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Biomedical subjects

S B Han

Publications and source records attributed to S B Han.

At least 19 recordsLinked to original sources
PubMed2004

Bioequivalence of a prednisolone tablet administered as a single oral dose in healthy male volunteers.

OBJECTIVE: A bioequivalence study ofprednisolone as Nisolone (test) tablets versus Delta-Cortef (reference) tablets was conducted. PATIENTS AND METHODS: Eighteen healthy male Korean volunteers received both 20 mg formulations of prednisolone in this 2 x 2 crossover study with a 1-week washout period between the doses. Plasma concentrations of prednisolone were monitored over a period of 12 hours after the administration using high-performance liquid chromatography. The AUC (area under the plasma concentration-time curve from time zero to infinity) and AUCt (area under the plasma concentration-time curve from time zero to the last sampling time) were calculated using the trapezoidal rule-extrapolation method. The Cmax (maximum plasma drug concentration) and t(max) (time to reach Cmax) were compiled from the plasma concentration-time data. Analysis of variance was carried out using logarithmically transformed AUC, AUCt and Cmax and untransformed t(max). RESULTS: The geometric mean of AUCt was 1,786 ng/ml x h (test medication) and 1,787 ng/ml xh (reference medication). A Cmax of 409 ng/ml and 404 ng/ml was achieved for the test and the reference medication, respectively. Point estimates and 90% confidence intervals for AUCt (parametric) and Cmax (parametric) were 0.989 (0.942 approximately 1.039) and 1.013 (0.934 approximately 1.100), respectively. These results satisfy the bioequivalence criteria of the European Committee for Proprietary Medicinal Products and the US Food and Drug Administration Guidelines. The corresponding value of t(max) was -0.221 (-0.415 approximately 0.000). CONCLUSION: The 2 medications of prednisolone examined are bioequivalent and, thus, may be prescribed interchangeably.

Administration, Oral↗
PubMed2003

Characterization of B cell membrane receptors of polysaccharide isolated from the root of Acanthopanax koreanum.

We investigated the immunomodulatory activity of polysaccharide isolated from the root of Acanthopanax koreanum (AK) at the cellular level. AK directly increased B cell proliferation and antibody production, but did not affect the expression of IL-2, IFN-gamma or IL-4 by T cells, or T cell proliferation in vitro. Since AK cannot penetrate cells due to its large molecular mass, B cell activation may be caused by the surface binding of AK to B cell-specific receptors. The role of TLR4 as an AK receptor was shown by the fact that AK activity in B cells from C3H/HeJ mice, which are known to have a defective Toll-like receptor (TLR)-4, was found to be reduced compared with that in control cells from C3H/HeN mice. AK activity was also reduced by antibodies blocking TLR2, TLR4, CD19 or CD79b, but not by an antibody blocking CD38, which suggests AK receptor profiling in B cells. Two main differences between AK and lipopolysaccharide (LPS) were observed. First, LPS activity was inhibited by antibodies to either TLR2 or TLR4, but not by antibodies to CD19, CD79b or CD38. Another was that LPS-induced B cell proliferation was inhibited by polymyxin B (PMB), a specific inhibitor of LPS, whereas AK activity was not affected. Taken together, our results demonstrate that AK directly activates B cells, but not T cells, and suggest that AK has a broader receptor profile than LPS in B cells.

Adjuvants, Immunologic↗
PubMed2003

Toll-like receptor-mediated activation of B cells and macrophages by polysaccharide isolated from cell culture of Acanthopanax senticosus.

We investigated the mechanism of the immunomodulatory action of polysaccharide (ASP) isolated from a cell culture of Acanthopanax senticosus. ASP was found to directly increase the proliferation and differentiation of B cells, and the cytokine production of macrophage, but not the proliferation and cytokine production of T cells. Since ASP cannot penetrate the cell membrane due to its large molecular mass, such cellular activation may be caused by the surface binding of ASP to receptors expressed on B cells and macrophages. The possibility that TLRs, which are known to be involved in immune-related responses, may be the receptor(s) of ASP was investigated. The immunomodulating activities of ASP on the B cells and macrophages of C3H/HeJ mice, expressing a defective toll-like receptor (TLR)-4, were decreased versus the corresponding cells from C3H/HeN mice. In addition, the activities of ASP on B cells and macrophages were significantly reduced by treating the cells with antibodies to TLR4 and TLR2 prior to ASP, suggesting that both of them are the possible receptors of ASP. The ligation of TLRs induced by ASP was able to activate mitogen-activated protein kinases (MAPKs), such as Erk1/2, p38 and JNK, and the transcription factor NF-kappaB. Although ASP was shown to activate the TLR signaling cascades in the same manner as lipopolysaccharide (LPS), these two could be differentiated by the finding that polymyxin B (PMB), a specific inhibitor of LPS, did not significantly affect the activities of ASP on B cells and macrophages. Taken together, our results demonstrate that ASP, isolated from a cell culture of A. senticosus, activates B cells and macrophages by interacting with TLRs and leading to the subsequent activation of mitogen-activated protein kinases and NF-kappaB.

Adjuvants, Immunologic↗
PubMed2001

Liquid chromatographic determination of less polar ginsenosides in processed ginseng.

Reversed-phase LC with an evaporative light scattering detector (ELSD) is used for the determination of less polar ginsenosides in processed ginseng. These ginsenosides include ginsenosides F4, Rg3, Rg5, Rg6, Rk1, Rk3, Rs3, Rs4, and Rs5. The method used a C18-bonded silica column with a CH3CN/H2O/CH3COOH gradient elution. (20R) and (20S) epimers and geometric isomers at the C-20 position of ginsenosides, which are not generally separated by amino columns, were now clearly separated.

Chromatography, Liquid↗
PubMed2001

Tissue-engineered growth of bone by marrow cell transplantation using porous calcium metaphosphate matrices.

In this study we investigated not only osteoblastic cell proliferation and differentiation on the surface of calcium metaphosphate (CMP) matrices in vitro but also bone formation by ectopic implantation of these cell-matrix constructs in athymic mice in vivo. Interconnected porous CMP matrices with pores 200 microm in size were prepared to use as scaffolds for rat-marrow stromal-cell attachment. Cell-matrix constructs were cultured in vitro, and cell proliferation and ALPase activities were monitored for 56 days. In addition to their being cultured in vitro, cell-matrix constructs were implanted into subcutaneous sites of athymic mice. In vitro these porous CMP matrices supported the proliferation of osteoblastic cells as well as their differentiation, as indicated by high ALPase activity. In vivo the transplanted marrow cells gave rise to bone tissues in the pores of the CMP matrices. A small amount of woven bone formation was detected first at 4 weeks; osteogenesis progressed vigorously with time, and thick lamellar bones that had been remodeled were observed at 12 weeks. These findings demonstrate the potential for using a porous CMP matrix as a biodegradable scaffold ex vivo along with attached marrow-derived mesenchymal cells for transplantation into a site for bone regeneration in vivo.

Alkaline Phosphatase↗
PubMed2001

Activation of mitogen-activated protein kinase pathways by angelan in murine macrophages.

In our previous studies, we showed that angelan, a polysaccharide purified from Angelica gigas Nakai, specifically activated macrophages to induce cytokines including inducible nitric oxide synthase (iNOS) which has strong anti-tumor activities [Immunopharmacology, 1999; 43: 1.]. In the present study, we investigated the intracellular signal transduction pathways involved in the angelan-induced iNOS synthesis by murine macrophages. Protein tyrosine phosphorylation was induced within 5 min by angelan, and the blocking of protein tyrosine kinases (PTKs) inhibited down-stream pathways leading to iNOS production in response to angelan. Treament of RAW 264.7 cells with angelan resulted in significant activation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) and p38, while stress-activated protein kinase/c-Jun NH2 terminal kinase (SAPK/JNK) was not activated by angelan. The specific p38 inhibitor SB203580 abrogated the angelan-induced iNOS synthesis, whereas the selective mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase 1 (MEK-1) inhibitor PD98059 did not affect the iNOS induction. In conclusion, we demonstrate that PTK and p38 MAPK activation are required to transduce signals leading to iNOS expression in angelan-stimulated murine macrophages.

Animals↗
PubMed2001

Polysaccharide isolated from the radix of Platycodon grandiflorum selectively activates B cells and macrophages but not T cells.

Many polysaccharides isolated from plants are considered to be biological response modifiers and have been shown to enhance various immune responses in vivo and in vitro. Here, we demonstrate that polysaccharide isolated from the radix of Platycodon grandiflorum (PG) has a unique mode of immunostimulation with regard to its cell-type specificity. PG was found to markedly increase polyclonal IgM antibody production and the proliferation of B cells, and to activate iNOS transcription and NO production in macrophages. Moreover, the intraperitoneal administration of PG in mice resulted in increased IgM antibody production in B cells, which were immunized by using T-dependent antigen sheep red blood cells (sRBCs). However, PG did not affect the proliferation of T cells, the IL-2 expression of Th1 cells, or the IL-4 expression of Th2 cells. Although PG and lipopolysaccharide (LPS) had a similar mode of action in B cells and macrophages, they were differentiated by the fact that PG-induced cellular activation was not inhibited by polymyxin B, a specific inhibitor of LPS. Anti-CD19 or anti-CD79b antibody blocked B cell proliferation and anti-CD14 or anti-CD 11b antibody decreased macrophage NO production, indicating the possible cellular binding sites of PG. Our results demonstrate that PG is a specific activator of B cells and macrophages but not of T cells, and suggest that PG is quite distinct from other well-known immunostimulants, such as lentinan and schizophyllan, which mainly act upon macrophages and T cells.

Animals↗
PubMed2001

The effect of aspirin and prostaglandin E(1) on the patency of microvascular anastomosis in the rats.

The purpose of this study was to evaluate the effect of oral prostaglandin E(1)(PGE(1)) on the patency of the microvascular anastomosis of the carotid artery in rat. A total of 48 rats were used, and divided into three groups. The first group (A) was used as a control with no medical agent being used after anastomosis, the second group (B) was medicated with aspirin, and the third group (C) was medicated with oral PGE(1). In each group, four rats were sacrificed serially on every post-operative 3, 5, 10 and 15 days after arterial anastomosis. Patency and histologic evaluations at the anastomotic site were observed. The results revealed that the PGE(1) therapied group showed highest patency rate (100%), lesser formation of mural thrombosis, and also minimal changes in the intimal hyperplasia and medial fibrosis. From these findings, we could conclude that PGE(1) has superior effect on maintaining the patency after microvascular surgery.

Administration, Oral↗
PubMed2001

Polychlorinated biphenyls activate caspase-3-like death protease in vitro but not in vivo.

We prove here that serum albumin inhibits apoptosis induced by polychlorinated biphenyls (PCBs), confirming that serum albumin binds to PCB, and that the albumin-PCB complexes inhibit apoptosis in HL-60 cells. We found that PCB (50 microM) increased the activity of caspase-3-like protease when HL-60 cells, as well as splenocytes, were cultured in "serum-free medium." Benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (Z-VAD-fmk) inhibited apoptosis in cells cultured in the serum-free medium containing 50 microM PCB. To elucidate whether or not PCBs induce apoptosis in vivo, we examined apoptosis of splenocytes by administering PCB to ICR mice (100, 500, 1000 mg x kg(-1) x d(-1)) for 5 d and characterizing splenocytes. Interestingly, splenocytes treated with PCB did not show any changes characteristic of apoptosis. These results demonstrate that PCB activates the caspase-3-like death protease in vitro in serum-free medium, but does not induce apoptosis of splenocytes in vivo, suggesting that blood serum may mask the apoptosis induced by PCB.

Animals↗
PubMed2001

Prodigiosin blocks T cell activation by inhibiting interleukin-2Ralpha expression and delays progression of autoimmune diabetes and collagen-induced arthritis.

Prodigiosin (PDG) was previously reported to be a T cell-specific immunosuppressant. Here we describe the mechanism of action of PDG in T cells and the effect of PDG on autoimmune diseases. PDG selectively suppresses concanavalin A (Con A)-induced T cell proliferation, but has little effect on lipopolysaccharide-induced proliferation of B cells and nitric oxide production of macrophages. Although PDG does not block interleukin (IL)-2 production, it efficiently inhibits interleukin-2 receptor alpha-chain (IL-2Ralpha) expression, and this results in a disruption of the IL-2/IL-2R signaling pathway, on which a great part of the regulation of T cell activation depends. PDG blocks T cell differentiation into effector helper T cells secreting interferon-gamma and IL-4 as well as into effector cytotoxic T lymphocytes expressing perforin, which is at least in part resulting from inhibition of the IL-2/IL-2R signaling. PDG indirectly blocks signal transducer and activator of transcription activation by inhibiting cytokine signalings in Con A-activated T cells, although it does not inhibit the activation of nuclear factor-kappaB, nuclear factor of activated T cells, and activator protein-1. As direct evidence of immunosuppression in vivo, we show that PDG markedly reduced blood glucose levels and cellular infiltration into the pancreatic islets in nonobese diabetic mice, and that it also delays the onset of collagen-induced arthritis in DBA/1 mice. In conclusion, our results demonstrate that PDG has a unique mode of action, namely, that it blocks T cell activation by inhibiting primarily IL-2Ralpha expression in the IL-2/IL-2R signaling, and show that this compound represents a promising immunosuppressant candidate for the treatment of autoimmune diseases.

Animals↗
PubMed2000

Immunomodulating activity of a polysaccharide isolated from Mori Cortex Radicis.

The immunomodulating activity of a polysaccharide isolated from Morus alba (PMA) root bark was examined in murine splenic lymphocytes. PMA enhanced proliferation of splenic lymphocytes in a synergistic manner in the presence of mitogens. However, PMA suppressed primary IgM antibody production from B cells, which was activated with lipopolysaccharide, a polyclonal activator, or immunized with a T-cell dependent antigen sheep red blood cells. Our observations showed that the immunomodulating activity of PMA increased lymphocyte proliferation and that PMA decreased antibody production from B cells, which was distinct from those of other plant-originated polysaccharides.

Adjuvants, Immunologic↗
PubMed2000

Effect of extracellular cations on the chemotherapeutic efficacy of anticancer drugs.

Cancer development and the efficiency of chemotherapy relies on the patients calcium-related pathological status such as hyper- or hypocalcemia. In the present study, we investigated the effect of extracellular cations such as calcium and magnesium on the therapeutic efficacy of antitumor drugs. The analytic parameters used were cellular drug uptake/excretion and the chemosensitivity of the human breast cancer cell lines, MCF7 and MCF7/ADR. Both calcium and magnesium ions decreased the membrane permeability of cancer cells, which was determined by cell size analysis. These divalent ions also lowered the drug uptake and the cytoplasmic levels of rhodamine 123 and adriamycin, suggesting that they might interfere with the diffusion of these drugs by modifying the physical properties of the cytoplasmic membrane. The acute cytotoxicity of adriamycin after a short period of incubation correlated with changes in its cytoplasmic level. Our results indicate that these extracellular cations might play an important role in the therapeutic activities of anticancer drugs in cancer patients. These results also provide insight a new aspect of chemotherapy, because they suggest that the therapeutic doses of anti-cancer drugs should be modified in cancer-bearing patients presenting with abnormal blood calcium levels.

Antineoplastic Agents↗
PubMed2000

Differential activation of murine macrophages by angelan and LPS.

In our previous studies, we showed that angelan, a polysaccharide purified from Angelica gigas Nakai, is a potent LPS-mimetic in murine macrophages [Jeon, Y.J., Han, S.B., Ahn, K.S., Kim, H.M., 1999. Activation of NF-kB/Rel in angelan-stimulated macrophages. Immunopharmacology 43, 1-9]. Angelan stimulates murine macrophage to produce cytokines including iNOS and activate NF-kappaB/Rel. In the present study, we investigated the role of CD14 and complement receptor type 3 (CR3) in mediating NO production and NF-kappaB/Rel activation induced by angelan and LPS. Three major differences between angelan and LPS were observed. First, angelan does not require serum proteins for NO response and NF-kappaB/Rel activation, while the activation by LPS requires serum proteins. Second, blocking of either CD14 or CR3 decreased angelan-induced NO response, while LPS-mediated NO production was inhibited by anti-CD14 mAb only. Third, angelan induced strong NF-kappaB/Rel and slight AP-1 DNA binding, whereas LPS potently activated both NF-kappaB/Rel and AP-1. Both angelan and LPS degraded IkappaB proteins and subsequently induced the mobilization of NF-kappaB/Rel proteins (p65, c-rel and p50) into nucleus. This suggests that macrophages display a common signaling machinery leading to the NF-kappaB/Rel activation in response to different stimulants. In conclusion, angelan and LPS use the membrane receptor CD14 and CR3 differentially for signaling NF-kappaB/Rel activation and NO production.

Acute-Phase Proteins↗
PubMed2000

Steaming of ginseng at high temperature enhances biological activity.

The present study was performed to evaluate the effect of steaming ginseng at a temperature over 100 degrees C on its chemical constituents and biological activities. Raw ginseng was steamed at 100, 110, and 120 degrees C for 2 h using an autoclave. The ginseng steamed at 120 degrees C was more potent in its ability to induce endothelium-dependent relaxation. Steaming the raw ginseng at 120 degrees C also remarkably increased the radical-scavenging activity. Ginsenosides F(4), Rg(3), and Rg(5), which were not present in raw ginseng, were produced after steaming. Ginsenosides Rg(3) and Rg(5) were the most abundant ginsenosides in the ginseng steamed at 120 degrees C, accounting for 39% and 19% of all ginsenosides, respectively.

Chromatography, High Pressure Liquid↗
PubMed2000

Tissue engineered bone formation using chitosan/tricalcium phosphate sponges.

BACKGROUND: Chitosan is a biodegradable natural polymer that has been shown to improve wound healing. This study aimed to develop chitosan/tricalcium phosphate (TCP) sponges as tissue engineering scaffolds for bone formation by three-dimensional osteoblast culture. METHODS: The sponges were prepared by freeze-drying and cross-linking a mixture of chitosan solution with TCP. Fetal rat calvarial osteoblastic cells were isolated, cultured, and seeded into the sponges. The cell-sponge constructs were cultured for 56 days. Cell proliferation, alkaline phosphatase (ALPase) activity, and calcium deposition in the cell-sponge constructs were measured at 1, 7, 14, 28, and 56 days. Histologic examination was performed with light microscopy and scanning electron microscopy. RESULTS: Chitosan/TCP sponges supported the proliferation of osteoblastic cells as well as their differentiation as indicated by high ALPase activities and deposition of mineralized matrices by the cells. Light and scanning electron microscopic examination indicated that seeded osteoblastic cells were well attached to sponge matrices and proliferated in a multi-layer fashion. Small bone-like spicules were observed on the sponge matrix at 14 days. Seeded cells appeared to be embedded in the newly formed tissue matrix, which is characteristic of the osteoblast differentiation and their progression into osteocytic cells. The amount of mineralized tissue formed in the sponge at 56 days was significant. CONCLUSIONS: These results suggest that the chitosan/TCP sponge is a feasible tool as a scaffolding material to grow osteoblast in a three-dimensional structure for transplantation into a site for bone regeneration.

Absorbable Implants↗
PubMed2000

The bone regenerative effect of platelet-derived growth factor-BB delivered with a chitosan/tricalcium phosphate sponge carrier.

BACKGROUND: In order to achieve optimal effects, growth factors including platelet-derived growth factor (PDGF) should be delivered with a biodegradable carrier that will release therapeutic concentrations over a sufficient length of time. The purpose of this study was to evaluate the bone regenerative effect of PDGF-BB delivered with a chitosan/tricalcium phosphate (TCP) sponge carrier in a rat calvarial defect model. METHODS: The PDGF-BB-loaded chitosan/TCP sponge carrier was fabricated by freeze-drying a mixture of chitosan solution and TCP powder and soaking in a PDGF-BB solution. The release kinetics of PDGF-BB loaded onto the sponge were measured in vitro with 125I-labeled PDGF-BB. Chitosan/TCP sponges with and without PDGF-BB were implanted into 8 mm calvarial defects in rats. Rats were sacrificed at 2 and 4 weeks following implantation, and histologic and histomorphometrical examinations were performed. RESULTS: In vitro evaluation demonstrated that an effective therapeutic concentration of PDGF-BB following a high initial burst release was maintained throughout the examination period. In the histologic examination, the chitosan/TCP sponge carrier promoted osseous healing of the rat calvarial defects as compared to controls. The addition of PDGF-BB to the carrier further enhanced bone regeneration. Evidence of the degraded sponge matrix was observed mingled within the newly formed bone without connective tissue encapsulation. CONCLUSIONS: The results of this study support the use of chitosan/TCP sponges as a delivery system for growth factors and demonstrate that PDGF-BB loaded onto chitosan/TCP sponge carriers has an osteogenic effect on bone regeneration in vivo.

Absorbable Implants↗