Markedly enhanced intratumoral spread and antitumor effect of oncolytic adenovirus expressing decorin

With the aim of improving viral distribution and tumor penetration, we have engineered decorin expressing replication-incompetent (dl-LacZ-DCNG) and -competent (Ad-[DELTA]E1B-DCNG) adenoviruses. In both tumor spheroids and established solid tumors in vivo, administration of dl-LacZ-DCNG resulted in greater transduction efficiency and viral spread throughout the tumor mass. Ad-[DELTA]E1B-DCNG also enhanced viral distribution and tumor spread, leading to an increased anti-tumor effect and survival advantage. Upon histological analysis, Ad-[DELTA]E1B-DCNG also elicited greater percentage of apoptotic cells and extensive necrosis compared to those from untreated or control virus-treated tumors. Furthermore, Ad-[DELTA]E1B-DCNG substantially decreased extracellular matrix components within the tumor tissue, while normal tissue adjacent to the tumor was not affected. Finally, intratumoral administration of Ad-[DELTA]E1B-DCNG did not enhance but inhibited the formation of pulmonary metastases of B16BL6 melanoma cells in mice. Taken together, these data demonstrate the utility of decorin as a dispersion agent and suggest its utility and potential in improving the efficacy of replicating adenovirus-mediated cancer gene therapy

Factors Affecting the Perception of Importance and Practice of Patient Safety Management among Hospital Employees in Korea

SummaryPurposeThe study was undertaken to identify factors affecting perception of the importance and practice of patient safety management (PSM) among hospital employees in Korea.MethodsThis study was conducted using a descriptive design and a self-report questionnaire. Two hundred and eighty employees were recruited from three hospitals using a convenience sampling method. Measures were perception of the importance, practice, and characteristics of PSM. Data were analyzed using descriptive statistics including t test, one-way analysis of variance, Pearson's correlation analysis, and multiple regression.ResultsFactors affecting perception of the importance of PSM were whether hospital employees were in contact with patients while on duty, weekly working hours, education on PSM, and perceived adequacy of PSM system construction. Factors affecting the practice of PSM were perceived adequacy of work load, perceived adequacy of PSM system construction and perception of its importance.ConclusionThe findings of this study indicate a need for developing strategies to improve perception of the importance and practice of PSM among all hospital employees, and provide a reference for future experimental studies

Differential effect of corn oil-based low trans structured fat on the plasma and hepatic lipid profile in an atherogenic mouse model: comparison to hydrogenated trans fat

<p>Abstract</p> <p>Background</p> <p><it>Trans </it>fat are not desirable in many aspects on health maintenance. Low <it>trans </it>structured fats have been reported to be relatively more safe than <it>trans </it>fats.</p> <p>Methods</p> <p>We examined the effects of low <it>trans </it>structured fat from corn oil (LC), compared with high <it>trans </it>fat shortening, on cholesterol and fatty acid metabolism in apo E deficient mice which is an atherogenic animal model. The animals were fed a high <it>trans </it>fat (10% fat: commercial shortening (CS)) or a low <it>trans </it>fat (LC) diet for 12 weeks.</p> <p>Results</p> <p>LC decreased apo B and hepatic cholesterol and triglyceride concentration compared to the CS group but significantly increased plasma total cholesterol and triglyceride concentration and fecal lipids with a simultaneous increase in HDL-cholesterol level, apo A-I, and the ratio of HDL-cholesterol to total cholesterol (HTR). Reduction of hepatic lipid levels by inclusion of LC intake was observed alongside modulation of hepatic enzyme activities related to cholesterol esterification, fatty acid metabolism and fecal lipids level compared to the CS group. The differential effects of LC intake on the plasma and hepatic lipid profile seemed to be partly due to the fatty acid composition of LC which contains higher MUFA, PUFA and SFA content as well as lower content of <it>trans </it>fatty acids compared to CS.</p> <p>Conclusions</p> <p>We suggest that LC may exert a dual effect on plasma and hepatic lipid metabolism in an atherogenic animal model. Accordingly, LC, supplemented at 10% in diet, had an anti-atherogenic effect on these <it>apo E</it>^{<it>-/- </it>}mice, and increased fecal lipids, decreased hepatic steatosis, but elevated plasma lipids. Further studies are needed to verify the exact mode of action regarding the complex physiological changes and alteration in lipid metabolism caused by LC.</p

Opposing effects of protein kinase A and C on capacitative calcium entry into HL-60 promyelocytes.

Treatment of HL-60 cells with thapsigargin, a microsomal Ca2+/ATPase inhibitor, led to depletion of intracellular calcium stores followed by capacitative calcium entry. Stimulation of adenylyl cyclase with forskolin enhanced thapsigargin-induced Ca2+ influx. The forskolin effect was confirmed by enhanced fluorescence quenching induced by Mn2+ entry into fura-2 loaded cells. 1,9-Dideoxy-forskolin, an inactive analog of forskolin, did not affect capacitative calcium entry. On the other hand, phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C, inhibited thapsigargin-induced Ca2+ entry. Histamine and prostaglandin E2 (PGE2) elevated intracellular adenosine 3′:5′-cyclic monophosphate (cAMP) levels and enhanced the thapsigargin-induced capacitative calcium entry. Incubation with N-[2-(p-bromocynnamylamino)ethyl]-5-isoquinolinesulfonamide (H89), an inhibitor of protein kinase A (PKA), blocked the forskolin effect, and GF109203X, an inhibitor of protein kinase C (PKC), blocked the phorbol 12-myristate 13-acetate effect. The results suggest that protein kinase A regulates capacitative calcium entry positively, but that protein kinase C regulates Ca2+ influx negatively. Furthermore, after differentiation of HL-60 promyelocytes with dimethylsulfoxide to granulocytes, the inhibitory effect of phorbol 12-myristate 13-acetate became more pronounced, whereas the stimulatory effect of prostaglandin E2 did not change. This result suggests that the regulation of capacitative calcium entry by protein kinase C and protein kinase A develops differently during differentiation

Preventive effect of Ligularia fischeri on inhibition of nitric oxide in lipopolysaccharide-stimulated RAW 264.7 macrophages depending on cooking method

BACKGROUND: Ligularia fischeri (common name Gomchwi) is known for its pharmaceutical properties and used in the treatment of jaundice, scarlet-fever, rheumatoidal arthritis, and hepatic diseases; however, little is known about its anti-inflammatory effect. In this study the influence of blanching and pan-frying on the anti-inflammatory activity of Ligularia fischeri (LF) was evaluated. RESULTS: Fresh LF and cooked LF showed no significant effect on the viability of macrophages after 24 h incubation. Fresh LF was found to be the most potent inhibitor of nitric oxide (NO) production at 100 μg/ml, while pan-fried LF showed little inhibitory effect on lipoloysaccharide (LPS) stimulated murine machrophage RAW264.7 cells. In contrast with its effect on NO production, pan-fried LF showed significant attenuation of the expression of inducible nitiric oxide synthase (iNOS) compared with fresh LF. In the cooking method of LF, PGE2 production was not affected in the LPS-induced RAW 264.7 cells. In LPS-induced RAW 264.7 cells, pretreatment by fresh and cooked LF increased COX2 mRNA expression. The 3-O-caffeoylquinic acid content of blanching and pan-frying LF increased by 4.92 and 9.7 fold with blanching and pan-frying respectively in comparison with uncooked LF. CONCLUSIONS: Regardless of the cooking method, Ligularia fischeri exhibited potent inhibition of NO production through expression of iNOS in LPS-induced RAW264.7 cells

Chrysymenia wrightii (Rhodymeniales, Rhodophyta) - a new non-native species for the European Atlantic Coast

Chrysymenia wrightii, originally described from Japan, was found for the first time from the European Atlantic coast. It was collected in several subtidal rocky bottom habitats (9-14 meters depth) of the Ría de Arousa (Galicia, NW Spain). In this work, a description of Galician gametophytic and tetrasporophytic plants is provided. They are similar to the Mediterranean and Japanese plants. DNA sequence data of materials from Galicia and Korea were investigated using nuclear SSU and ITS1-5.8S-ITS2 rDNA and plastid rbcL sequences. No genetic variation was observed in the SSU, and only one substitution was detected in ITS and rbcL data between Galician and Korean samples, respectively. Our molecular data indicate that the Galician populations of C. wrightii are probably due to a recent introduction event from the northwest Pacific. Despite the fact that C. wrightii was formerly recorded as a new non-native species from a Mediterranean hotspot (Thau Lagoon, 1987-1989), it was never reported for the European Atlantic coast. After 30 years of its first report in the Mediterranean Sea, the simultaneous occurrence of C. wrightii in four subtidal localities of NW Spain suggests that this species may have colonized the region unnoticed for several years which may be related to its subtidal habitat and short life cycle. Similarly to the Mediterranean Sea, the introduction of C. wrightii on the European Atlantic coasts could be enhanced by the intensive aquaculture widely spread along the Galician coast. Curiously, C. wrightii is apparently restricted to both areas, the Ría de Arousa and the Thau Lagoon. In addition, many non-native species markedly represented in Galicia since the 1980’s were firstly reported in the Ría de Arousa. Consequently, the Ría de Arousa should be considered an outstanding European Atlantic hotspot of introduced marine species similar to the Solent region (South of England) or the Thau Lagoon.Xunta de Galicia (PGIDIT03PXIB10301PR) Ministerio de Educación y Ciencia, FEDER (CGL2006-03576/BOS) Korea Science and Engineering Foundation (R01-2006-000-10312-0) Basic Research Program of the Korea Polar Research Institute (PE08060)S