Strain variation in Bacillus cereus biofilms and their susceptibility to extracellular matrix-degrading enzymes.

Bacillus cereus is a foodborne pathogen and can form biofilms on food contact surfaces, which causes food hygiene problems. While it is necessary to understand strain-dependent variation to effectively control these biofilms, strain-to-strain variation in the structure of B. cereus biofilms is poorly understood. In this study, B. cereus strains from tatsoi (BC4, BC10, and BC72) and the ATCC 10987 reference strain were incubated at 30°C to form biofilms in the presence of the extracellular matrix-degrading enzymes DNase I, proteinase K, dispase II, cellulase, amyloglucosidase, and α-amylase to assess the susceptibility to these enzymes. The four strains exhibited four different patterns in terms of biofilm susceptibility to the enzymes as well as morphology of surface-attached biofilms or suspended cell aggregates. DNase I inhibited the biofilm formation of strains ATCC 10987 and BC4 but not of strains BC10 and BC72. This result suggests that some strains may not have extracellular DNA, or their extracellular DNA may be protected in their biofilms. In addition, the strains exhibited different patterns of susceptibility to protein- and carbohydrate-degrading enzymes. While other strains were resistant, strains ATCC 10987 and BC4 were susceptible to cellulase, suggesting that cellulose or its similar polysaccharides may exist and play an essential role in their biofilm formation. Our compositional and imaging analyses of strains ATCC 10987 and BC4 suggested that the physicochemical properties of their biofilms are distinct, as calculated by the carbohydrate to protein ratio. Taken together, our study suggests that the extracellular matrix of B. cereus biofilms may be highly diverse and provides insight into the diverse mechanisms of biofilm formation among B. cereus strains.

Bioequivalence for a Fixed-Dose Combination Formulation of Bazedoxifene and Cholecalciferol Compared With the Corresponding Single Entities Given Together.

A fixed-dose combination (FDC) formulation of bazedoxifene 20 mg and cholecalciferol 8 mg was developed to increase medication compliance and convenience for osteoporosis patients. This study was conducted to demonstrate bioequivalence by comparing the pharmacokinetic (PK) profiles and tolerability of an FDC tablet and the individual component tablets. A randomized, open-label, single-dosing, 2-treatment, 2-period, 2-sequence crossover study was conducted in 52 healthy subjects. All subjects were randomly assigned to 2 sequences, and they received FDC tablets of bazedoxifene and cholecalciferol and individual component tablets. Serial blood samples for PK evaluation were collected up to 24 hours predose and 120 hours postdose, and the PK parameters were estimated by noncompartmental methods. Throughout the study, tolerability was assessed based on adverse events, vital signs, and clinical laboratory tests. Of the enrolled 52 subjects, 47 subjects completed the study. The results, the geometric mean ratios (GMRs) and 90% confidence intervals (90%CIs), of bazedoxifene Cmax and AUC0-t for FDC to single entities given together were 0.98 (0.91-1.05) and 1.02 (0.97-1.07), respectively. The GMRs (90%CIs) of cholecalciferol Cmax and AUC0-t for FDC to single entities given together were 0.96 (0.91-1.00) and 0.94 (0.90-0.99), respectively. Overall, the GMRs (90%CIs) of the PK parameter of bazedoxifene and cholecalciferol fell within the conventional bioequivalence range of 0.8-1.25. There were no clinically significant differences in the safety profile between the 2 treatments. In conclusion, this study confirmed the development of a new FDC drug by demonstrating that the FDC formulation of bazedoxifene and cholecalciferol is biologically equivalent to the coadministered individual formulations.

Comparison of pharmacokinetics and safety characteristics between two olopatadine hydrochloride 5 mg tablet formulations in healthy Korean subjects.

Histamine acts by binding to four histamine receptors (H1 to H4), of which the H1 is known to participate in dilate blood vessels, bronchoconstriction, and pruritus. Olopatadine hydrochloride blocks the release of histamine from mast cells and it inhibits H1 receptor activation. Olopatadine hydrochloride is anti-allergic agent that is effectively used. The object of this study had conducted to compare the pharmacokinetics (PKs) and safety characteristics between olopatadine hydrochloride 5 mg (test formulation) and olopatadine hydrochloride 5 mg (reference formulation; Alerac ®) in Korean subjects. This study had conducted an open-label, randomized, fasting condition, single-dose, 2-treatment, 2-period, 2-way crossover. Subjects received single-dosing of reference formulation or test formulation in each period and blood samples were collected over 24 hours after administration for PK analysis. A wash-out period of 7 days was placed between the doses. Plasma concentration of olopatadine were determined using liquid chromatography-tandem spectrometry mass (LC-MS/MS). A total of 32 subjects were enrolled and 28 subjects completed. There were not clinical significantly different in the safety between two treatment groups for 32 subjects who administered the study drug more than once. The geometric mean ratio of test formulation to reference formulation and its 90% confidence intervals for The peak plasma concentration (Cmax) and the areas under the plasma concentration-time curve from 0 to the last concentration (AUClast) were 1.0845 (1.0107-1.1637) and 1.0220 (1.0005-1.0439), respectively. Therefore, the test formulation was bioequivalent in PK characteristics and was equally safe as the reference formulation. TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0005943.

A randomized, open-label, crossover study to compare the safety and pharmacokinetics of two tablet formulations of tenofovir (tenofovir disoproxil and tenofovir disoproxil fumarate) in healthy subjects.

PURPOSE: This study was performed to compare the pharmacokinetic properties and assess bioequivalence for the test formulation (HUG116 tablet; tenofovir disoproxil) and reference formulation (Viread tablet; tenofovir disoproxil fumarate). MATERIALS AND METHODS: A randomized, open-label, single-dosing, two-treatment, two-period, two-sequence cross-over study was conducted in 50 healthy subjects. All subjects were randomly assigned to one of the two sequences, and they received a single dose of test or reference formulation in the first period and the alternative formulation during the next period under fasting conditions. Serial blood samples for pharmacokinetic evaluation were collected up to 72 hours post dose, and the pharmacokinetic parameters were estimated by noncompartmental methods. Throughout the study, tolerability was assessed based on adverse events, vital signs, and clinical laboratory tests. RESULTS: The test formulation showed similar pharmacokinetic profiles to those of the reference formulation. The geometric mean ratio and 90% confidence interval (CI) of the test formulation to the reference formulation for maximum plasma concentration (Cmax) was 0.93 (0.87 - 0.99), and the corresponding value for the area under the concentration-time curve from time zero to time of last quantifiable concentration (AUCt) was 0.94 (0.89 - 0.99). Both CIs were within the conventional bioequivalence range of 0.8 - 1.25. The tolerability profile was not significantly different between the test and reference formulations. CONCLUSION: This study found that the PKs of the test formulation (HUG116 tablet; tenofovir disoproxil) and reference formulation (Viread tablet; tenofovir disoproxil fumarate) were similar, and the test formulation met the regulatory criteria for assuming bioequivalence with the reference formulation.

Pharmacokinetic comparison of two bazedoxifene acetate 20 mg tablet formulations in healthy Korean male volunteers.

Bazedoxifene, used as bazedoxifene acetate, is a selective estrogen receptor modulator that selectively affects the uterus, breast tissue, bone metabolism, and lipid metabolism by antagonizing or enhancing estrogens in the estrogen receptor in the tissue. This study was conducted as an open, randomized, two-period, two-treatment, crossover design to compare the pharmacokinetic (PK) characteristics and tolerability of two bazedoxifene tablets when administered to 50 healthy Korean male volunteers. Enrolled subjects were randomly allocated to 2 sequences of a single oral administration of a test drug and a reference drug, or vice versa with a 14-day washout period between the two doses. Serial blood samples were collected over 96 h for PK analysis. Plasma concentration of bazedoxifene was assayed using liquid chromatography-tandem spectrometry mass. Forty-five participants completed the study with no clinically relevant safety issues. The peak concentrations (Cmax, mean ± strandard deviation) of reference drug and test drug were 3.191 ± 1.080 and 3.231 ± 1.346 ng/mL, respectively, and the areas under the plasma concentration-time curve from 0 to the last measurable concentration (AUClast) were 44.697 ± 21.168 ng∙h/mL and 45.902 ± 23.130 ng∙h/mL, respectively. The geometric mean ratios of test drug to reference drug and their 90% confidence intervals for Cmax and AUClast were 0.9913 (0.8828-1.1132) and 1.0106 (0.9345-1.0929), respectively. The incidence of adverse events between the two formulations was similar. The present study showed that PK and tolerability of two bazedoxifene tablet formulations were comparable when administered to healthy Korean male volunteers. TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0003978.

Multidrug Resistance, Biofilm Formation, and Virulence of Escherichia coli Isolates from Commercial Meat and Vegetable Products.

Escherichia coli is an important food safety and public health concern because of its pathogenicity and potential for antimicrobial resistance. E. coli isolates as food contaminants and their antimicrobial resistance, biofilm-forming ability, and virulence genes were analyzed to identify the potential of E. coli in food as a major transmission route for antimicrobial resistance and infectious agents. Among the 709 samples of minced meat and fresh vegetable products tested, 18.6% were positive for E. coli. One hundred nine (29.2%) out of 383 E. coli isolates were resistant to 1 or more of the 25 tested antimicrobials. Among the isolates from minced pork, the highest rate of resistance was observed for tetracycline (52.8%), followed by ampicillin (41.6%). The highest resistance rates against tetracycline were coincident with the high amount of tetracycline sold for veterinary use. Because penicillin is the most frequently used antimicrobial in humans, with 4.52 defined daily doses per 1000 people per day, the high rate of resistance to ampicillin (41.6%) supported the potential risk of E. coli food contaminants. However, only 1.3% of the isolates possessed the virulence genes commonly involved in foodborne outbreaks of E. coli. Sixty-seven isolates (17.5%) were multidrug-resistant (MDR), and the highest MDR was observed against 14 antimicrobials. Most of the MDR E. coli isolates showed biofilm-forming ability. Therefore, these isolates will have additional protection from environmental stresses, including antimicrobials. Given the importance of E. coli to food safety and public health, our results on the prevalence of antimicrobial resistance and virulence factors provide useful information for risk management options to protect public health.

The effect of visual field condition on kinetic in upper extremities and e.m.g in lower extremities while performing reaching in normal adults.

[Purpose] The aims of this study was to investigate mean velocity and angle of shoulder joint, activation of tibialis anterior and gastrocnemius according to both eyes, dominant eye and non-dominant eye condition during reaching task in normal adults. [Subjects and Methods] Our research recruited 24 participants (male 11, female 13) in Silla University. Participants were performed reaching out movement by conditions of both eye, dominants eye, non-dominants eye. The target was placed at 45 degree diagonal direction and distance far away 130% of their arm length. Kinetic analysis of the upper extremities was investigated by QUALISYS 3-dimensional motion analysis system. Muscle activation were measured by EMG during reaching tasks. The collected data were statistically processed using the SPSS for win version 20.0. [Results] There was a significant difference of shoulder joint velocity of flexion, abduction and internal rotation according to visual field condition during reaching tasks. There was no significant difference of shoulder joint angle and muscle activation according to visual field conditions during reaching tasks. [Conclusion] In conclusion, visual field has an influence on shoulder joint velocity. Therefore, the visual field may be to play an important role in reach performance.

A study of the development of the Korean version of PedsQL(TM) 3.0 cerebral palsy module and reliability and validity.

[Purpose] The purpose of this study was to develop the Korean version of the PedsQL(TM) 3.0 Cerebral Palsy Module to evaluate the health-related quality of life of children with cerebral palsy and to test the reliability and validity. [Subjects and Methods] The study included 108 caregivers of children with cerebral palsy aged 2 to 4 years and 72 caregivers of children aged 5 to 7 years, who visited multiple sites between February and August 2015. The Translation Commission performed the first translation with the approval of the Mapi Research Trust Company to create a Korean-version of the PedsQL(TM). Afterwards, back-translation was performed by one translator specializing in health and medical treatment who was a native English-speaker fluent in Korean, and one native Korean-speaker fluent in English. The consistency of each question was confirmed and a translation-integrated version was created. Test components were explained to caregivers during a one-on-one interview; caregivers then completed the PedsQL(TM) questionnaire and a Pediatric Evaluation Disability Inventory (PEDI) questionnaire. Subjects contributing to test-retest measures were asked to repeat the PedsQL questionnaire one week later and return it by mail. To assess data quality for the survey question results, non-response rate, ceiling effect, and floor effect were analyzed. Test-retest reliability and internal consistency reliability were assessed. For test-retest reliability, an intraclass correlation coefficient (ICC) was calculated, and for internal consistency reliability, Cronbach's alpha was used. To test criterion-related validity, Pearson's correlation coefficient was used. [Results] The content validity of the PedsQL 3.0 Cerebral Palsy Module was high for both age groups, and demonstrated significant internal consistency (>0.7) in all areas. For test-retest reliability, both groups demonstrated a significant ICC (>0.61). Correlation with the PEDI was statistically significant in all areas except pain and hurt. [Conclusion] The Korean version of the PedsQL(TM) 3.0 Cerebral Palsy Module was found to be reliable and valid, and is expected to contribute greatly to the evaluation of the quality of life of children with cerebral palsy.

Is there an agreement among the items of the Korean physical therapist licensing examination, learning objectives of class subjects, and physical therapists' job descriptions?

PURPOSE: To determine the agreement among the items of the Korean physical therapist licensing examination, learning objectives of class subjects, and physical therapists' job descriptions. METHODS: The main tasks of physical therapists were classified, and university courses related to the main tasks were also classified. Frequency analysis was used to determine the proportions of credits for the classified courses out of the total credits of major subjects, exam items related to the classified courses out of the total number of exam items, and universities that offer courses related to the Korean physical therapist licensing examination among the surveyed universities. RESULTS: The proportions of credits for clinical decision making and physical therapy diagnosis-related courses out of the total number credits for major subjects at universities were relatively low (2.06% and 2.58%, respectively). Although the main tasks of physical therapists are related to diagnosis and evaluation, the proportion of physiotherapy intervention-related items (35%) was higher than that of examination and evaluation-related items (25%) on the Korean physical therapist licensing examination. The percentages of universities that offer physical therapy diagnosis and clinical decision making-related courses were 58.62% and 68.97%, respectively. CONCLUSION: Both the proportion of physiotherapy diagnosis and evaluation-related items on the Korean physical therapist licensing examination, and the number of subjects related to clinical decision making and physical therapy diagnosis in the physical therapy curriculum, should be increased to ensure that the examination items and physical therapy curriculum reflect the practical tasks of physical therapists.

The Effects of Abdominal Hollowing in Lower-limb PNF Pattern Training on the Activation of Contralateral Muscles.

[Purpose] The purpose of this study was to determine the effects of abdominal hollowing during lower-limb proprioceptive neuromuscular facilitation (PNF) training on the activation of contralateral muscles. [Subjects] Twenty male college students without symptoms or signs of muscular or nervous disease participated in this experiment after signing a consent form. [Methods] All the subjects were measured with electromyography (EMG) in a muscle activation test before and after abdominal hollowing. In the PNF program, the lower-limb pattern of PNF training, was maintained for 5 seconds, followed by a 2-minute break. This was repeated three times. The resting time between sets was 30 minutes. Surface EMG (Keypoint, Medtronic Inc., USA) was used for the measurements, and the highest value of three measurements was used in the analysis. [Result] The results revealed a significant change in the muscular activation of the opposite-side lower limbs. The muscular activations of the vastus lateralis, tibialis anterior, semitendinosus and gastrocnemius were increased significantly after the abdominal hollowing. [Conclusion] The findings suggest that abdominal hollowing in PNF pattern training can be effective at promoting muscular activation of the contralateral muscles. To promote muscular activation of the opposite side in lower-limb PNF pattern training, abdominal hollowing should be considered to improve the effect of PNF pattern training.

Eupatilin inhibits T-cell activation by modulation of intracellular calcium flux and NF-kappaB and NF-AT activity.

Eupatilin, one of the pharmacologically active ingredients of Artemisia princeps, exhibits a potent anti-ulcer activity, but its effects on T-cell immunity have not been investigated. Here, we show that eupatilin has a profound inhibitory effect on IL-2 production in Jurkat T cells as well as in human peripheral blood leukocytes. Eupatilin neither influenced clustering of CD3 and LFA-1 to the immunological synapse nor inhibited conjugate formation between T cells and B cells in the presence or absence of superantigen (SEE). Eupatilin also failed to inhibit T-cell receptor (TCR) internalization, thereby, suggesting that eupatilin does not interfere with TCR-mediated signals on the membrane proximal region. In unstimulated T cells, eupatilin significantly induced apoptotic cell death, as evidenced by an increased population of annexin V(+)/PI(+) cells and cleavage of caspase-3 and PARP. To our surprise, however, once cells were activated, eupatilin had little effect on apoptosis, and instead slightly protected cells from activation-induced cell death, suggesting that apoptosis also is not a mechanism for eupatilin-induced T-cell suppression. On the contrary, eupatilin dramatically inhibited I-kappaBalpha degradation and NF-AT dephosphorylation and, consequently, inhibited NF-kappaB and NF-AT promoter activities in PMA/A23187-stimulated T cells. Interestingly, intracellular calcium flux was significantly perturbed in cells pre-treated with eupatilin, suggesting that calcium-dependent cascades might be targets for eupatilin action. Collectively, our results provide evidence for dual regulatory functions of eupatilin: (1) a pro-apoptotic effect on resting T cells and (2) an immunosuppressive effect on activated T cells, presumably through modulation of Ca(2+) flux.

Eupatilin exhibits a novel anti-tumor activity through the induction of cell cycle arrest and differentiation of gastric carcinoma AGS cells.

In many cases, the process of cancer cell differentiation is associated with the programmed cell death. In the present study, interestingly, we found that eupatilin, one of the pharmacologically active ingredients of Artemisia asiatica that has been reported to induce apoptosis in human gastric cancer AGS cells, also triggers differentiation of these cells. Treatment of AGS cells with eupatilin induced cell cycle arrest at the G(1) phase with the concomitant induction of p21(cip1), a cell cycle inhibitor. This led us to test whether eupatilin may trigger AGS cells to differentiate into the matured phenotypes of epithelial cells and this phenomenon may be coupled to the apoptosis. Eupatilin induced changes of AGS cells to a more flattened morphology with increased cell size, granularity, and mitochondrial mass. It also markedly induced trefoil factor 1 (TFF1), a gene responsible for the gastrointestinal cell differentiation. Eupatilin dramatically induced redistribution of tight junction proteins such as occludin and ZO-1, and F-actin at the junctional region between cells. It also induced phosphorylation of extracellular signal-regulated kinase 2 and p38 kinase. Blockade of ERK signaling by PD098059 or the dominant-negative ERK2 significantly reduced eupatilin-induced TFF1 and p21 expression as well as ZO-1 redistribution, indicating that ERK cascades may mediate eupatilin-induced AGS cell differentiation. Collectively, our results suggest that eupatilin acts as a novel anti-tumor agent by inducing differentiation of gastrointestinal cancer cells rather than its direct role in inducing apoptotic cell death.

Chemopreventive effects of the standardized extract (DA-9601) of Artemisia asiatica on azoxymethane-initiated and dextran sulfate sodium-promoted mouse colon carcinogenesis.

Dextran sulfate sodium (DSS) administration has been reported to cause inflammation in mouse colonic mucosa, which promotes colon carcinogenesis. When male ICR mice were treated with a single intraperitoneal dose (10 mg/kg body weight) of azoxymethane (AOM) followed by 2.5% DSS in drinking water for 7 consecutive days, all developed tumors at the 16th wk, mostly in the distal colon. Cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) were markedly upregulated in the AOM-initiated and DSS-promoted colon tumors. The DNA binding activity of nuclear factor-kappaB (NF-kappa B) was also elevated in the colon tumors. In this study, we examined the chemopreventive effects of the standardized extract (DA-9601) of Artemisia asiatica that has been used in the traditional herbal medicine for the treatment of inflammatory disorders. Mice fed the chow diet containing 10% DA-9601 for 15 wk following DSS treatment displayed the significantly lower multiplicity of colon tumors. DA-9601 treatment suppressed the expression of COX-2 and iNOS as well as NF-kappa B DNA binding in the colonic tissues. It also downregulated the phosphorylation of extracellular, signal-regulated protein kinase and p38 mitogen-activated protein kinase that are upstream of NF-kappa B. Furthermore, DA-9601 reduced expression of beta-catenin in colonic mucosa of mice challenged with AOM plus DSS.

Eupatilin protects gastric epithelial cells from oxidative damage and down-regulates genes responsible for the cellular oxidative stress.

PURPOSE: The formulated ethanol extract (DA-9601) of Artemisia asiatica has pronounced antiinflammatory activities and exhibits cytoprotective effects against gastrointestinal damage. Here we investigated whether eupatilin, a major component of DA-9601, has a property of antioxidant activity and protects gastric epithelial cells from H2O2-induced damage. Methods. METHODS: epithelial AGS cells by measuring wound healing, cell proliferation, and cell viability. Global gene expression profiling was obtained by high-density microarray. RESULTS: Hydrogen peroxide significantly delayed epithelial migration in wounded area. In contrast, eupatilin prevented the reduction of epithelial migration induced by H2O2. Eupatilin also ameliorated H2O2-induced actin disruption in AGS cells. Interestingly, treatment with eupatilin dramatically inhibited FeSO4-induced ROS production in a dose-dependent manner. In addition, eupatilin protected cells from FeSO4-induced F-actin disruption. With high-density microarray, we identified dozens of genes whose expressions were up-regulated in H2O2-treated cells. We found that eupatilin reduces the expression of such oxidative-responsible genes as HO-1, PLAUR and TNFRSF10A in H2O2-treated cells. CONCLUSION: These results suggest that eupatilin acts as a novel antioxidant and may play an important role in DA-9601-mediated effective repair of the gastric mucosa.

DA-9601, a standardized extract of Artemisia asiatica, blocks TNF-alpha-induced IL-8 and CCL20 production by inhibiting p38 kinase and NF-kappaB pathways in human gastric epithelial cells.

AIM: To investigate whether, or how, DA-9601, which is a new gastroprotective agent, inhibits TNF-alpha-induced inflammatory signals in gastric epithelial AGS cells. METHODS: Cell viability was determined by MTT assay. IL-8 and CCL20 promoter activities were determined by a luciferase reporter gene assay. NF-kappaB-dependent transcriptional activity was determined by I-kappaB alpha degradation, NF-kappaB p65 nuclear translocation and a luciferase activity assay. IL-8 and CCL20 gene expression and protein secretion were determined by RT-PCR and an enzyme-linked immunosorbent assay (ELISA). Total and phosphorylated forms of mitogen-activated protein kinases (MAPKs) were determined by Western blot. RESULTS: Treatment of AGS cells with DA-9601 reduced TNF-alpha-induced IL-8 and CCL20 promoter activities, as well as their gene expression and protein release. TNF-alpha also induced NF-kappaB-dependent transcriptional activity in AGS cells. In contrast, in cells treated with DA-9601, TNF-alpha-induced NF-kappaB activity was significantly blocked. Although all three MAP kinase family members were phosphorylated in response to TNF-alpha, a selective inhibitor of p38 kinase SB203580 only could inhibit both NF-kappaB-dependent transcriptional activity and IL-8 and CCL20 production, suggesting a potential link between p38 kinase and NF-kappaB-dependent pathways in AGS cells. Interestingly, DA-9601 also selectively inhibited p38 kinase phosphorylation induced by TNF-alpha. CONCLUSION: DA-9601 blocked TNF-alpha-mediated inflammatory signals by potentially modulating the p38 kinase pathway and/or a signal leading to NF-kappaB-dependent pathways in gastric epithelial cells.

Protective effects of green tea polyphenol extracts against ethanol-induced gastric mucosal damages in rats: stress-responsive transcription factors and MAP kinases as potential targets.

There are multiple lines of compelling evidence from epidemiologic and laboratory studies supporting that frequent consumption of green tea is inversely associated with the risk of chronic human diseases including cancer. The chemopreventive and chemoprotective effects of green tea have been largely attributed to antioxidative and anti-inflammatory activities of its polyphenolic constituents, such as epigallocatechin gallate. The present study was designed to evaluate the efficacy of green tea polyphenols in protecting against alcohol-induced gastric damage and to elucidate the underlying mechanisms. Intragastric administration of ethanol to male Sprague-Dawley rats caused significant gastric mucosal damage, which was accompanied by elevated expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) as well as transient activation of redox-sensitive transcription factors, such as NF-kappaB and AP-1, and mitogen-activated protein kinases (MAPKs). Oral administration of the green tea polyphenolic extract (GTE) significantly ameliorated mucosal damages induced by ethanol and also attenuated the ethanol-induced expression of COX-2 and iNOS. Inactivation of MAPKs, especially p38 and ERKl/2, by GTE might be responsible for inhibition of ethanol-induced expression of COX-2 and iNOS.

Novel antioxidant ameliorates the fibrosis and inflammation of cerulein-induced chronic pancreatitis in a mouse model.

BACKGROUND/AIM: Oxygen free radicals (OFRs) mediate an important step in the initiation of experimental acute pancreatitis and several clinical findings suggested the possible contribution of OFRs to the pathogenesis of pancreatic fibrosis. So far, there are no studies which reporting potential role of OFRs in development of chronic pancreatitis with the prevention with antioxidants. This study was aimed to establish the mice model of chronic fibrosing pancreatitis and to prove the involvement of OFRs in chronic pancreatitis with fibrosis. METHODS: Repeated intraperitoneal cerulein injection was performed to induce chronic pancreatitis in mice. Histological changes in the pancreas were examined, and markers for oxidative stress were measured in the pancreatic tissue and serum of the mice. DA-9601, a phytochemical possessing anti-inflammatory and antioxidative action, was given together with cerulein to the mice. RESULTS: Repeated intraperitoneal injection of cerulein provoked significant severity of chronic fibrosing pancreatitis after 5 weeks. After treatment of DA-9601, the extents of pancreatic fibrosis were statistically significantly decreased in accordance with lessened pancreatic inflammations. The NF-kappaB binding activities were increased in chronic pancreatitis, which were significantly attenuated after DA-9601 treatment. The levels of myeloperoxidase and iNOS activities were also significantly decreased in DA-9601-treated group compared to the pancreatitis only group. Cytoprotective proteins such as heat shock protein-70 (HSP) and metallothionein were significantly increased in the DA-9601-treated group. DA-9601 decreased the expressions of alpha-SMA and type I collagen in cultured pancreatic stellate cells. CONCLUSIONS: Oxidative stress was principally involved in the pathogenesis of chronic pancreatitis with fibrosis.

Preventive effect of the flavonoid, wogonin, against ethanol-induced gastric mucosal damage in rats.

Whether wogonin (5,7-dihydroxy-8-methoxyflavone), a flavonoid originated from the root of Scutellaria baicalensis Georgi, which has been shown to have antiinflammatory and antitumor activities in various cell types, possesses a gastric cytoprotective effect was investigated in an ethanol-induced gastric damage model in rats. Ethanol administration alone induced evident gastric damage including gastric hemorrhages and edema, while this gastric damage was significantly attenuated by wogonin pretreatment (30 mg/kg B.W.) 1 hr before ethanol administration. As major protective mechanisms of wogonin on ethanol-induced gastric damage, we found that wogonin showed either antiinflammatory effects through dual actions on arachidonic acid metabolism, i.e., induction of prostaglandin D2 and suppression of 5S-hydroxyeicosatetraenoic acid (5S-HETE), or preventive induction of profuse apoptosis in the stomach. Conclusively, the flavonoid wogonin could be used as a preventive agent of alcohol-induced gastropathy, whose actions were proven to be strong antiinflammation and apoptosis induction.