule regardless of binding ratios. In addition, as more Gd-chelate bound to macromolecule, sharp increase of relaxivity at higher field occurs. The NMRD profiles for different values of ${\tau}_S$ show the enormous increase of low field profile whereas relaxivity at high field is not affected by ${\tau}_S$. On the other hand, the change in ${\tau}$V does not affect low field profile but strongly in fluences on both inflection fie이 and the maximum relaxivity value. The results shows a fluences on both inflection field and the maximum relaxivity value. The results shows a parabolic dependence of relaxivity on ${\tau}_M$. Conclusion : Binding of Gd-chelate to a macromolecule causes slower rotational tumbling of Gd-chelate and would result in relaxation enhancement, especially in clinical imaging field. However, binding to macromolecule can change water enchange rate (${\tau}_M$) and electronic relaxation ($T_le$) vis structural deformation of electron environment and the access of bulk water to hydration site of metal-chelate. The clinical utilities of Gd-chelate bound to macromolecule are the less dose requirement, the tissue specificity, and the better perfusion and intravascular agents.

• Archives of Pharmacal Research
• /
• v.29 no.10
• /
• pp.928-933
• /
• 2006

Percutaneous delivery of NSAIDs has advantages of avoiding hepatic first pass effect and delivering the drug for extended period of time at a sustained, concentrated level at the inflammation site that mainly acts at the joint and the related regions. To develop the new topical formulations of pranoprofen that have suitable bioadhesion, the gel was formulated using hydroxypropyl methylcellulose (HPMC) and poloxamer 407. The effects of temperature on drug release was performed at $32^{\circ}C$, $37^{\circ}C$ and $42^{\circ}C$ according to drug concentration of 0.04%, 0.08%, 0.12%, 0.16%, and 0.2% (w/w) using synthetic cellulose membrane at $37{\pm}0.5^{\circ}C$. The increase of temperature showed the increased drug release. The activation energy (Ea), which were calculated from the slope of lop P versus 1000/T plots was 11.22 kcal/ mol for 0.04%, 10.79 kcal/mol for 0.08%, 10.41 kcal/mol for 0.12% and 8.88 kcal/mol for 0.16% loading dose from the pranoprofen gel. To increase the drug permeation, some kinds of penetration enhancers such as the ethylene glycols, the propylene glycols, the glycerides, the non-ionic surfactants and the fatty acids were incorporated in the gel formulation. Among the various enhancers used, propylene glycol mono laurate showed the highest enhancing effects with the enhancement factor of 2.74. The results of this study suggest that development of topical gel formulation of pranoprofen containing an enhancer is feasible.

• Korean Journal of Radiology
• /
• v.21 no.1
• /
• pp.58-67
• /
• 2020

Objective: Third-generation dual-source computed tomography (3rd-DSCT) allows dynamic myocardial CT perfusion imaging (dynamic CTP) with a 10.5-cm z-axis coverage. Although the increased radiation exposure associated with the 50% wider scan range compared to second-generation DSCT (2nd-DSCT) may be suppressed by using a tube voltage of 70 kV, it remains unclear whether image quality and the ability to quantify myocardial blood flow (MBF) can be maintained under these conditions. This study aimed to compare the image quality, estimated MBF, and radiation dose of dynamic CTP between 2ndDSCT and 3rd-DSCT and to evaluate whether a 10.5-cm coverage is suitable for dynamic CTP. Materials and Methods: We retrospectively analyzed 107 patients who underwent dynamic CTP using 2nd-DSCT at 80 kV (n = 54) or 3rd-DSCT at 70 kV (n = 53). Image quality, estimated MBF, radiation dose, and coverage of left ventricular (LV) myocardium were compared. Results: No significant differences were observed between 3rd-DSCT and 2nd-DSCT in contrast-to-noise ratio (37.4 ± 11.4 vs. 35.5 ± 11.2, p = 0.396). Effective radiation dose was lower with 3rd-DSCT (3.97 ± 0.92 mSv with a conversion factor of 0.017 mSv/mGy∙cm) compared to 2nd-DSCT (5.49 ± 1.36 mSv, p < 0.001). Incomplete coverage was more frequent with 2nd-DSCT than with 3rd-DSCT (1.9% [1/53] vs. 56% [30/54], p < 0.001). In propensity score-matched cohorts, MBF was comparable between 3rd-DSCT and 2nd-DSCT in non-ischemic (146.2 ± 26.5 vs. 157.5 ± 34.9 mL/min/100 g, p = 0.137) as well as ischemic myocardium (92.7 ± 21.1 vs. 90.9 ± 29.7 mL/min/100 g, p = 0.876). Conclusion: The radiation increase inherent to the widened z-axis coverage in 3rd-DSCT can be balanced by using a tube voltage of 70 kV without compromising image quality or MBF quantification. In dynamic CTP, a z-axis coverage of 10.5 cm is sufficient to achieve complete coverage of the LV myocardium in most patients.

• Journal of Ginseng Research
• /
• v.39 no.3
• /
• pp.238-242
• /
• 2015

Background: Panax ginseng has been used to prolong longevity and is believed to be useful for improving skin complexion. Ginsenosides are the most active components isolated from ginseng, and ginsenoside Rg3 (G-Rg3) in particular has been demonstrated to possess antioxidative, antitumorigenic, and anti-inflammatory properties. The aim of this study was to examine the ability of G-Rg3 to inhibit melanogenesis. Methods: The effects of G-Rg3 on melanin contents and the protein levels of tyrosinase, microphthalmia-associated transcription factor (MITF), and tyrosinase-related protein 1 (TRP1) were evaluated. Melanogenesis-regulating signaling molecules such as Akt and extracellular signal-regulated kinase (ERK) were also examined to explore G-Rg3-induced antimelanogenic mechanisms. Results: G-Rg3 was found to significantly inhibit the synthesis of melanin in normal human epidermal melanocytes and B16F10 cells in a dose-dependent manner. The activity of cellular tyrosinase and the expression of MITF, tyrosinase, and TRP1 were all reduced, whereas ERK was strongly activated. PD98059 (a specific inhibitor of ERK) attenuated the G-Rg3-induced inhibition of melanin synthesis and tyrosinase activity. Conclusion: Taken together, these results showed that G-Rg3 induces the activation of ERK, which accounts for its antimelanogenic effects. G-Rg3 may be a promising safe skin-whitening agent, adding to the long list of uses of P. ginseng for the enhancement of skin beauty.

• Restorative Dentistry and Endodontics
• /
• v.24 no.1
• /
• pp.187-199
• /
• 1999

Bone remodeling is characterized by the continuing processes of osteoblast-mediated bone formation and osteoclast-mediated bone resorption. Bone metabolism is tightly regulated at the local level by networks of hormones, cytokines, and other factors. In pathological conditions of bone remodeling, including osteoporosis and periodontal diseases, inflammatory cytokines and local mediators are responsible for enhancement of osteoclast resorption and inhibition of repair at the sites of bone resorption. TNF-${\alpha}$ is a pleiotropic hormone with actions on the differentiation, growth, and functional activities of normal and malignant cells from numerous tissues. TNF-${\alpha}$ has been proposed as a local mediator of the control of bone turnover in situations of chronic inflammation, and it has been assumed that the local source of TNF-${\alpha}$ is the monocyte in the adjacent bone marrow or the local circulation. TNF-${\alpha}$ is a potent inducer of bone resorption. TNF-${\alpha}$ is known to induce the activation of apoptotic signaling pathway, which leads to the apoptosis of bone cells. We demonstrated that treatment of murine osteoblastic MC3T3E1 cells with TNF-${\alpha}$ decreases proliferation as well as alkaline phosphatase (ALP) activity in a dose depenent manner. In addition, TNF-${\alpha}$ increases osteoclast-like cell formation in $1{\alpha}$, 25(OH)2D3 or PGE2-treated bone marrow cell culture. When cells were cultured in TNF-${\alpha}$ free ${\alpha}$-MEM, this inhibitory effect of ALP activity was reversible up to 10 ng/ml TNF-${\alpha}$, in contrast, at the 20 ng/ml TNF-${\alpha}$, irreversible. In this concentration, TNF-${\alpha}$ may induce apoptosis in MC3T3E1 cells. In this study, TNF-${\alpha}$ induces apoptosis resulting in chromosomal DNA fragmentation, preceded by JNK/SAPKs and caspase-3 activation. Our present results show that JNK/SAPKs and caspase-3 are activated by TNF-${\alpha}$, suggesting that the JNK/SAPKs and caspase-3 participate in the bone resorption, associated with apoptosis.

• Journal of Korean Neurosurgical Society
• /
• v.42 no.2
• /
• pp.92-96
• /
• 2007

Objective : The authors have speculated that metastatic brain lesions from renal cell carcinoma (RCC) show diverse radiological patterns and tumor responses after Gamma knife surgery (GKS), and have hypothesized that these can be predicted from tumor radiological characteristics. The goal of the current study was to identify the radiological characteristics of RCC brain metastases and the predictors of initial radiosurgical response after GKS. Methods : A retrospective analysis was performed on 48 lesions in 18 patients with RCC brain metastasis treated by GKS. The radiological characteristics of these lesions in magnetic resonance images (MRI) were classified into 3 categories according to enhancement patterns in T1-weighted images and signal intensity characteristics in T2-weighted images. Responses to GKS were analyzed according to these categories, and in addition, other potential predictive factors were also evaluated. Results : MRI findings in the three categories were diverse, though numbers of the lesion were comparable. At 2-month MRI follow-ups after GKS, response rate was 54% and the local tumor control rate 83%. T2 signal intensity was found to be the principal predictive factor of response to GKS, namely negative predictive factor. Other variables such as age, sex, tumor volume, dose, duration from initial diagnosis to GKS, and previous systemic therapies failed to show significant relationships with treatment response by multivariate analysis. Conclusion : Careful evaluation of the radiological characteristics of brain metastases from RCC is important prior to GKS because MRI heterogeneity has predictive value in terms of determining initial tumor response.

• Biomolecules & Therapeutics
• /
• v.27 no.1
• /
• pp.117-125
• /
• 2019

Mebendazole (MBZ), a microtubule depolymerizing drug commonly used for the treatment of helminthic infections, has recently been noted as a repositioning candidate for angiogenesis inhibition and cancer therapy. However, the definite anti-angiogenic mechanism of MBZ remains unclear. In this study, we explored the inhibitory mechanism of MBZ in endothelial cells (ECs) and developed a novel strategy to improve its anti-angiogenic therapy. Treatment of ECs with MBZ led to inhibition of EC proliferation in a dose-dependent manner in several culture conditions in the presence of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) or FBS, without selectivity of growth factors, although MBZ is known to inhibit VEGF receptor 2 kinase. Furthermore, MBZ inhibited EC migration and tube formation induced by either VEGF or bFGF. However, unexpectedly, treatment of MBZ did not affect FAK and ERK1/2 phosphorylation induced by these factors. Treatment with MBZ induced shrinking of ECs and caused G2-M arrest and apoptosis with an increased Sub-G1 fraction. In addition, increased levels of nuclear fragmentation, p53 expression, and active form of caspase 3 were observed. The marked induction of autophagy by MBZ was also noted. Interestingly, inhibition of autophagy through knocking down of Beclin1 or ATG5/7, or treatment with autophagy inhibitors such as 3-methyladenine and chloroquine resulted in marked enhancement of anti-proliferative and pro-apoptotic effects of MBZ in ECs. Consequently, we suggest that MBZ induces autophagy in ECs and that protective autophagy can be a novel target for enhancing the anti-angiogenic efficacy of MBZ in cancer treatment.

• Radiation Oncology Journal
• /
• v.17 no.3
• /
• pp.256-260
• /
• 1999

Purpose : An investigation has been carried out on the factors which affect the response reading of thermoluminescent dosimeters (TLD-100) loaded with thin material in high energy Photon. The aim of the study was to assess the energy response of TLD-100 to the therapeutic ranges of photon beam. Materials and Methods : In this technique, TLD-100 (abbreviated as TLD) chips and three different thin material (Tin, Gold, and Tissue equivalent plastic plate) which mounted on the TLD chip were used in the clinical photon beam. The thickness of each metal plates was 0.1 mm and TE plastic plate was 1 mm thick. These compared with the photon energy dependence of the sensitivities of TLD (normal chip), TLD loaded with Tin or Gold plate, for the photon energy range 6 MV to 15 MV, which was of interest in radiotherapy. Results : The enhancement of surface dose in the TLD with metal plate was clearly detected. The TLD chips with a Gold plate was found to larger response by a factor of 1.83 in 10 MV photon beam with respect to normal chip. The sensitivity of TLD loaded with Tin was less than that for normal TLD and TLD loaded with Gold. The relative sensitivity of TLD loaded with metal has little energy dependence. Conclusion : The good stability and linearity with respect to monitor units of TLD loaded with metal were demonstrated by relative measurements in high energy Photon ($6\~15$ MV) beams. The TLD laminated with metals embedded system in solid water phantom is a suitable detector for relative dose measurements in a small beam size and surface dose.

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

• Biomolecules & Therapeutics
• /
• v.13 no.3
• /
• pp.174-180
• /
• 2005

Antigen presenting cells (APCs), dendritic cells (DCs) and macrophages, playa critical role not only in the initiation of immune responses, but also in the induction of immune tolerance. In an effort to regulate immune responses through the modulation of APC function, we searched for and characterized APC function modulators from natural products. Bifidobacterium pseudocatenulatum SPM1204 (SPM1204) isolated from feces of healthy Korean in the age of 20s was used in this experiment. DCs and macrophages were cultured in the presence of supernatants of SPM 1204 and then examined for their activities for the presentation exogenous antigen in association with major histocompatibility complexes (MHC) and macrophage activation. SPM1204 increased class I MHC-restricted presentation of exogenous antigen (cross-presentation) in a DC cell line, DC2.4 cells. The RAW 264.7 cell line was used to test the nonspecific effect of immune reinforcement of SPM1204 as a source of biological regulating modulator for the macrophage activation, include nitric oxide (NO) production and cytokine production. Results showed that the production of NO, tumor necrosis factor (TNF)-$\alpha$, interleukin 1 (IL-1)-$\beta$ and morphological changes in macrophages were largely affected by SPM1204 in a dose-dependent manner. Our results demonstrated that SPM1204 promote cross-presentation of dendritic cells as well as the induction of NO, TNF-$\alpha$ production, and activation of macrophage.