Enhancedex vivo buccal transport of propranolol: Evaluation of phospholipids as permeation enhancers
The aim of the present study was to evaluate the effects of two phospholipid permeation enhancers, lysophosphatidylcholine (LPC) and didecanoylphosphatidylcholine (DDPC), along with a fusidic acid derivative, sodium taurodihydrofusidate (STDHF) and ethanol (EtOH) on the buccal transport of propranolol hydrochloride (PPL) using anex vivo buccal diffusion model. The permeation rate of [3H]PPL as measured by steady-state fluxes increased with increasing EtOH concentration. A significant flux enhancement (P<0.05) was achieved by EtOH at 20 and 30 %v/v concentrations. At a 0.5 %w/v permeation enhancer concentration, the buccal permeation of [3H]PPL was significantly enhanced by all the enhancers studied (i.e., LPC, DDPC and STDHF) compared to the control (phosphate-buffered saline pH 7.4, PBS). LPC and DDPC displayed a greater degree of permeation enhancement compared with STDHF and EtOH-PBS mixtures with an enhancement ratio of 3.2 and 2.9 for LPC and DDPC, respectively compared with 2.0 and 1.5 for STDHF and EtOH:PBS 30:70 %v/v mixture, respectively. There was no significant difference between LPC and DDPC for the flux values and apparent permeability coefficients of [3H]PPL. These results suggest that phospholipids are suitable as permeation enhancers for the buccal delivery of drugs.

title: The effect of storage conditions on the permeability of porcine buccal mucosa
abstract: The impact of storage conditions on the permeability of porcine buccal mucosa to [3H]water and [14C]mannitol was assessed. The fresh porcine buccal tissue (fresh tissue) was obtained by utilizing pig heads within 24 hours of slaughter. The stored and frozen porcine buccal tissues (stored tissue and frozen tissue) were obtained after the storage of the tissue intact in the pig heads at 4 degrees C or -20 degrees C, respectively, for 24 h. The results demonstrated that the barrier properties of the porcine buccal mucosa were maintained with regard to [3H]water permeability when stored at 4 degrees C for 24 h. However, freezing the tissue resulted in tissue damage illustrated by a significant increase in [3H]water permeability. [14C]Mannitol does not appear to be a suitable model solute to assess the ex vivo permeability of porcine buccal mucosa due to its extremely low permeability.

title: Buccal permeation of [D-Ala(2), D-Leu(5)]enkephalin from liquid crystalline phases of glyceryl monooleate.
abstract: The ex vivo buccal permeability of a [D-Ala(2), D-Leu(5)]enkephalin (DADLE) and glyceryl monooleate (GMO) was examined from the cubic and lamellar liquid crystalline phases of GMO and aqueous phosphate-buffered saline (pH 7.4, PBS) solution across excised porcine buccal mucosa mounted in a Franz cell. GMO was released in vitro from the liquid crystalline phases indicating the erosion of the liquid crystal matrices. GMO released from the liquid crystalline matrices permeated the porcine buccal mucosa with fluxes of 0.10+/-0.03 and 0.07+/-0.00%/cm(2) per h for the cubic and lamellar phases, respectively. The flux of DADLE (1.21+/-0.32 and 1. 15+/-0.11%/cm(2) per h for the cubic and lamellar phases, respectively) from the liquid crystalline phases was significantly enhanced by the GMO compared with PBS solution (0.43+/-0.08%/cm(2) per h) during the initial permeation phase (t<3 h). Our results suggest that the cubic and lamellar liquid crystalline phases can be considered as promising buccal drug carriers for peptide drugs as well as acting as permeation enhancers.

title: CIP2A expression is associated with synovial hyperplasia and invasive function of fibroblast-like synoviocytes in rheumatoid arthritis
abstract: Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a recently identified oncoprotein that leads to cellular proliferation in cancer cells. We aim to investigate CIP2A expression in fibroblast-like synoviocytes (FLS) and its association with the histopathological grade of synovitis and the invasive function of FLS in rheumatoid arthritis (RA). CIP2A protein expression was measured in 8 RA FLS and 8 OA FLS using Western blot analysis. CIP2A mRNA expression from 19 RA FLS and 7 OA FLS was measured using real-time PCR. Synovitis score of RA FLS-matched synovial tissues was semiquantitatively measured by two independent pathologists. An in vitro cell invasion assay was performed using RA FLS treated with CIP2A small interfering RNA (siRNA) or with control vector. Western blot analysis showed that CIP2A is more frequently overexpressed in RA FLS compared with OA FLS. CIP2A mRNA expression was higher in RA FLS compared with those in OA FLS, but did not reach statistical significance (P = 0.076). In RA, total synovitis score was strongly correlated with FLS CIP2A mRNA expression (rs = 0.849, P = 0.043). TNF-α treatment induced a robust increase in the invasive function of control FLS (P = 0.0021), but no significant effect was observed in CIP2A siRNA-treated FLS. Our data demonstrate that CIP2A expression is closely associated with the histopathological score of synovitis and invasive function of FLS in RA. These results suggest that CIP2A may play a critical role in the destructive process in RA and warrant further investigation of CIP2A as a therapeutic target.

title: Microcantilever actuation via periodic internal heating.
abstract: This paper reports electrothermal actuation of silicon microcantilevers having integrated resistive heaters. Periodic electrical excitation induced periodic resistive heating in the cantilever, while the cantilever deflection was monitored with a photodetector. Excitation was either at the cantilever resonant frequency, f(0), f(0)/2, or f(0)/3. When the time averaged maximum cantilever temperature was 174 degrees C, the cantilever out-of-plane actuation amplitude was 484 nm near the cantilever resonance frequency of 24.9 kHz. This actuation was sufficiently large to operate the cantilever in intermittent contact mode and scan a calibration grating of height of 20 nm.

title: Korean version of the Revised Caregiving Appraisal Scale: a translation and validation study.
abstract: This paper is a report of a study to examine the reliability and validity of a Korean version of the Revised Caregiving Appraisal Scale with Korean caregivers of older stroke survivors.



The Revised Caregiving Appraisal Scale was developed in the United States of America for an American English-speaking population to measure primary caregivers' appraisals of potential stressors and the efficacy of their coping efforts related to caregiving experiences.



Using the back-translation method, the instrument was translated into Korean. The Korean version of the Revised Caregiving Appraisal Scale was self-administered by 147 primary family caregivers recruited from three outpatient clinics and two home health agencies in Korea. The study was conducted in 2005.



In this sample, Cronbach's alpha for the total scale was 0.86. Reliability coefficients for each of the five subscales ranged from 0.40 to 0.85. Two subscales, burden and satisfaction, showed good reliability; one subscale, impact, showed marginally acceptable reliability; two subscales, mastery and demand, had low reliability. Principal components factor analysis of the Korean version of the Revised Caregiving Appraisal Scale yielded six factors. Except for the mastery domain, which was divided into two factors, the other factors were similar to those in the original scale.



The Korean version of the Revised Caregiving Appraisal Scale had adequate reliability and validity in a sample of Korean caregivers of stroke survivors. It can be used to assess the impact of caregiving and interventions on Korean caregiver attitudes. Further studies are needed with different categories of caregiver.

title: Underexpression of TIM-3 and Blunted Galectin-9-Induced Apoptosis of CD4+ T Cells in Rheumatoid Arthritis
abstract: The aim of this study is to compare the expression of TIM-3 from CD4+ T cells from rheumatoid arthritis (RA) patients and healthy controls and to evaluate the effect of galectin-9 (Gal-9) on apoptosis of CD4+ T cells in these patients. CD4+ T cells from RA patients and healthy controls were isolated from peripheral blood mononuclear cells and were activated. The expression of TIM-3 mRNA in CD4+ T cells was measured using real-time polymerase chain reaction. CD4+ T cells were activated in the presence of graded doses of Gal-9 or control, and Gal-9-induced cytotoxicity and apoptotic activity of CD4+ T cells were analyzed using MTT assays and annexin-V staining, respectively. TIM-3 mRNA expression was significantly lower in CD4+ T cells from RA patients compared with those in healthy controls (p = 0.028). CD4+ T cell survival as measured by MTT assay when incubated with Gal-9 (15 nM) was significantly higher in RA patients than in healthy controls (p = 0.002). Apoptotic activity of CD4+ T cells from healthy controls as measured by annexin staining increased with graded doses of Gal-9 (0 nM vs. 30 nM, 0 nM vs. 90 nM, p = 0.016 each). However, apoptotic activity of CD4+ T cells from RA patients did not change despite the stimulation with Gal-9. Gal-9-mediated apoptosis of CD4+ T cells is dysfunctional in RA patients. Blunted Gal-9-mediated apoptosis may be exerted through underexpression of TIM-3 that negatively regulates Th1 response. Our data suggest that TIM-3 and its interaction with Gal-9 may play an important role in the pathogenesis of RA and may represent a potential therapeutic target.

title: Multidrug-resistant tuberculosis in a lung transplant recipient.
abstract: Tuberculosis infection has been a relatively rare complication after lung transplantation. However, as more countries in which Mycobacterium tuberculosis infection remains endemic embark on lung transplant programs, the occurrence of multidrug-resistant tuberculosis after transplantation is a genuine threat. We report the first case of multidrug-resistant tuberculosis in a double-lung transplant recipient who probably acquired the disease from the donor. We discuss the problems in clinical management of post-transplant tuberculosis infection and of drug-resistance.