Impact of lattice versus solid structure of 3D-printed multiroot dental implants using Ti-6Al-4V: a preclinical pilot study.

PURPOSE: Various studies have investigated 3-dimensional (3D)-printed implants using Ti-6Al-4V powder; however, multi-root 3D-printed implants have not been fully investigated. The purpose of this study was to explore the stability of multirooted 3D-printed implants with lattice and solid structures. The secondary outcomes were comparisons between the 2 types of 3D-printed implants in micro-computed tomographic and histological analyses. METHODS: Lattice- and solid-type 3D-printed implants for the left and right mandibular third premolars in beagle dogs were fabricated. Four implants in each group were placed immediately following tooth extraction. Implant stability measurement and periapical X-rays were performed every 2 weeks for 12 weeks. Peri-implant bone volume/tissue volume (BV/TV) and bone mineral density (BMD) were measured by micro-computed tomography. Bone-to-implant contact (BIC) and bone area fraction occupancy (BAFO) were measured in histomorphometric analyses. RESULTS: All 4 lattice-type 3D-printed implants survived. Three solid-type 3D-printed implants were removed before the planned sacrifice date due to implant mobility. A slight, gradual increase in implant stability values from implant surgery to 4 weeks after surgery was observed in the lattice-type 3D-printed implants. The marginal bone change of the surviving solid-type 3D-printed implant was approximately 5 mm, whereas the value was approximately 2 mm in the lattice-type 3D-printed implants. BV/TV and BMD in the lattice type 3D-printed implants were similar to those in the surviving solid-type implant. However, BIC and BAFO were lower in the surviving solid-type 3D-printed implant than in the lattice-type 3D-printed implants. CONCLUSIONS: Within the limits of this preclinical study, 3D-printed implants of double-rooted teeth showed high primary stability. However, 3D-printed implants with interlocking structures such as lattices might provide high secondary stability and successful osseointegration.

Effects of hyaluronic acid and deproteinized bovine bone mineral with 10% collagen for ridge preservation in compromised extraction sockets.

BACKGROUND: The aim of this study was to evaluate the efficacy of deproteinized bovine bone mineral with 10% collagen (DBBM-C) soaked with hyaluronic acid (HA) for ridge preservation in compromised extraction sockets. METHODS: Bilateral third, fourth premolars and first molar were hemisected, distal roots were extracted, and then combined endodontic periodontal lesion was induced in the remaining mesial roots. After 4 months, the mesial roots were extracted and the following four treatments were randomly performed: Absorbable collagen sponge (ACS), ACS soaked with HA (ACS+HA), ridge preservation with DBBM-C covered with a collagen membrane (RP), ridge preservation with DBBM-C mixed with HA and covered with a collagen membrane (RP+HA). Animals were sacrificed at 1 and 3 months following treatment. Ridge dimensional changes and bone formation were examined using microcomputed tomography, histology, and histomorphometry. RESULTS: At 1 month, ridge width was significantly higher in the RP and RP+HA groups than in the ACS and ACS+HA groups, while the highest proportion of mineralized bone was observed in ACS+HA group. At 3 months, ridge width remained significantly higher in the RP and RP+HA groups than in the ACS and ACS+HA groups. ACS+HA and RP+HA treatments featured the highest proportion of mineralized bone and bone volume density compared with the other groups. No statistical difference was observed between ACS+HA and RP+HA treatments. CONCLUSIONS: Ridge preservation with the mixture DBBM-C/HA prevented dimensional shrinkage and improved bone formation in compromised extraction sockets at 1 and 3 months.

Diagnostic Models for Screening of Periodontitis with Inflammatory Mediators and Microbial Profiles in Saliva.

This study aims to investigate and assess salivary biomarkers and microbial profiles as a means of diagnosing periodontitis. A total of 121 subjects were included: 28 periodontally healthy subjects, 24 with Stage I periodontitis, 24 with Stage II, 23 with Stage III, and 22 with Stage IV. Salivary proteins (including active matrix metalloproteinase-8 (MMP-8), pro-MMP-8, total MMP-8, C-reactive protein, secretory immunoglobulin A) and planktonic bacteria (including Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Fusobacterium nucleatum, Prevotella intermedia, Porphyromonas nigrescens, Parvimonas micra, Campylobacter rectus, Eubacterium nodatum, Eikenella corrodens, Streptococcus mutans, Staphylococcus aureus, Enterococcus faecalis, and Actinomyces viscosus) were measured from salivary samples. The performance of the diagnostic models was assessed by receiver operating characteristics (ROCs) and area under the ROC curve (AUC) analysis. The diagnostic models were constructed based on the subjects' proteins and/or microbial profiles, resulting in two potential diagnosis models that achieved better diagnostic powers, with an AUC value > 0.750 for the diagnosis of Stages II, III, and IV periodontitis (Model PA-I; AUC: 0.796, sensitivity: 0.754, specificity: 0.712) and for the diagnosis of Stages III and IV periodontitis (Model PA-II; AUC: 0.796, sensitivity: 0.756, specificity: 0.868). This study can contribute to screening for periodontitis based on salivary biomarkers.

Empirical design of slot-die having shallow reservoir for thin-film printed electronics.

Slot-die coating plays an important role in printed electronics, which are fabricated by stacking thin films and patterns. As electronic devices are being required to have higher performance, the importance of coating uniformity cannot be overestimated in the slot-die coating. The coating uniformity consists of two directions: nozzle direction, which is affected by the interior design of the head, and machine direction, which is majorly related to exterior operating conditions. In this research, the empirical design procedure of a slot-die head is proposed. The internal resistance values of the slot-die were calculated using the experimental parameter obtained through a coating experiment, and the acquired resistances were reflected in the modeling of the interior design of the slot-die head. The hanger type reservoir was adapted to minimize the consumption of ink. After fabricating the slot-die head, coating experiments were carried out using PEDOT:PSS ink. The resulting deviation of the coating thickness was within ±1.7%, thus proving that the proposed design predicted the uniformity of the actual thickness of the coating correctly. The significance of the slot-die design method presented in this paper is that it is based on the experimental equation that can be readily applied to the printed electronics industry.

The effect of anti-TNF treatment on osteoblastogenesis in ankylosing spondylitis: the number of circulating osteoblast-lineage cells in peripheral blood decreased after infliximab therapy in patients with ankylosing spondylitis.

OBJECTIVES: The full effect of anti-TNF therapy on new bone formation is still in debate in spondylitis fields. We sought to obtain circulating osteoblast-lineage cells in peripheral blood from ankylosing spondylitis (AS) patients and healthy control subjects, and to evaluate the effect of before and after anti TNF-α therapy on osteoblastogenesis in patients with AS. METHODS: Sixteen male patients with AS slated for infliximab therapy and 19 controls were recruited. We cultured osteoblast-lineage cells from peripheral blood and measured the optical density of their Alizarin red S staining. We also measured serum P1NP (procollagen type 1 N-terminal propeptide) as an early osteoblast differentiation marker, osteocalcin as a late osteoblast differentiation marker, and inflammatory markers. RESULTS: There were significantly more circulating osteoblast-lineage cells in patients than in controls. The number of circulating osteoblast-lineage cells and optical density of Alizarin red S staining decreased 14 weeks after infliximab therapy (p=0.028); serum level of P1NP decreased, but that of osteocalcin increased (p=0.002 and 0.007, respectively). CONCLUSIONS: Our data reveals that first, the circulating osteoblast-lineage cells are recoverable and increased in AS patients, and also that they decrease after infliximab therapy; second, infliximab therapy resolves early inflammation, but allows mature osteoblast differentiation in late inflammation. The culture of osteoblast-lineage cells in peripheral blood may be a candidate for a new modality with which to study spondylitis and other autoimmune diseases.

Sensitization of cardiac Ca²âº release sites by protein kinase C signaling: evidence from action of murrayafoline A.

In the present study, we explored the effects of a plant alkaloid compound, 1-methoxy-3-methylcarbazole (murrayafoline A, Mu-A), on focal and global Ca(2+) signaling, and the underlying cellular mechanisms. Rapid two-dimensional confocal Ca(2+) imaging and image analysis were used to measure Ca(2+) signals in rat ventricular myocytes. Application of Mu-A (10-100 µM) significantly enhanced the magnitude and rate of Ca(2+) release on depolarization with no change in Ca(2+) transient decay. Focal Ca(2+) release events (Ca(2+) sparks) occurred more often, and their duration and size were greater after the application of Mu-A. In addition, sarcoplasmic reticulum (SR) Ca(2+) loading and fractional release were increased by exposure to Mu-A. All these effects reached steady state within 2-3 min after Mu-A application. The higher occurrence of Ca(2+) sparks in the presence of Mu-A was resistant to SR Ca(2+) clamping, removal of extracellular Ca(2+) and Na(+), and blockade of either protein kinase A, Ca(2+)/calmodulin-dependent protein kinase II, phospholipase C, or inositol 1,4,5-trisphosphate receptors, but it was abolished by the inhibition of protein kinase C (PKC). SR Ca(2+) clamping prevented the Mu-A-induced Ca(2+) spark prolongation and enlargement. The Mu-A-induced enhancement of Ca(2+) transients was also eliminated by PKC blockade. Mu-A enhanced PKC activity in vitro. These results suggest that Mu-A may increase spark occurrence via its direct enhancement of PKC activity and subsequent sensitization of ryanodine receptor clusters and that this mechanism, as well as increased SR Ca(2+) loading, may partly explain larger and more rapid global Ca(2+) releases in the presence of Mu-A during depolarization.

Early effects of tumor necrosis factor inhibition on bone homeostasis after soluble tumor necrosis factor receptor use.

BACKGROUND/AIMS: Our aim was to assess whether short-term treatment with soluble tumor necrosis factor (TNF) receptor affects circulating markers of bone metabolism in rheumatoid arthritis (RA) patients. METHODS: Thirty-three active RA patients, treated with oral disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids for > 6 months, were administered etanercept for 12 weeks. Serum levels of bone metabolism markers were compared among patients treated with DMARDs at baseline and after etanercept treatment, normal controls and naive RA patients not previously treated with DMARDs (both age- and gender-matched). RESULTS: Bone-specific alkaline phosphatase (BSALP) and serum c-telopeptide (CTX)-1 levels were lower in RA patients treated with DMARDs than in DMARD-naive RA patients. After 12 weeks of etanercept treatment, serum CTX-1 and sclerostin levels increased. In patients whose DAS28 improved, the sclerostin level increased from 1.67 ± 2.12 pg/mL at baseline to 2.51 ± 3.03 pg/mL, which was statistically significant (p = 0.021). Increases in sclerostin levels after etanercept treatment were positively correlated with those of serum CTX-1 (r = 0.775), as were those of BSALP (r = 0.755). CONCLUSIONS: RA patients treated with DMARDs showed depressed bone metabolism compared to naive RA patients. Increases in serum CTX-1 and sclerostin levels after short-term etanercept treatment suggest reconstitution of bone metabolism homeostasis.

Effect of fibromyalgia syndrome on the health-related quality of life and economic burden in Korea.

OBJECTIVE: To investigate the health-related quality of life (HRQOL) and economic burden of patients with FM syndrome (FMS) and compare the changes in these parameters 3 months before and after FMS diagnosis. METHODS: A total of 2098 patients with FMS (1818 previously diagnosed with FMS and 280 newly diagnosed with FMS) were enrolled in this study. The newly diagnosed patients with FMS participated in a 3-month prospective observational study to assess HRQOL and economic burden in terms of direct health-care costs, direct non-health-care costs and indirect costs. HRQOL was estimated using the Short Form 36 Health Survey. RESULTS: Mean (S.D.) scores obtained on the physical component summary (PCS) and mental component summary (MCS) scales by patients with FMS were 34.01 (7.28) and 37.29 (11.17), respectively. The total expenditure for the 3 months before enrolment was $1481 (S.D. $2206). Indirect costs [$1126 (S.D. $2016)] were about three times higher than direct costs [$355 (S.D. $534)]. The PCS and MCS scores increased to 4.03 (S.D. 6.79) and 4.06 (S.D. 10.57), respectively, 3 months after the initial FMS diagnosis (P < 0.001, both). Total expenditure after FMS diagnosis was reduced by $1025 (S.D. $1347) as compared with costs before FMS diagnosis (P < 0.001). Conclusion. Patients with FMS experience a decline in their HRQOL and constitute a significant economic burden on health-service utilization. The improvement in health-related costs and HRQOL after a diagnosis of FMS demonstrates a need for early diagnosis and treatment of FMS to reduce costs and enhance HRQOL.

Influence of extraction method on quality and functionality of broccoli juice.

This study was performed to compare the quality and functionality of broccoli juice as affected by extraction method. Broccoli juice was extracted using method I (NUC Kuvings silent juicer), method II (NUC centrifugal juicer), and method III (NUC mixer), and the quality properties of the broccoli juices were analyzed using three different methods. Additionally, the antioxidative, anticancer, and anti-hyperglycemic activities of broccoli juice prepared by the three different methods were investigated in vitro. The broccoli juice made by method I contained the highest polyphenol and flavonoid contents at 1,226.24 mg/L and 1,018.32 mg/L, respectively. Particularly, broccoli juice prepared by method I showed higher DPPH and ABTS radical scavenging activities than those of the other samples. Additionally, broccoli juice made by method I showed the highest growth inhibitory effects against HeLa, A549, AGS, and HT-29 cancer cells. Broccoli juice prepared by method I had the highest α-glucosidase inhibitory effects. These results indicate that there are important differences in chemical and functional qualities between juice extraction techniques.

Reactivation of Silenced WT1 Transgene by Hypomethylating Agents - Implications for in vitro Modeling of Chemoimmunotherapy.

BACKGROUND: A cell line with transfected Wilms' tumor protein 1 (WT1) is has been used for the preclinical evaluation of novel treatment strategies of WT1 immunotherapy for leukemia due to the lack of appropriate murine leukemia cell line with endogenous WT1. However, silencing of the transgene occurs. Regarding the effects of hypomethylating agents (HMAs) on reactivation of silenced genes, HMAs are considered to be immune enhancers. METHODS: We treated murine WT1- transfected C1498 (mWT1-C1498) with increasing doses of decitabine (DAC) and azacitidine (AZA) to analyze their effects on transgene reactivation. RESULTS: DAC and AZA decreased the number of viable cells in a dose- or time-dependent manner. Quantification of WT1 mRNA level was analyzed by real-time polymerase chain reaction after mWT1-C1498 treated with increasing dose of HMA. DAC treatment for 48 h induced 1.4-, 14.6-, and 15.5-fold increment of WT1 mRNA level, compared to untreated sample, at 0.1, 1, and 10µM, respectively. Further increment of WT1 expression in the presence of 1 and 10µM DAC was evident at 72 h. AZA treatment also induced up-regulation of mRNA, but not to the same degree as with DAC treatment. The correlation between the incremental increases in WT1 mRNA by DAC was confirmed by Western blot and concomitant down-regulation of WT1 promoter methylation was revealed. CONCLUSION: The in vitro data show that HMA can induce reactivation of WT1 transgene and that DAC is more effective, at least in mWT1-C1498 cells, which suggests that the combination of DAC and mWT1-C1498 can be used for the development of the experimental model of HMA-combined WT1 immunotherapy targeting leukemia.

Proliferation and osteoblastic differentiation of bone marrow stem cells: comparison of vertebral body and iliac crest.

Bone marrow stem cells (BMSCs) can be obtained from the vertebral body (VB) and iliac crest (IC) for augmenting spinal arthrodesis. However, it is still not evaluated, which of the two sites would have a better BMSCs potential on Proliferation and osteoblastic differentiation is still not evaluated. Fourteen patients (10 men and 4 women) undergoing posterolateral lumbar arthrodesis and pedicle screw instrumentation were involved. The mean age was 54.7 years (range 31-75 years). Bone marrow aspirates were obtained from the vertebral body through the bilateral pedicle and were quantified relative to matched, bilateral aspirates from the iliac crest that were obtained from the same patient and at the same time. The mononuclear cell count and concentration of BMSCs were calculated and compared. Proliferation and osteoblastic differentiation of each of the BMSCs were characterized using biochemical and molecular biology techniques. Concentration (cells/mL) of BMSCs from VB and IC were 3.73 × 10(3) and 3.19 × 10(3), respectively (P > 0.05). VB and IC exhibited similar proliferation pattern at 3, 5 and 7 days, but BMSCs from the VB exhibited an increased mineralization staining with Alizarin Red S at 14 days. BMSCs from both anatomic sites expressed comparable levels of CD29, CD34, CD44, CD90 and CD105. VB and IC displayed similar levels of expression of ALP, type I collagen and osterix, but VB expressed higher level of osteocalcin and Runx-2, especially at 14 and 21 days. Our studies show that BMSCs from VB have osteogenic differentiation potential similar to IC. Based on these findings, we suggest that BMSCs from VB would be comparable candidates for osseous graft supplementation especially in spinal fusion procedures.

Surface reaction of sulfur-containing amino acids on Cu(110).

Adsorption behaviors of sulfur-containing amino acids, cysteine, methionine, and cystine molecules on Cu(110) surface were studied by core level photoelectron spectroscopy using synchrotron radiation. We found the following through the systematic comparisons of core level peaks such as S 2p, N 1s, and O 1s from different amino acids. At low coverage regimes, all the molecules form two distinct thiolate species, and their S 2p binding energy difference was about 0.9 eV. The relative populations of the two thiolates were different for different molecules and their coverage, which is due to the different bond strength of the sulfur-containing functional groups. At high coverage regimes, only cysteine molecules form zwitterionic state, which is related to the molecular ordering on Cu(110) surface.

Genetic polymorphisms of hypoxia-inducible factor-1 alpha and cardiovascular disease in hemodialysis patients.

BACKGROUND: Hemodialysis patients are prone to ischemic events potentially aggravated by hypoxia. The key player in adaptation to hypoxia is hypoxia-inducible factor-1 alpha (HIF-1alpha). Therefore, we investigated the association of HIF-1alpha polymorphisms with ischemia/hypoxia-related events in hemodialysis patients. METHODS: Patients on maintenance hemodialysis were enrolled from 4 training hospitals in Korea. Seven single nucleotide polymorphisms (SNP) of HIF-1alpha were genotyped. The association of these SNP with hypoxia-related clinical outcomes (ischemic diseases and anemia) and cancer was analyzed. RESULTS: A total of 376 patients participated in the study. No significant difference in genotype distribution was found between subjects with and without the hypoxia-related events. Three sets of linkage disequilibrium blocks were made for haplotype analyses (rs2783778 and rs7148720 in 5' upstream region; rs7143164 and rs10873142; rs2301113, rs11549465 and rs2057482). Of these, the CT haplotype in the first set was associated with both acute myocardial infarction and frequent intradialytic hypotension (acute myocardial infarction: adjusted odds ratio = 0.15, 95% CI: 0.03-0.69; frequent intradialytic hypotension: adjusted odds ratio = 0.29, 95% CI: 0.12-0.72). CONCLUSION: Genetic polymorphisms of HIF-1alpha were associated with acute myocardial infarction and intradialytic hypotension in hemodialysis patients.

The role of nuclear factor kappa B in lens epithelial cell proliferation using a capsular bag model.

PURPOSE: This study was performed to elucidate the role of nuclear factor kappaB (NF-kappaB) in lens epithelial cell proliferation in the capsular bag model for this study. METHODS: Capsular bags were prepared from porcine eyes and cultured in a 5% CO(2) atmosphere at 37 degrees C. NF-kappaB translocation was confirmed by immunohistochemistry and Western blot analysis. The effects of sulfasalazine and SN50 peptide, inhibitors of NF-kappaB activation, were observed by light microscopy and scanning electron microscopy. RESULTS: NF-kappaB was found in the cytoplasm of nonproliferated lens epithelial cells. However, NF-kappaB moved to the nucleus in proliferation cells, proliferating-cell-nuclear-antigen-positive cells. This translocation was inhibited by treatment with sulfasalazine or NF-kappaB SN50 peptide. These inhibitors also blocked lens epithelial cell migration from the equatorial to the posterior capsule. CONCLUSION: NF-kappaB controls proliferation and regulates the growth of lens epithelial cells. In this study, sulfasalazine and NF-kappaB SN50 peptide inhibited cell proliferation in the capsular bag model. These results suggest that the regulation of NF-kappaB in lens epithelial cells may modulate posterior capsule opacification.

Naturally occurring biflavonoid, ochnaflavone, inhibits cyclooxygenases-2 and 5-lipoxygenase in mouse bone marrow-derived mast cells.

Ochnaflavone is a medicinal herbal product isolated from Lonicera japonica that inhibits cyclooxygenase-2 (COX-2) dependent phases of prostaglandin D2 (PGD2) generation in bone marrow-derived mast cells (BMMC) in a concentration-dependent manner with IC50 values of 0.6 microM. Western blotting probed with specific anti-COX-2 antibodies showed that the decrease in quantity of the PGD2 product was accompanied by a decrease in the COX-2 protein level. In addition, this compound consistently inhibited the production of leukotriene C4 (LTC4) in a dose dependent manner, with an IC50 value of 6.56 microM. These results demonstrate that ochnaflavone has a dual cyclooxygenase-2/5-lipoxygenase inhibitory activity. Furthermore, this compound strongly inhibited degranulation reaction in a dose dependent manner, with an IC50 value of 3.01 microM. Therefore, this compound might provide a basis for novel anti-inflammatory drugs.

The naturally occurring biflavonoid, ochnaflavone, inhibits LPS-induced iNOS expression, which is mediated by ERK1/2 via NF-kappaB regulation, in RAW264.7 cells.

Ochnaflavone (OC), a naturally occurring biflavonoid with anti-inflammatory activity [S.J. Lee, J.H. Choi, H.W. Chang, S.S. Kang, H.P. Kim. Life Sci. 57(6), 1995, 551-558], was isolated from Lonicera japonica and its effects on inducible nitric oxide synthase (iNOS) gene expression was examined in RAW264.7 cells. U0126, an inhibitor of the extracellular signal-regulated kinase (ERK), significantly down-regulated lipopolysaccharide (LPS)-induced iNOS expression and promoter activity. Transactivation of LPS-stimulated NF-kappaB was inhibited by U0126. These results suggest that the transcription factor NF-kappaB is involved in ERK-mediated iNOS regulation and that activation of the Ras/ERK pathway contributes to the induction of iNOS expression in RAW264.7 cells in response to LPS. OC treatment inhibited the production of nitric oxide in a concentration-dependent manner and also blocked the LPS-induced expression of iNOS. These inhibitory effects were associated with reduced ERK1/2 activity. OC inhibited the phosphorylation of c-Jun NH2-terminal kinase (JNK) and p38 mitogen-activated protein kinase. The findings herein show that the inhibition of LPS-induced ERK1/2 activation may be a contributing factor to the main mechanisms by which OC inhibits RAW264.7. To clarify the mechanistic basis for its ability to inhibit iNOS induction, we examined the effect of OC on the transactivation of the iNOS gene by luciferase reporter activity using the -1588 flanking region. OC potently suppressed reporter gene activity. We also report here, for the first time, that LPS-induced iNOS expression was abolished by OC in RAW264.7 cells through by blocking the inhibition of transcription factor NF-kappaB binding activities. These activities are associated with the down-regulation of inhibitor kappaB (IkappaB) kinase (IKK) activity by OC (6 microM), thus inhibiting LPS-induced phosphorylation as well as the degradation of IkappaBalpha. These findings suggest that the inhibition of LPS-induced NO formation by OC is due to its inhibition of NF-kappaB, which may be the mechanistic basis for the anti-inflammatory effects of OC.

Ginkgetin, a Biflavone from Ginko biloba leaves, inhibits cyclooxygenases-2 and 5-lipoxygenase in mouse bone marrow-derived mast cells.

Ginkgetin, a biflavone from Ginkgo biloba leaves, was previously reported to be a phospholipase A(2) inhibitor and this compound showed the potent antiarthritic activity in rat adjuvant-induced arthritis as well as analgesic activity. This investigation was carried out to find effects on cyclooxygenase-2 (COX-2) in vitro effect. Ginkgetin inhibits COX-2 dependent phases of prostaglandin D(2) (PGD(2)) generation in bone marrow-derived mast cells (BMMC) in a concentration-dependent manner with IC(50) values of 0.75 microM. Western blotting probed with specific anti-COX-2 antibodies showed that the decrease in quantity of the PGD(2) product was accompanied by a decrease in the COX-2 protein level. In addition, this compound consistently inhibited the production of leukotriene C(4) (LTC(4)) in a dose dependent manner, with an IC(50) value of 0.33 microM. These results demonstrate that ginkgetin has a dual cyclooxygenase-2/5-lipoxygenase inhibitory activity. Furthermore, this compound also inhibited degranulation reaction in a dose dependent manner, with an IC(50) value of 6.52 microM. Therefore, this compound might provide a basis for novel anti-inflammatory agents.

Inhibition of prostaglandin production by a structurally-optimized flavonoid derivative, 2',4',7-trimethoxyflavone and cellular action mechanism.

Flavonoids possess anti-inflammatory activity in vitro and in vivo. In order to find the anti-inflammatory flavone derivatives having optimum chemical structures, various flavones were previously synthesized and evaluated for their inhibitory activity of prostaglandin E(2) (PGE(2)) production from lipopolysaccharide (LPS)-treated mouse macrophage cell line, RAW 264.7 cells. Through this screening procedure, 2',4',7-trimethoxyflavone (TMF) was selected for further pharmacological study. From the present investigation, it was found that TMF potently inhibited PGE(2) production from LPS-treated RAW cells with an IC(50) of 0.48 microM, compared to the IC(50) values of 0.07 and 1.09 microM for NS-398 and wogonin. TMF, however, did not inhibit cyclooxygenase-2 (COX-2) activity or COX-2 expression level. Instead, TMF was proved to be a phospholipase A(2) (PLA(2)) inhibitor. The IC(50) values of TMF against secretory PLA(2)-IIA (sPLA(2)-IIA) and cytosolic PLA(2) (cPLA(2)) were 70.5 and 70.4 microM, respectively. At doses of 10-250 microg/ear, TMF also showed in vivo anti-inflammatory activity by topical application against mouse croton oil-induced ear edema assay, suggesting a potential for new anti-inflammatory agent.

Dual inhibition of cyclooxygenases-2 and 5-lipoxygenase by deoxypodophyllotoxin in mouse bone marrow-derived mast cells.

Deoxypodophyllotoxin (Anthricin) is a medicinal herbal product isolated from Anthriscus sylvestris HOFFM. that inhibits cyclooxygenase-2 (COX-2) and COX-1-dependent phases of prostaglandin D(2) (PGD(2)) generation in bone marrow-derived mast cells (BMMC) in a concentration-dependent manner with IC(50) values of 1.89 microM and 65.3 microM, respectively. This study also found that this compound inhibited COX-1 and 2-dependent conversion of the exogenous arachidonic acid to PGD(2) in a dose-dependent manner with an IC(50) values of 0.01 microM and 12.1 microM, respectively using a COX enzyme assay kit. However, this compound did not inhibit COX-2 protein expression up to a concentration of 30 microM in the BMMC, indicating that deoxypodophyllotoxin directly inhibits COX-2 activity. Furthermore, this compound consistently inhibited the production of leukotriene C(4) (LTC(4)) in a dose dependent manner, with an IC(50) value of 0.37 microM. These results demonstrate that deoxypodophyllotoxin has a dual cyclooxygenase-2 selective/5-lipoxygenase inhibitory activity, and therefore this compound might provide a basis for novel anti-inflammatory drugs.

Deoxypodophyllotoxin, a naturally occurring lignan, inhibits the passive cutaneous anaphylaxis reaction.

This study examined the effect of a podophyllotoxin derivative, deoxypodophyllotoxin (anthricin), which is a medicinal herb product isolated from Anthriscus sylvestris Hoffm. Deoxypodophyllotoxin was tested in a rat PCA (passive cutaneous anaphylaxis) assay by administering deoxypodophyllotoxin intraperitoneally (1.0 to 10 mg/kg, i.p.) and intravenously (0.25 to 1.0 mg/kg, i.v.). Deoxypodophyllotoxin dose-dependently inhibited the PCA reaction activated by anti-dinitrophenyl (DNP) IgE. The PCA inhibitory activity of deoxypodophyllotoxin was stronger than those of prednisolone and indomethacin, which were used as positive controls. These results suggest that deoxypodophyllotoxin may be beneficial in regulating the immediate-type allergic reaction.