Radioisotope identification using an energy-weighted algorithm with a proof-of-principle radiation portal monitor based on plastic scintillators.

In this study, we validated the feasibility of an energy weighted algorithm that highlights a characteristic area including the Compton edge as a single peak in a proof-of-principle radiation portal monitor system with a plastic scintillator measuring 50 × 100 × 5 cm3. We measured the energy weighted spectra with steel shielding and the dynamic movements of the 137Cs and 60Co sources. The results showed that the peak locations of each source could be identified under shielded or dynamic motion conditions, each within a maximum difference of 0.08 MeV.

Scopoletin downregulates MMP­1 expression in human fibroblasts via inhibition of p38 phosphorylation.

Irradiation of keratinocytes by ultraviolet B induces cytokine production, which in turn activates fibroblasts to produce cytokines and increase matrix metallopeptidase (MMP)­1 protein expression. The present study investigated the effect and potential mechanisms of scopoletin on the regulation of MMP­1 expression in fibroblasts. Scopoletin was isolated from Artemisia capillaris crude extract. Treatment of fibroblasts with scopoletin resulted in a decrease in the protein expression of MMP­1 following stimulation with human keratinocyte (HaCaT) conditioned medium. To further explore the mechanism underlying this effect, the expression levels of proteins in the mitogen­activated protein kinase (MAPK) and nuclear factor­κB (NF­κB) signaling pathways were evaluated via western blot analysis. The mRNA expression levels of interleukin (IL)­1α and tumor necrosis factor (TNF) α were evaluated via reverse transcription­quantitative polymerase chain reaction. The effect of scopoletin on cell viability was assessed with the MTT assay. The results demonstrated that scopoletin treatment markedly decreased MMP­1, IL­1α and TNFα mRNA expression in fibroblasts stimulated with HaCaT conditioned medium (40 mJ/cm2), without any apparent cell cytotoxicity, and in a dose­dependent manner. In addition, western blot analysis demonstrated that scopoletin reduced the phosphorylation of p38 MAPK in fibroblasts. In summary, the present study demonstrated that scopoletin inhibited MMP­1 and proinflammatory cytokine expression by inhibiting p38 MAPK phosphorylation. These findings suggest that scopoletin may have potential as a therapeutic agent to prevent and treat photoaging of the skin.

Soyasaponin Ag inhibits α­MSH­induced melanogenesis in B16F10 melanoma cells via the downregulation of TRP­2.

Saponins, which are glycosylated, represent a diverse group of biologically functional products in plants. In the present study, we investigated the effects of soyasaponin Ag, a secondary metabolite extracted from soybean, on α­melanocyte-stimulating hormone (α­MSH)­induced melanin synthesis in B16F10 mouse melanoma cells and the underlying molecular mechanisms. To elucidate the mechanisms through which soyasaponin Ag inhibits melanin synthesis, we performed cellular tyrosinase activity assays and analyzed the expression of the melanogenesis­related genes, tyrosinase, tyrosinase­related protein (TRP)­1 and TRP­2. We demonstrated that soyasaponin Ag inhibited α­MSH­induced melanin synthesis in melanoma cells. Of note, soyasaponin Ag had no inhibitory effect on intracellular tyrosinase activity. However, soyasaponin Ag inhibited TRP­2 expression in a dose­dependent manner. Therefore, the depigmenting effect of soyasaponin Ag may be due to the inhibition of tyrosinase expression or the enhancement of tyrosinase degradation. Moreover, soyasaponin Ag did not exert any toxic on B16F10 mouse melanoma cells, suggesting that soyasaponin is a safe component for use in skin care cosmetic formulations that are used for skin whitening.

Protective effects of a polymethoxy flavonoids-rich Citrus aurantium peel extract on liver fibrosis induced by bile duct ligation in mice.

OBJECTIVE: To evaluate the possible protective effect of Citrus aurantium peel extract (CAE) against apoptosis in cholestatic liver fibrosis induced by bile duct ligation in mice. METHODS: Male ICR mice were divided to 5 groups: 1) Control group (Sham-operated mice), 2) Cholestatic liver injury group induced by bile duct ligation (BDL), 3) BDL mice treated with silymarin (200 mg/kg) for 4 weeks, 4) BDL mice treated with 50 mg/kg CAE for 4 weeks, 5) BDL mice treated with 200 mg/kg CAE for 4 weeks. Mice were sacrificed and liver fibrosis was evaluated by serum and hepatic tissue biochemistry tests and liver histopathological examination. Effects of CAE on inflammation and apoptosis gene regulation were investigated through real-time PCR. CAE effect on lipid metabolism related signaling was determined by western blot analysis. RESULTS: In BDL mice, administration of CAE for 4 weeks markedly attenuated liver fibrosis based on histopathological alteration. Serum and hepatic tissue biochemistry results revealed that CAE (50 and 200 mg/kg) decreased the levels of alanine transaminase, aspartate transaminase, gamma-glutamyl transferase, total bilirubin, nitric oxide, and thiobarbituric acid reactive substances. Real-time PCR and western blot analysis showed that CAE regulated inflammation, apoptosis, and lipid metabolism factors increased by BDL. Interleukin family, tumor necrosis factor α, and related apoptosis factors mRNA levels were increased by BDL treatment. However, these increases were suppressed by CAE administration. In addition, CAE effectively increased phosphorylation of AMP-activated protein kinase, nuclear factor E2-related factor 2, and related cytoprotective proteins. CONCLUSIONS: CAE can efficiently regulate BDL-induced liver injury with antioxidant, anti-inflammatory, and anti-apoptotic activities.

Is a Price Increase Policy Enough for Adolescent Smokers?: Factors Affecting the Effectiveness of Increasing Cigarette Prices Among Korean Adolescent Smokers.

BACKGROUND: Cigarette pricing policy is one tool for controlling smoking behavior on a national scale. It is unclear, however, what effects such policy has on adolescents and which characteristic subgroups of adolescents are more or less sensitive to cigarette pricing policy. MATERIALS AND METHODS: Our data came from the 2013 Korea Youth Risk Behavior Web-based Survey. The dependent variable was whether or not a participant was classified as a "persistent smokers," defined as a smoker who would continue smoking despite any price increase. Other variables of interest were smoking days (quantity), previous attempts to stop smoking, and previous education on smoking cessation. The statistical analysis was performed using weighted data and the SURVEYFREQ and SURVEYLOGISTIC procedures in SAS 9.3. RESULTS: Among 7094 adolescent smokers (5349 males and 1745 females), 19.9% of males and 25.1% of females reported as persistent smokers. Compared with light smokers, heavy smokers are more likely to be persistent smokers (male: odds ratio [OR] = 2.45, 95% confidence interval [CI] = 2.04-2.95, P value < .001; female: OR = 3.23, 95% CI = 2.44-4.27, P value < .001). When we stratified the data by household income, previous attempts to stop smoking, and previous education on smoking cessation, that trend remained statistically significant. CONCLUSIONS: Because heavier smokers with higher risk of health-related consequences were less sensitive to pricing policy than mild smokers, pricing policy alone is not enough to reduce the societal burden caused by smoking. We suggest that additional cessation policy is needed along with pricing policy for adolescents with heavier smoking behavior in Korea. IMPLICATION: This study shows that heavy smokers are more likely to be persistent smokers despite the cigarette price increase policy, compared with light smokers in Korean adolescents. Because heavier smokers were less sensitive to pricing policy than mild smokers, pricing policy alone is not enough to reduce the societal burden caused by smoking. We suggest that additional tobacco control policies should be evaluated and effective ones implemented in addition to cigarette prices to reduce smoking among regular adolescent smokers.

Validation of energy-weighted algorithm for radiation portal monitor using plastic scintillator.

To prevent illicit tracking of radionuclides, radiation portal monitor (RPM) systems employing plastic scintillators have been used in ports and airports. However, their poor energy resolution makes the discrimination of radioactive material inaccurate. In this study, an energy weight algorithm was validated to determine (133)Ba, (22)Na, (137)Cs, and (60)Co by using a plastic scintillator. The Compton edges of energy spectra were converted to peaks based on the algorithm. The peaks have a maximum error of 6% towards the theoretical Compton edge.

Creating Anti-icing Surfaces via the Direct Immobilization of Antifreeze Proteins on Aluminum.

Cryoprotectants such as antifreeze proteins (AFPs) and sugar molecules may provide a solution for icing problems. These anti-icing substances protect cells and tissues from freezing by inhibiting ice formation. In this study, we developed a method for coating an industrial metal material (aluminum, Al) with AFP from the Antarctic marine diatom, Chaetoceros neogracile (Cn-AFP), to prevent or delay ice formation. To coat Al with Cn-AFP, we used an Al-binding peptide (ABP) as a conjugator and fused it with Cn-AFP. The ABP bound well to the Al and did not considerably change the functional properties of AFP. Cn-AFP-coated Al (Cn-AFP-Al) showed a sufficiently low supercooling point. Additional trehalose coating of Cn-AFP-Al considerably delayed AFP denaturation on the Al without affecting its antifreeze activity. This metal surface-coating method using trehalose-fortified AFP can be applied to other metals important in the aircraft and cold storage fields where anti-icing materials are critical.

Different functions of MdtB and MdtC subunits in the heterotrimeric efflux transporter MdtB(2)C complex of Escherichia coli.

In contrast to homotrimeric transporters of the RND (resistance-nodulation-division) superfamily, which often conduct efflux transport of a wide range of substrates by the functionally rotating mechanism, the mechanism utilized by the heterotrimeric members of this family, which also perform multidrug efflux, is unclear. We examined one heterotrimeric transporter, the MdtB(2)C complex of Escherichia coli, by an extensive cysteine scanning mutagenesis of residues likely involved in ligand transport. Many such mutations in MdtC strongly decreased the level of cloxacillin transport, whereas mutations of corresponding residues in MdtB did not affect transport. Furthermore, many such residues in MdtC were covalently modified by fluorescein maleimide, which acted as a substrate and presumably produced labeling of the residues in the substrate path. In contrast, few residues in MdtB were labeled. Together with the previous data showing that the inactivation of proton translocation channel in MdtC has an only modest effect on transport yet in MdtB totally inactivated the activity, these results suggest that the two subunits, MdtB and MdtC, play very different roles, MdtC likely involved in substrate binding and transport and MdtB presumably inducing the conformational change needed for transport through proton translocation. Three-dimensional models of MdtB and MdtC, based on sequence homology with the AcrB transporter, also support this interpretation.

Experience of 100 laparoscopic radical prostatectomies performed by a single surgeon: an analysis of surgical and functional outcomes.

PURPOSE: We analyzed the surgical and functional outcomes of 100 consecutive laparo-scopic radical prostatectomies (LRP) performed by a single surgeon. MATERIALS AND METHODS: Between October 2007 and May 2010, a total of 100 consecutive patients underwent LRP for prostate cancer at our institution. We retrospectively reviewed the medical records of these patients to determine surgical and functional results. We compared surgical and functional outcomes between three groups divided on the basis of operation period (Group 1; first 40 cases; Group 2; next 30 cases; Group 3; last 30 cases). RESULTS: The operative time decreased significantly as the surgeon's experience increased over time (P<0.01). The learning curve for operative time was surpassed after approximately 40 cases. The overall positive surgical margin (PSM) rate was 17.5% in Group 1, 16.7% in Group 2, and 10% in Group 3. For organ-confined disease, the PSM rate was 2.5%, 6.7%, and 3.3% in Groups 1, 2, and 3, respectively. The continence rate (absence of a pad) was 73.2% and the social continence rate was 94.7% at 12 months after surgery. There was a significant difference in continence (absence of pad) between the early (Group 1) and late group (Group 3) at 1, 3, and 6 months (P<0.0001). The continence rate was not affected by whether the pubic bone-anchoring procedure or the Rocco suture method was used. The overall potency rate was 16.7% and 48.6% at 6 and 12 months, respectively. For bilateral nerve-sparing cases, the potency rate was 20% and 57.1% at 6 and 12 months, respectively. CONCLUSIONS: Our surgical and functional outcomes indicate that even in this 'robotic era', LRP is still an attractive treatment option for patients with localized prostate cancer, especially in areas with limited access to surgical robots.

Concentration of cytokines in the aqueous humor of patients with naive, recurrent and regressed CNV associated with amd after bevacizumab treatment.

PURPOSE: : To evaluate the concentration of various cytokines in the aqueous humor of patients with naive, recurrent, and regressed choroidal neovascularization (CNV) of age-related macular degeneration after bevacizumab treatment. METHODS: : Aqueous humor samples were collected from 36 eyes with age-related macular degeneration and 10 controls during cataract surgery. Of 36 patients with age-related macular degeneration, 5 eyes were naïve to bevacizumab injection, 14 eyes had recurrent CNV after bevacizumab treatment, and 17 eyes had regressed CNV after bevacizumab treatment. Cytokines were measured by an immunoassay using multianalyte biochip array technology (Evidence investigator cytokine and growth factor biochip array, RANDOX laboratories Ltd., Crumlin, UK). RESULTS: : No significant difference in the cytokine levels was noted between the control group and the naïve CNV group (all P > 0.05). Vascular endothelial growth factor in both naive (66.8 +/- 35.1 pg/mL) and recurrent CNV groups (55.7 +/- 63.0 pg/mL) was significantly higher compared with regressed CNV group (9.8 +/- 12.8 pg/mL, P = 0.025 and P = 0.004, respectively) but was not statistically different from the control group (81.8 +/- 43.7 pg/mL, P = 0.310 and P = 0.212, respectively). The aqueous humor level of tumor necrosis factor-alpha and interleukin (IL)-2 was significantly lower in recurrent CNV group (P = 0.036 and P = 0.019) compared with the control group. In the active CNV patients (recurrent and naïve CNV groups), the aqueous humor levels of IL-6 and IL-8 significantly correlated with the size of CNV (rho = 0.692, P = 0.001 and rho = 0.745, P < 0.001, respectively). CONCLUSION: : Levels of Vascular endothelial growth factor measured in the aqueous humor were significantly related to the disease activity of CNV in age-related macular degeneration. Moreover, IL-2, IL-6, IL-8, and tumor necrosis factor-alpha may be related to the activity of CNV.

Effect of intravitreal bevacizumab injection on aqueous humor cytokine levels in clinically significant macular edema.

PURPOSE: To determine the effect of intravitreal bevacizumab (Avastin, Genentech, Inc., San Francisco, CA) injection on aqueous humor cytokine levels in clinically significant macular edema (CSME). DESIGN: Retrospective, comparative study. PARTICIPANTS: Seventeen eyes undergoing intravitreal injection for CSME and 11 eyes undergoing cataract surgery as negative controls. Nine patients with CSME were naïve to intravitreal bevacizumab injection (CSME group 1), and 8 patients previously received 1 intravitreal bevacizumab injection at a mean of 9.6+/-1.4 weeks earlier (CSME group 2). METHODS: Aqueous humor samples were collected before performing intravitreal injection in the CSME group and during cataract surgery in the control group. Aqueous cytokine levels were determined by immunoassay using multianalyte biochip array technology. MAIN OUTCOME MEASURES: The concentration of cytokines in the aqueous humor was recorded as a mean (+/- standard deviation) in CSME groups 1 and 2 and the control group. Correlations of aqueous humor cytokine levels were evaluated. RESULTS: Significantly higher levels of interleukin (IL)-6, IL-8, and monocyte chemoattractant protein (MCP)-1 were noted in patients with CSME compared with controls. Although higher vascular endothelial growth factor (VEGF) levels were noted in CSME group 1 (P = 0.001), a lower level of VEGF was noted after intravitreal bevacizumab injection in CSME group 2 (P = 0.004) compared with the control group. VEGF levels were also lower in CSME group 2 compared with CSME group 1 (P = 0.001). In CSME group 2, a significant negative correlation was observed between VEGF and IL-6 (rho = -0.833, P = 0.01) and VEGF and MCP-1 (rho = -0.736, P = 0.037). CONCLUSIONS: Significantly higher levels of IL-6, IL-8, VEGF, and MCP-1 were noted in the aqueous humor of CSME. However, recurrence of macular edema was noted with significantly lower concentrations of VEGF after a single intravitreal injection of bevacizumab. This suggests the potential importance of IL-6 and MCP-1 in the pathogenesis of CSME. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Activation of extracellular signal regulated kinase 1/2 in human dermal microvascular endothelial cells stimulated by anti-endothelial cell antibodies in sera of patients with Behçet's disease.

Anti-endothelial cell antibodies (AECA) have been detected in the sera of patients with Behçet's disease (BD). The isotype of AECA from BD is IgM recognizing 44 kDa antigen (IgM-AECA) of human dermal microvascular endothelial cells (HDMEC). After stimulation of HDMEC with AECA-positive sera from BD patients, the expression of intercellular cell adhesion molecule-1 (ICAM-1) on HDMEC increases significantly. Mitogen-activated protein kinase (MAPK) cascade is one of protein kinase families activated by a wide spectrum of extracellular stimuli. There are several subtypes, including extracellular signal regulated kinase (ERK)1/2, c-Jun NH(2) terminal kinase (JNK), and p38 cascades, and they regulate various cellular processes such as cell growth, differentiation, and inflammation. We examined the involvement of MAPK as a signal transduction pathway in the IgM-AECA-induced ICAM-1 expression. We used enzyme-linked immunosorbent assay (ELISA) and fluorescence-activated cell sorting (FACS) for detecting the induction of ICAM-1 on HDMEC. We also examined the production of tumor necrosis factor alpha (TNFalpha) or interleukin-1alpha (IL-1alpha) by HDMEC after stimulation with IgM-AECA, and checked the involvement of MAPK by Western blot assay. IgM-AECA cocktail from 8 patients with BD induced expression of the ICAM-1 on HDMEC. Neither TNFalpha nor IL-1alpha was detected by ELISA, FACS or reverse transcriptase-polymerase chain reaction in activated HDMEC cultures. IgM-AECA cocktail activated ERK1/2 and showed peak activities at 5 min after the stimulation. Specific MAPK/ERK kinase inhibitor PD98059 inhibited IgM-AECA-induced ERK1/2 activities and ICAM-1 expression on HDMEC at a concentration of 60 microM. IgM-AECA can play a pathogenic role in induction of vasculitis and inflammatory lesions of BD by directly activating endothelial cells, not by production of TNFalpha or IL-1alpha from HDMEC. ERK1/2 are involved in expression of ICAM-1 on HDMEC stimulated with IgM-AECA.