Effect of a New Prokinetic Agent DA-9701 Formulated with Corydalis Tuber and Pharbitidis Semen on Cytochrome P450 and UDP-Glucuronosyltransferase Enzyme Activities in Human Liver Microsomes

DA-9701 is a new botanical drug composed of the extracts of Corydalis tuber and Pharbitidis semen, and it is used as an oral therapy for the treatment of functional dyspepsia in Korea. The inhibitory potentials of DA-9701 and its component herbs, Corydalis tuber and Pharbitidis semen, on the activities of seven major human cytochrome P450 (CYP) enzymes and four UDP-glucuronosyltransferase (UGT) enzymes in human liver microsomes were investigated using liquid chromatography-tandem mass spectrometry. DA-9701 and Corydalis tuber extract slightly inhibited UGT1A1-mediated etoposide glucuronidation, with 50% inhibitory concentration (IC50) values of 188 and 290 μg/mL, respectively. DA-9701 inhibited CYP2D6-catalyzed bufuralol 1′-hydroxylation with an inhibition constant (Ki) value of 6.3 μg/mL in a noncompetitive manner. Corydalis tuber extract competitively inhibited CYP2D6-mediated bufuralol 1′-hydroxylation, with a Ki value of 3.7 μg/mL, whereas Pharbitidis semen extract showed no inhibition. The volume in which the dose could be diluted to generate an IC50 equivalent concentration (volume per dose index) value of DA-9701 for inhibition of CYP2D6 activity was 1.16 L/dose, indicating that DA-9701 may not be a potent CYP2D6 inhibitor. Further clinical studies are warranted to evaluate the in vivo extent of the observed in vitro interactions

Physician Compliance with Nutrition Support Team Recommendations: Effects on the Outcome of Treatment for Critically Ill Patients

Purpose Attending physicians in Korea are aware of the existence of the Nutrition Support Team (NST), but even when the NST are consulted, compliance with their recommendations may be low. This study was performed to identify physicians’ compliance with the NST advice and how this affected the outcome of treatment for critically ill patients. Methods This study was a retrospective observational study. Critically ill patients who were older than 18 years, younger than 90 years, and had been admitted and managed in the intensive care unit were selected for this study. Patients were assigned to either the compliance group or the non-compliance group according to physician compliance with the NST advice. Each group were compared using variables such as calorie supply, protein supply, laboratory findings, hospital stay, 30-day mortality, and survival rate. Results The compliance group (81% of cases) was supplied with a significantly higher energy (1,146.36 ± 473.45 kcal vs. 832.45 ± 364.28 kcal, p < 0.01) and a significantly higher protein (55.00 ± 22.30 g/day vs. 42.98 ± 24.46 g/day, p = 0.04) compared with the non-compliance group. There was no significant difference in the basic demographics between groups, although the compliance group had a better outcome in the 30-day mortality rate (8% vs. 26%, p = 0.02), and in survival beyond 1 year (Crude model, hazard ratio: 2.42, CI: 1.11–5.29). Conclusion Critically ill patients whose attending physician complied with the NST advice, received an increased energy intake and supply of protein which was positively associated with survival

Effect of software version and parameter settings on the marginal and internal adaptation of crowns fabricated with the CAD/CAM system

Objective This study investigated the marginal and internal adaptation of individual dental crowns fabricated using a CAD/CAM system (Sirona’s BlueCam), also evaluating the effect of the software version used, and the specific parameter settings in the adaptation of crowns.Material and Methods Forty digital impressions of a master model previously prepared were acquired using an intraoral scanner and divided into four groups based on the software version and on the spacer settings used. The versions 3.8 and 4.2 of the software were used, and the spacer parameter was set at either 40 μm or 80 μm. The marginal and internal fit of the crowns were measured using the replica technique, which uses a low viscosity silicone material that simulates the thickness of the cement layer. The data were analyzed using a Friedman two-way analysis of variance (ANOVA) and paired t-tests with significance level set at

Sulforaphane Increases Cyclin-Dependent Kinase Inhibitor, p21 Protein in Human Oral Carcinoma Cells and Nude Mouse Animal Model to Induce G2/M Cell Cycle Arrest

Previously, our group reported that sulforaphane (SFN), a naturally occurring chemopreventive agent from cruciferous vegetables, effectively inhibits the proliferation of KB and YD-10B human oral squamous carcinoma cells by causing apoptosis. In this study, treatment of 20 and 40 µM of SFN for 12 h caused a cell cycle arrest in the G2/M phase. Cell cycle arrest induced by SFN was associated with a significant increase in the p21 protein level and a decrease in cyclin B expression, but there was no change in the cyclin A protein level. In addition, SFN increased the p21 promoter activity significantly. Furthermore, SFN induced p21 protein expression in a nude mouse xenograft model suggesting that SFN is a potent inducer of the p21 protein in human oral squamous carcinoma cells. These findings show that SFN is a promising candidate for molecular-targeting chemotherapy against human oral squamous cell carcinoma

Combined spinal-epidural anesthesia for cesarean section in a patient with Moyamoya disease -A case report-

Moyamoya disease is a rare progressive occlusive disease of the internal carotid arteries. We report a case of combined spinal-epidural anesthesia in a patient with Moyamoya disease presenting for Cesarean section. Hypotension associated with spinal anesthesia for Cesarean section is the most common and serious adverse effect despite the use of uterine displacement and volume preload. We continuously infused phenylephrine and ephedrine to prevent hypotension. The intraoperative hemodynamic state was stable. The patient had no significant postoperative complications

Intranasal immunization with plasmid DNA encoding spike protein of SARS-coronavirus/polyethylenimine nanoparticles elicits antigen-specific humoral and cellular immune responses

<p>Abstract</p> <p>Background</p> <p>Immunization with the spike protein (S) of severe acute respiratory syndrome (SARS)-coronavirus (CoV) in mice is known to produce neutralizing antibodies and to prevent the infection caused by SARS-CoV. Polyethylenimine 25K (PEI) is a cationic polymer which effectively delivers the plasmid DNA.</p> <p>Results</p> <p>In the present study, the immune responses of BALB/c mice immunized via intranasal (i.n.) route with SARS DNA vaccine (pci-S) in a PEI/pci-S complex form have been examined. The size of the PEI/pci-S nanoparticles appeared to be around 194.7 ± 99.3 nm, and the expression of the S mRNA and protein was confirmed <it>in vitro</it>. The mice immunized with i.n. PEI/pci-S nanoparticles produced significantly (<it>P </it>< 0.05) higher S-specific IgG1 in the sera and mucosal secretory IgA in the lung wash than those in mice treated with pci-S alone. Compared to those in mice challenged with pci-S alone, the number of B220⁺cells found in PEI/pci-S vaccinated mice was elevated. Co-stimulatory molecules (CD80 and CD86) and class II major histocompatibility complex molecules (I-A^d) were increased on CD11c⁺dendritic cells in cervical lymph node from the mice after PEI/pci-S vaccination. The percentage of IFN-γ-, TNF-α- and IL-2-producing cells were higher in PEI/pci-S vaccinated mice than in control mice.</p> <p>Conclusion</p> <p>These results showed that intranasal immunization with PEI/pci-S nanoparticles induce antigen specific humoral and cellular immune responses.</p

Functional Recapitulation of Smooth Muscle Cells Via Induced Pluripotent Stem Cells From Human Aortic Smooth Muscle Cells

Rationale: Generation of induced pluripotent stem (iPS) cells has been intensively studied by a variety of reprogramming methods, but the molecular and functional properties of the cells differentiated from iPS cells have not been well characterized. Objective: To address this issue, we generated iPS cells from human aortic vascular smooth muscle cells (HASMCs) using lentiviral transduction of defined transcription factors and differentiated these iPS cells back into smooth muscle cells (SMCs). Methods and Results: Established iPS cells were shown to possess properties equivalent to human embryonic stem cells, in terms of the cell surface markers, global mRNA and microRNA expression patterns, epigenetic status of OCT4, REX1, and NANOG promoters, and in vitro/in vivo pluripotency. The cells were differentiated into SMCs to enable a direct, comparative analysis with HASMCs, from which the iPS cells originated. We observed that iPS cell-derived SMCs were very similar to parental HASMCs in gene expression patterns, epigenetic modifications of pluripotency-related genes, and in vitro functional properties. However, the iPS cells still expressed a significant amount of lentiviral transgenes (OCT4 and LIN28) because of partial gene silencing. Conclusions: Our study reports, for the first time, the generation of iPS cells from HASMCs and their differentiation into SMCs. Moreover, a parallel comparative analysis of human iPS cell-derived SMCs and parental HASMCs revealed that iPS-derived cells possessed representative molecular and in vitro functional characteristics of parental HASMCs, suggesting that iPS cells hold great promise as an autologous cell source for patient-specific cell therapy. (Circ Res. 2010;106:120-128.)Yu JY, 2007, SCIENCE, V318, P1917, DOI 10.1126/science.1151526Hanna J, 2007, SCIENCE, V318, P1920, DOI 10.1126/science.1152092Takahashi K, 2007, CELL, V131, P861, DOI 10.1016/j.cell.2007.11.019Byrne JA, 2007, NATURE, V450, P497, DOI 10.1038/nature06357Lee TH, 2007, PLOS MED, V4, P1101, DOI 10.1371/journal.pmed.0040186Matsumura H, 2007, NAT METHODS, V4, P23, DOI 10.1038/NMETH973Aoi T, 2008, SCIENCE, V321, P699, DOI 10.1126/science.1154884Dimos JT, 2008, SCIENCE, V321, P1218, DOI 10.1126/science.1158799Barroso-delJesus A, 2008, MOL CELL BIOL, V28, P6609, DOI 10.1128/MCB.00398-08Aasen T, 2008, NAT BIOTECHNOL, V26, P1276, DOI 10.1038/nbt.1503Stadtfeld M, 2008, SCIENCE, V322, P945, DOI 10.1126/science.1162494Okita K, 2008, SCIENCE, V322, P949, DOI 10.1126/science.1164270Tateishi K, 2008, J BIOL CHEM, V283, P31601, DOI 10.1074/jbc.M806597200Zhang JH, 2009, CIRC RES, V104, pE30, DOI 10.1161/CIRCRESAHA.108.192237Soldner F, 2009, CELL, V136, P964, DOI 10.1016/j.cell.2009.02.013Chang SA, 2008, STEM CELLS, V26, P1901, DOI 10.1634/stemcells.2007-0708Park IH, 2008, NATURE, V451, P141, DOI 10.1038/nature06534Lowry WE, 2008, P NATL ACAD SCI USA, V105, P2883, DOI 10.1073/pnas.0711983105Laurent LC, 2008, STEM CELLS, V26, P1506, DOI 10.1634/stemcells.2007-1081Kim JB, 2008, NATURE, V454, P646, DOI 10.1038/nature07061Ross JJ, 2006, J CLIN INVEST, V116, P3139, DOI 10.1172/JCI28184Takahashi K, 2006, CELL, V126, P663Yu JY, 2006, STEM CELLS, V24, P168, DOI 10.1634/stemcells.2005-0292Cowan CA, 2005, SCIENCE, V309, P1369, DOI 10.1126/science.1116447Adhikary S, 2005, NAT REV MOL CELL BIO, V6, P635, DOI 10.1038/nrm1703DALLAFAVERA R, 1982, P NATL ACAD SCI-BIOL, V79, P78241

A Prospective Multi-center Trial of Escherichia coli Extract for the Prophylactic Treatment of Patients with Chronically Recurrent Cystitis

We have assessed the efficacy and safety of Escherichia coli extract (ECE; UroVaxom (R)) which contains active immunostimulating fractions, in the prophylactic treatment of chronically recurrent cystitis. Forty-two patients with more than 2 episodes of cystitis in the proceeding 6 months were treated for 3 months with one capsule daily of ECE and observed for a further 6 months. The primary efficacy criterion was the number of episodes of recurrent cystitis during the 6 months after treatment compared to those during the 6 months before treatment. At the end of the 9-month trial, 34 patients (all women) were eligible for statistical analysis. Their mean age was 56.4 yr (range, 34-75 yr), and they had experienced recurrent urinary tract infections for 7.2 +/- 5.2 yr. The number of recurrences was significantly lower during the 6-month follow-up period than during the 6 months preceding the trial (0.35 vs. 4.26, P<0.001). During the follow-up, 28 (82.4%) patients had no recurrences and 4 (11.8%) had 1 each. In patients who relapsed, ECE alleviated cystitis symptoms, including painful voiding, frequency and urgency. There were no serious adverse events related to the study drug. Our study demonstrates the efficacy and safety of ECE in the prophylactic treatment of chronically recurrent cystitis.Ha US, 2008, INT J ANTIMICROB AG, V31, pS63, DOI 10.1016/j.ijantimicag.2007.07.018LEE SJ, 2008, KOREAN J UROL, V48, P428Krieger JN, 2002, J UROLOGY, V168, P2351, DOI 10.1097/01.ju.0000037620.30988.b2Barnett BJ, 1997, AM J MED SCI, V314, P245Nicolle LE, 1997, INFECT DIS CLIN N AM, V11, P647Baier W, 1997, ARZNEIMITTEL-FORSCH, V47, P980Lettgen B, 1996, CURR THER RES CLIN E, V57, P464AVORN J, 1994, JAMA-J AM MED ASSOC, V271, P751MAGASI P, 1994, EUR UROL, V26, P137SCHULMAN CC, 1993, J UROLOGY, V150, P917JACOBY GA, 1991, NEW ENGL J MED, V324, P601NAUCK M, 1991, INT J EXP CLIN CHEMO, V4, P1SOTOLONGO JR, 1990, J UROLOGY, V143, P979VANPHAM T, 1990, J BIOL RESP MODIF, V9, P231TAMMEN H, 1990, BRIT J UROL, V65, P6HANSSON S, 1989, BRIT MED J, V298, P856HANSSON S, 1989, BRIT MED J, V298, P853WYBRAN J, 1989, IMMUNOPHARM IMMUNOT, V11, P17BOSCH A, 1988, IMMUNOPHARM IMMUNOT, V10, P333TAMMEN H, 1988, UROLOGE, V28, P294BOTTEX C, 1988, INT J IMMUNOTHER, V4, P203FREY C, 1986, UROL INT, V41, P444HAUSER WE, 1982, AM J MED, V72, P711