The effects of thermal softening of double-lumen endobronchial tubes on postoperative sore throat, hoarseness and vocal cord injuries: a prospective double-blind randomized trial.

BACKGROUND: It is well known that thermal softening of polyvinyl chloride tracheal tubes reduces nasal damage during nasotracheal intubation. We hypothesized that thermal softening of double-lumen endobronchial tubes (DLTs) may be effective for reducing airway injury. This randomized double-blind study was performed to investigate whether thermal softening of DLTs decreased postoperative sore throat, hoarseness or vocal cord injuries. METHODS: Patients (n=140) undergoing one lung anaesthesia were randomized into two groups (n=70 each) depending on whether the DLT was softened by warming or not before tracheal intubation. The DLTs were placed in warm saline [40(1)°C] in the thermal softening group or in room temperature saline in the control group for 10 min. The vocal cords were examined by using flexible laryngoscopy immediately after extubation. Sore throat and hoarseness were evaluated for three postoperative days. The primary outcomes were the incidence of sore throat, hoarseness, and vocal cord injuries. RESULTS: Sore throat and vocal cord injuries occurred less frequently in the thermal softening group than in the control group [14/70 vs 27/70, risk ratio (95% CI): 0.52 (0.30-0.90), P=0.025 for sore throat; 15/70 vs 27/70, risk ratio (95% CI): 0.56 (0.32-0.95), P=0.042 for vocal cord injuries]. However, the incidence of hoarseness was comparable between the two groups. CONCLUSION: Tracheal intubation with DLTs softened by warming decreased the postoperative incidence of sore throat and vocal cord injuries. Therefore, thermal softening of DLTs before intubation seems to be helpful in reducing airway injuries associated with DLT intubation. CLINICAL TRIAL REGISTRATION: NCT 01626365.

In vitro and in vivo immunostimulatory activity of an exopolysaccharide-enriched fraction from Bacillus subtilis.

AIMS: The aim of this study was to investigate the immunostimulatory effects of an exopolysaccharide-enriched fraction obtained from Bacillus subtilis J92 (B-EPS). METHODS AND RESULTS: To determine the immunostimulatory activities of B-EPS, we used IFN-γ-primed RAW 264.7 macrophages and CD3/CD28-stimulated splenocytes. Increases in the levels of NO and many cytokines, such as, TNF-α, IL-6, and IL-1ß, were observed in IFN-γ-primed RAW 264.7 macrophages by Griess reaction and ELISAs respectively. Using Western blotting and qRT-PCR, we found that B-EPS increased the protein and mRNA expressions of iNOS and the mRNA expressions of TNF-α, IL-6, and IL-1ß. A reporter gene assay and EMSA revealed that B-EPS up-regulated the transcriptional activity of NF-κB by increasing its DNA binding and nuclear translocation. Pretreatment with NF-κB inhibitors, that is, BAY11-7082 and PDTC, decreased NO production in IFN-γ-primed RAW 264.7 macrophages by B-EPS. Furthermore, B-EPS increased the proliferation of and cytokine (IL-2 and IFN-γ) production by CD3/CD28-stimulated splenocytes. In a cyclophosphamide-induced immunosuppressed mouse model, B-EPS (5, 15 or 45 mg kg(-1) , p.o.) restored thymus and spleen indices. B-EPS also inhibited cyclophosphamide-induced reductions in neutrophil and lymphocyte numbers. CONCLUSIONS: B-EPS improves immune function by regulating immunological parameters in IFN-γ-primed macrophages, CD3/CD28-stimulated splenocytes, and in cyclophosphamide-induced immunosuppressed mice. SIGNIFICANCE AND IMPACT OF THE STUDY: This study suggests that the exopolysaccharides secreted by B. subtilis J92 could be used as immune stimulants.

Magnon gap excitations in van der Waals antiferromagnet MnPSe3.

Magneto-spectroscopy methods have been employed to study the zero-wavevector magnon excitations in MnPSe3. Experiments carried out as a function of temperature and the applied magnetic field show that two low-energy magnon branches of MnPSe3 in its antiferromagnetic phase are gapped. The observation of two low-energy magnon gaps (at 1.70 ± 0.05 meV and 0.09 ± 0.01 meV) implies that MnPSe3 is a biaxial antiferromagnet. A relatively strong out-of-plane anisotropy imposes the spin alignment to be in-plane whereas the spin directionality within the plane is governed by a factor of 2.5 × 10-3 weaker in-plane anisotropy.

Comparison of Posttransplant Outcomes in Living Donor Liver Transplantation for Obese and Nonobese Recipients.

BACKGROUND: Although living donor liver transplantation for obese recipients has increased, it has not been determined that posttransplant outcomes in obese recipients are inferior compared with nonobese recipients. METHODS: From January 2001 to December 2016, there was a total of 58 (6%) obese patients (body mass index ≥30) in a cohort of 973 adult patients that underwent living donor liver transplantation. Propensity score matching and classification were performed based on the type of obesity, and there were 58 patients in the obese group and 141 patients in the nonobese group. We performed comparative analysis of posttransplant outcomes including Model for Early Allograft Function (MEAF) scoring and early allograft dysfunction (EAD). RESULTS: EAD was found in 11 (19%) and 31 (22%) patients in the obese and nonobese groups, respectively (P = .71). The obese group had a higher MEAF score than the nonobese group (5.2 vs 4.5, P = .007). The mean hospitalization of the obese group was shorter than in the nonobese group (32 vs 42 days, P = .003). Other posttransplant outcomes were similar between the obese and nonobese groups, including acute cellular rejection (8 vs 10 cases, P = .17), early graft failure (8 vs 12 cases, P = .30), index hospital mortality (6 vs 11 cases, P = .58), and comprehensive complication index (26.0 vs 24.6, P = .76). CONCLUSION: Posttransplant outcomes of the obese group were not inferior to the nonobese group. However, obesity can impact the severity of EAD and the incidence of early graft failure, based on significantly higher MEAF scores.

Comparative Analysis of the Clinical Outcomes of Liver Transplantation for Probable and Definite Auto-immune Hepatitis by International Diagnostic Scoring Criteria.

BACKGROUND: Liver transplantation (LT) is an effective treatment for patients with end-stage liver disease caused by auto-immune hepatitis (AIH). However, diagnosis of AIH can be challenging for patients with end-stage liver disease at the time of transplantation. We classified patients into "probable" or "definite" AIH groups, using the diagnostic criteria of the International Autoimmune Hepatitis Group, and compared the clinical outcomes of AIH after LT in these 2 groups. METHODS: We performed a retrospective study of 18 patients who were diagnosed with AIH and underwent LT from March 2003 to March 2015 at a single institute. Of the 18 patients, 8 were diagnosed with definite AIH and 10 were diagnosed with probable AIH, according to the international scoring criteria. We evaluated the patient characteristics, recurrence rate, graft loss, and survival rates after LT. RESULTS: The mean follow-up duration was 59.3 months. Age, sex, medical condition at transplantation, warm ischemic time, cold ischemic time, and Model for End-Stage Liver Disease score did not differ significantly between the 2 groups. No patient died after LT in either group, but 1 patient in the definite AIH group had graft failure. In Kaplan-Meier analysis, the 5-year recurrence rates of the definite and probable groups were 14.3% and 0%, respectively (P = .992). CONCLUSIONS: The recurrence of definite AIH appeared to be higher than that of probable AIH. However, careful immunosuppressive therapy allowed the long-term survival of both definite and probable AIH patients after LT.

Major Histocompatibilty Complex-Restricted Adaptive Immune Responses to CT26 Colon Cancer Cell Line in Mixed Allogeneic Chimera.

BACKGROUND: Although the induction of mixed allogeneic chimera shows promising clinical tolerance results in organ transplantation, its clinical relevance as an anti-cancer therapy is yet unknown. We introduced a mixed allogenic chimera setting with the use of a murine colon cancer cell line, CT26, by performing double bone marrow transplantation. METHODS: We analyzed donor- and recipient-restricted anti-cancer T-cell responses, and phenotypes of subpopulations of T cells. The protocol involves challenging 1 × 105 cells of CT26 cells intra-hepatically on day 50 after bone marrow transplantation, and, by use of CT26 lysates and an H-2Ld-restricted AH1 pentamer, flow cytometric analysis was performed to detect the generation of cancer-specific CD4+ and CD8+ T cells at various time points. RESULTS: We found that immunocompetence against tumors depends heavily on cancer-specific CD8+ T-cell responses in a major histocompatibility complex-restricted manner; the evidence was further supported by the increase of interferon-γ-secreting CD4+ T cells. Moreover, we demonstrated that during the effector immune response to CT26 cancer challenge, there was a presence of central memory cells (CD62LhiCCR7+) as well as effector memory cells (CD62LloCCR7-). Moreover, mixed allogeneic chimeras (BALB/c to C56BL/6 or vice versa) showed similar or heightened immune responses to CT26 cells compared with that of wild-type mice. CONCLUSIONS: Our results suggest that the responses of primary immunocompetency and of pre-existing memory T cells against allogeneic cancer are sustained and preserved long-term in a mixed allogeneic chimeric environment.

Mobility and biodegradability of an imidazolium based ionic liquid in soil and soil amended with waste sewage sludge.

Sorption on solids and biodegradation are main phenomena that can mitigate the pollution of soil and water by ionic liquids (ILs). ILs sorbed on soil particles become immobilized (temporarily or permanently) which prevents them from spreading into deeper layers of soil or groundwater but which also makes them less bioavailable. In this study we attempt to examine if amendment of soil with waste sludge has a potential to mitigate the transport and enhance biodegradation of ILs using 1-methyl-3-octylimidazolium chloride ([OMIM][Cl]) as an example. We present the results of adsorption test (batch and column) and ultimate biodegradation of [OMIM][Cl] using microbial communities derived from soil. Finally, we combine all of these processes together to examine the fate of [OMIM][Cl] in a continuous column flow-through system in soil amended with waste sewage sludge. Addition of sludge serves two purposes: firstly increasing soil organic matter (formerly proved to facilitate retardation), and secondly augmenting soil with versatile microbial communities previously shown to successfully degrade ILs.

Down modulation of IL-18 expression by human papillomavirus type 16 E6 oncogene via binding to IL-18.

To understand modulation of a novel immune-related cytokine, interleukin-18, by human papillomavirus type (HPV) 16 oncogenes, HaCaT, normal keratinocyte cell line, and C-33A, HPV-negative cervical cancer cell line, were prepared to establish stable cell lines expressing E6, E6 mutant (E6m), E6E7, or E7 constitutively. Expressions of various HPV oncogene transcripts were identified by RT-PCR. Expression of HPV oncogene E6 was reversely correlated to the expression of interleukin-18, a novel pro-inflammatory cytokine. The expression of E6 in C-33A, independent of E6 splicing, resulted in decreased IL-18 expression and that of IL-18 was also significantly reduced in HaCaT cells expressing E6. The level of p53 was reduced in C-33A cells expressing E6 whereas not altered in HaCaT cells expressing E6, suggesting that E6 downregulated IL-18 expression via an independent pathway of p53 degradation in HaCaT cells which have a mutated p53 form. However, E7 did not affect IL-18 expression significantly in both C-33A and HaCaT cells. Cotransfection experiments showed that E6 oncogene did not inhibit the activities of IL-18 promoter P1 and P2, suggesting that E6 oncogene indirectly inhibited IL-18 expression. Taken together, E6, E6m and E6/E7 inhibited IL-18 expression with some variation, assuming that cells expressing E6 oncogene can evade immune surveillance by downregulating the expression of immune stimulating cytokine gene, IL-18, and inhibiting the cascade of downstream effects that follow activation of the IL-18 receptor.

Improvement of gene transfer to cervical cancer cell lines using non-viral agents.

Virus-like particles (VLPs) composed of recombinant capsid protein L1 and L2 of human papillomavirus type 16 were conjugated with polylysine (PL) and gene transfer was performed using VLP-PL conjugates to allow the expression of targeted gene. When HeLa cells were incubated with VLP-PL conjugate coupled with plasmid cytomegalovirus beta-galactosidase (pCMVbeta-gal), about 10% of cells were transfected and demonstrated beta-galactosidase activity. Hence chloramphenicol acetyltransferase activity was also expressed significantly in VLP-PL-plasmid simian virus 2 chloramphenicol acetyl transferase (pSV2CAT)-transfected cells, VLP-PL conjugate was tested whether it could transfer a tumor suppressor gene, pCMVp53, to HeLa cells and the exogenously provided p53 gene complexed to VLP-PL conjugate was detected from HeLa cells by polymerase chain reaction (PCR) analysis. Interestingly, additional increase of transfection efficiency was demonstrated in the presence of poloxamer 407 when C-33A cells were transfected with VLP-PL-pCMVbeta-gal complex. The result support the notion that VLP-PL conjugate may be a promising vector to transfer genetic materials into cancer cells and poloxamer 407 can be used for enhancing the transfection efficiency of VLP-PL conjugate.

Effects of non-ionic surfactants as permeation enhancers towards piroxicam from the poloxamer gel through rat skins.

The enhancing effects of non-ionic surfactants on the permeation of piroxicam from the poloxamer gels were evaluated using Franz diffusion cells fitted with excised rat skins. The effectiveness of penetration enhancers, the ratio of piroxicam flux in the presence or absence of enhancers, was defined as the enhancement factor. Among the various non-ionic surfactants tested, polyoxyethylene-2-oleyl ether showed the highest enhancing effects with an enhancement factor of 2.84. To elucidate the mechanisms of the action of enhancers, thermal analysis and histological examinations were carried out. Thermal analysis reveals that various surfactants have different fluidizing effects on stratum corneum. Skin pretreated with the poloxamer 407 gels containing various surfactants showed a loosely layered stratum corneum and wide intercellular space.

In silico modelling for predicting the cationic hydrophobicity and cytotoxicity of ionic liquids towards the Leukemia rat cell line, Vibrio fischeri and Scenedesmus vacuolatus based on molecular interaction potentials of ions.

In this study we present prediction models for estimating in silico the cationic hydrophobicity and the cytotoxicity (log [1/EC50]) of ionic liquids (ILs) towards the Leukemia rat cell line (IPC-81), the marine bacterium Vibrio fischeri and the limnic green algae Scenedesmus vacuolatus using linear free energy relationship (LFER) descriptors computed by COSMO calculations. The LFER descriptors used for the prediction model (i.e. excess molar refraction (E), dipolarity/polarizability (S), hydrogen-bonding acidity (A), hydrogen-bonding basicity (B) and McGowan volume (V)) were calculated using sub-descriptors (sig2, sig3, HBD3, HBA4, MR, and volume) derived from COSMO-RS, COSMO and OBPROP. With the combination of two solute descriptors (B, V) of the cation we were able to predict cationic hydrophobicity values (log ko ) with r (2) = 0.987 and standard error (SE) = 0.139 log units. By using the calculated log k o values, we were able to deduce a linear toxicity prediction model. In the second prediction study for the cytotoxicity of ILs, analysis of descriptor sensitivity helped us to determine that the McGowan volume (V) terms of the cation was the most important predictor of cytotoxicity and to simplify prediction models for cytotoxicity of ILs towards the IPC-81 (r (2) of 0.778, SE of 0.450 log units), Vibrio fischeri (r (2) of 0.762, SE of 0.529 log units) and Scenedesmus vacuolatus (r (2) of 0.776, SE of 0.825 log units). The robustness and predictivity of the two models for IPC-81 and Vibrio fischeri were checked by comparing the calculated SE and r (2) (coefficient of determination) values of the test set.

A stable fixed-dose combination tablet of pseudoephedrine and KOB extracts for the extended release.

Allergic rhinitis (AR) is characterized by inflammation of the nasal mucosa with hypersensitivity resulting from seasonal or perennial responses to specific environmental allergens and by symptoms like nasal rubbing, sneezing, rhinorrhea, lacrimation, nasal congestion and obstruction, and less frequently cough. KOB extracts, which is a polyherbal medicine consisting of 5 different herbs (Atractylodes macrocephala, Astragalus membranaceus, Saposhnikovia divaricata, Ostericum koreanum and Scutellaria baicalensis) had commonly been used for the treatment of various allergic diseases showed an anti-allergic effect by modulating mast cell-mediated allergic responses in allergic rhinitis, recently. On the other hand, pseudoephedrine is a sympathomimetic amine commonly used to relieve congestion in patients with allergic rhinitis and common colds. Considering the KOB's therapeutic mechanism, the combination with pseudoephedrine would be suitable for allergic rhinitis. This study is to obtain an effective extended release formulation using pseudoephedrine and KOB extracts to reduce side effects of drug due to repeated dosing and improve the compliance of patients for treatment of rhinitis and nasal decongestion. So, the fixed-dose combination tablet of pseudoephedrine and KOB extracts was prepared by direct compression and characterized by drug content, flowing characteristics and dissolution test. The drug content of baicalin of KOB extracts was within the range of 95-105% except for T1 formulation. The hardness and friability values of all formulations ranged from 9 to 13 kp and less than 1%, respectively. Taken together, T4 or T8 could be a stable fixed-dose combination tablet for extended release of pseudoephedrine and KOB extracts for nasal rhinitis.

Enhanced Controlled Transdermal Delivery of Ambroxol from the EVA Matrix.

To avoid the systemic adverse effects that might occur after oral administration, transdermal delivery of ambroxol was studied as a method for maintaining proper blood levels for an extended period. Release of ambroxol according to concentration and temperature was determined, and permeation of drug through rat skin was studied using two chamber-diffusion cells. The solubility according to PEG 400 volume fraction was highest at 40% PEG 400. The rate of drug release from the EVA matrix increased with increased temperature and drug loading doses. A linear relationship existed between the release rate and the square root of loading rate. The activation energy (Ea) was measured from the slope of the plot of log P versus 1000/T and was found to be 10.71, 10.39, 10.33 and 9.87 kcal/mol for 2, 3, 4 and 5% loading dose from the EVA matrix, respectively. To increase the permeation rate of ambroxol across rat skin from the EVA matrix, various penetration enhancers such as fatty acids (saturated, unsaturated), propylene glycols, glycerides, pyrrolidones, and non-ionic surfactants were used. The enhancing effects of the incorporated enhancers on the skin permeation of ambroxol were evaluated using Franz diffusion cells fitted with intact excised rat skin at 37° using 40% PEG 400 solution as a receptor medium. Among the enhancers used, polyoxyethylene-2-oleyl ether increased the permeation rate by 4.25-fold. In conclusion, EVA matrix containing plasticizer and permeation enhancer could be developed for enhanced transdermal delivery of ambroxol.

Cinnamon zeylanicum bark extract and powder mediated green synthesis of nano-crystalline silver particles and its bactericidal activity.

The exploitation of various plant materials for the biosynthesis of nanoparticles is considered a green technology as it does not involve any harmful chemicals. The present study reports the synthesis of silver (Ag) nanoparticles from silver precursor using the bark extract and powder of novel Cinnamon zeylanicum. Water-soluble organics present in the plant materials were mainly responsible for the reduction of silver ions to nano-sized Ag particles. TEM and XRD results confirmed the presence of nano-crystalline Ag particles. The pH played a major role in size control of the particles. Bark extract produced more Ag nanoparticles than the powder did, which was attributed to the large availability of the reducing agents in the extract. Zeta potential studies showed that the surface charge of the formed nanoparticles was highly negative. The EC(50) value of the synthesized nanoparticles against Escherichia coli BL-21 strain was 11+/-1.72 mg/L. Thus C. zeylanicum bark extract and powder are a good bio-resource/biomaterial for the synthesis of Ag nanoparticles with antimicrobial activity.

Glioblastoma cell death induced by asiatic acid.

Asiatic acid (AA), a triterpene, is known to be cytotoxic to several tumor cell lines. AA induces dose- and time-dependent cell death in U-87 MG human glioblastoma. This cell death occurs via both apoptosis and necrosis. The effect of AA may be cell type-specific as AA-induced cell death was mainly apoptotic in colon cancer RKO cells. AA-induced glioblastoma cell death is associated with decreased mitochondrial membrane potential, activation of caspase-9 and -3, and increased intracellular free Ca2+. Although treatment of glioblastoma cells with the caspase inhibitor zVAD-fmk completely abolished AA-induced caspase activation, it did not significantly block AA-induced cell death. AA-induced cell death was significantly prevented by an intracellular Ca2+ inhibitor, BAPTA/AM. Taken together, these results indicate that AA induces cell death by both apoptosis and necrosis, with Ca2+-mediated necrotic cell death predominating.

Physicochemical characterizations of piroxicam-poloxamer solid dispersion.

To develop an efficient topical delivery system for piroxicam using poloxamer gel formulation, physicochemical behavior of piroxicam in poloxamer was studied. The gelling property of poloxamer and the solubility of piroxicam in the poloxamer were investigated. The interaction between piroxicam and poloxamer was studied by x-ray diffractometry (XRD), infrared (IR) spectroscopy and differential thermal analysis (DTA) with a solid dispersion, coprecipitate, or physical mixture. Poloxamer 407 solutions showed the property of a gel when the concentration was higher than 15% (w/w) and poloxamer 407 increased the aqueous solubility of piroxicam by about 11-fold at the concentration of 22.5% (w/w). The results of XRD did not show the crystalline from of piroxicam in the solid dispersion and results of IR spectroscopic analysis showed an association between functional groups of piroxicam and poloxamer.

Enhancing effects of fatty acids on piroxicam permeation through rat skins.

To increase the skin permeation of piroxicam from the Poloxamer 407 gel, fatty acid was added as a penetration enhancer to the Poloxamer 407 gel containing 1% piroxicam. The enhancing effects of the enhancer on the skin permeation of piroxicam were evaluated using Franz diffusion cells fitted with intact excised rat skins. To elucidate the modes of the action of enhancers, thermal analysis and histological examinations were conducted. Among fatty acids tested, linoleic acid showed the highest enhancing effects, with an enhancement factor (EF) of 1.76. From the thermal analysis results, fatty acids have fluidizing effects on the stratum corneum. The skin pretreated with the Poloxamer 407 gels containing piroxicam including linoleic acid showed a loosely layered stratum corneum and wide intercellular space.

A polymer-supported proline-based diamine catalyst for the kinetic resolution of racemic secondary alcohols.

The preparation of polymer-supported proline-based diamine catalyst 12 for the kinetic resolution of racemic mixtures of secondary alcohols is described. Not only is the catalyst effective for the resolution of a host of different alcohols, it can also be recovered and reused several times without loss of either activity or selectivity. The catalyst has been used in conjunction with a polymer-supported sequestration strategy, giving rise to an essentially pure mixture of resolved products that can be separated using flash chromatography.

Permeation of piroxicam from the poloxamer gels.

Topical formulations of piroxicam were prepared using poloxamer 407 or poloxamer 188 by a cold method, and the permeation characteristics of piroxicam were evaluated. The permeation rate of piroxicam across the synthetic cellulose membrane and the rat skin decreased as the concentration of poloxamer increased. Though poloxamer gel exhibits reversed thermal behavior, the permeation rate of piroxicam increased with increasing temperature, indicating that the diffusional pathway of piroxicam is a water channel within the gel formulation. The pH of the gel did not affect the permeation rate of piroxicam significantly. As the concentration of piroxicam in the gel formulation increased, the permeation rate of piroxicam increased up to 1% and reached a plateau above 1%. Among various enhancers tested, polyoxyethylene-2-oleyl ether showed the highest enhancing effect, with an enhancement ratio of 2.84. Based on experimental results, the permeation rate of piroxicam can be controlled by changing the poloxamer concentration or drug concentration and by the addition of an appropriate enhancer.

Carrier-mediated uptake of rhodamine 123: implications on its use for MDR research.

We have examined the effects of verapamil and PSC 833 on cellular uptake and release of rhodamine 123 (R123) in two human cancer cell lines. Both verapamil and PSC 833 were able to increase R123 accumulation in the multidrug resistant (MDR) MV522/Q6 and KB-8-5 lines in the release study. However, the effects of these drugs on R123 accumulation during accumulation study were quite different. Incubation with PSC 833 increased R123 accumulation in both MDR lines. By contrast, incubation with verapamil only increased R123 accumulation in the KB-8-5 line. The failure of verapamil to increase R123 accumulation in the MV522/Q6 cells can be attributed to the presence of a carrier system in the parent MV522 cells that recognizes both R123 and verapamil, but not PSC 833, as substrates. These results imply that performing R123 accumulation study without first ascertaining possible role of a carrier system for cellular uptake of R123 and putative P-gp modulators might inadvertently lead one to draw improper conclusions on P-gp activity.