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Transference of recombinant VE-cadherin cytoplasmic domain alters endothelial junctional integrity and porcine microvascular permeability.

VE-cadherin constitutes endothelial adherens junctions through a homophilic binding of its extracellular domain and by the anchoring of its intracellular domain to actin cytoskeleton via catenins. The aim of this study was to determine the functional importance of VE-cadherin-cytoskeleton association in the maintenance of endothelial junctional integrity. A recombinant VE-cadherin cytoplasmic domain (rVE-cad CPD) was expressed in E. coli and purified through Ni-NTA spin columns. Immunoprecipitation assays showed that rVE-cad CPD was able to bind beta-catenin in vitro and to compete with endogenous VE-cadherin for binding of beta-catenin in human umbilical vein endothelial cells. A significant increase in the transendothelial flux of albumin was observed in the endothelial cell monolayers transfected with rVE-cad CPD. Importantly, transfection of rVE-cad CPD into intact isolated coronary venules markedly elevated the albumin permeability of the venular endothelium. In addition, immunofluorescence microscopic analysis revealed a conformational change of VE-cadherin from a uniform, continuous distribution along the cell membrane under control conditions to a diffuse, stitch-like pattern after rVE-cad CPD transfection. The effects were likely due to an attenuated anchorage of endogenous VE-cadherin to the cytoskeleton, as evidenced by a decreased partitioning of VE-cadherin in the detergent-insoluble cytoskeletal pool. The results suggest that the intracellular association of VE-cadherin with beta-catenin-linked cytoskeleton is essential to the maintenance of endothelial junctional integrity and microvascular permeability.

Animals↗

NAD(P)H:quinone oxidoreductase-1-dependent and -independent cytotoxicity of potent quinone Cdc25 phosphatase inhibitors.

Cdc25 dual-specificity phosphatases coordinate cell cycle progression and cellular signaling. Consequently, Cdc25 inhibitors represent potential anticancer agents. We evaluated >10,000 compounds for inhibition of human Cdc25 phosphatases and identified many potent and selective inhibitors, which all contained a quinone. Bioreductive enzymes frequently detoxify or activate quinones. Therefore, we evaluated the effect of NAD(P)H:quinone oxidoreductase-1 (NQO1) and reductase-rich microsomes on the activity of three quinone-containing Cdc25 inhibitors: 2-(2-hydroxyethylsulfanyl)-3-methyl-1,4-naphthoquinone (Cpd 5, compound 5; NSC 672121), 2,3-bis-(2-hydroxyethylsulfanyl)-1,4-naphthoquinone (NSC 95397), and 6-chloro-7-(2-morpholin-4-yl-ethylamino)quinoline-5,8-dione (NSC 663284). Each inhibitor was reduced by human NQO1 (K(m) of 0.3-0.5 microM) but none by microsomes. Compounds were evaluated with six cancer cell lines containing different amounts of NQO1: HT-29 (1056 nmol/mg/min), HCT116 (660 nmol/mg/min), sublines HCT116-R30A (28 nmol/mg/min) and HCT-116R30A/NQ5 (934 nmol/mg/min), MDA-MB-231/Q2 (null NQO1), and subline MDA-MB-231/Q6 (124 nmol/mg/min) but containing similar amounts of microsomal cytochrome P450 reductase and cytochrome b(5) reductase. Growth inhibition and G2/M arrest by Cpd 5 was proportional to NQO1 levels, requiring 4- to 5-fold more Cpd 5 to inhibit HCT-116 or HCT-116R30A/NQ5 compared with HCT-116R30A. In contrast, in all tested cell lines irrespective of NQO1 level, growth inhibition and G2/M arrest by NSC 95375 and NSC 663284 were similar (average IC(50) of 1.3 +/- 0.3 and 2.6 +/- 0.4 microM, respectively). NSC 95375 and NSC 663284 also caused similar Cdk1 hyperphosphorylation, indicating similar Cdc25 inhibition. However, lower Cpd 5 concentrations were needed to produce Cdk1 hyperphosphorylation in sublines with minimal NQO1. Thus, NQO1 detoxified Cpd 5, probably by reducing it to a less active hydroquinone, whereas NSC 95397- and NSC 663284-generated cytotoxicity was unaffected by NQO1.

CDC2 Protein Kinase↗

Cyclic AMP phosphodiesterase in Salmonella typhimurium: characteristics and physiological function.

The physiological function of cyclic AMP (cAMP) phosphodiesterase in Salmonella typhimurium was investigated with strains which were isogenic except for the cpd locus. In crude broken-cell extracts the properties of the enzyme were found to be similar to those reported for Escherichia coli. The specific activity in the mutant was less than 1% that in the wild type. Rates of cAMP production in the mutant were as much as twice those observed in the wild type. The amount of cAMP accumulated when cells grew overnight with limiting glucose was 4.5-fold greater in the mutant than in the wild type. The intracellular concentration of cAMP in the two strains was measured directly, using four different techniques to wash the cells to remove extracellular cAMP. The cAMP level in the cpd strain was only 25% greater than in the wild type. The functional concentration of the cAMP receptor protein-cAMP complex was estimated indirectly from the specific activity of beta-galactosidase in the two strains after introducing F'lac. When cells were grown with carbon sources permitting synthesis of different levels of cAMP, the specific activity of the enzyme was at most 25% greater in the cpd strain. The cpd strain was more sensitive to the effects of exogenous cAMP. Exogenous cAMP relieved both permanent and transient catabolite repression of the lac operon at lower concentrations in the cpd strain than in the wild type. When cells grew with glucose, glycerol, or ribose, exogenous cAMP inhibited growth of the mutant strain more than the wild type.

3',5'-Cyclic-AMP Phosphodiesterases↗

Occurrence and phenotypic characteristics of extended-spectrum beta-lactamases among members of the family Enterobacteriaceae at the Tel-Aviv Medical Center (Israel) and evaluation of diagnostic tests.

We assessed the prevalence and phenotypic characteristics of extended-spectrum beta-lactamase (ESBL) producers among cefuroxime-resistant (CXM-R) (MIC > or = 32 micro g/ml) members of the family Enterobacteriaceae in our institution. The 438 CXM-R clinical isolates obtained from nonurine sources among inpatients were screened. ESBL production was confirmed by disk diffusion assay using cefpodoxime (CPD), cefotaxime (CTX), and ceftazidime (CTZ) with and without clavulanate (CLAV). A difference of > or =5 mm in the size of the zone of inhibition in the presence of CLAV for at least one of the agents was considered representative of the ESBL phenotype: 186 isolates (42.5%) were confirmed as ESBL producers. The isolates tested and the rates of ESBL producers were as follows: Klebsiella spp. (n = 81), 79%; Proteus spp. (n = 58), 62%; Escherichia coli (n = 64), 53%; Enterobacter spp. (n = 69), 42%; Serratia spp. (n = 70), 14%; Citrobacter spp. (n = 25), 24%; Providencia spp. (n = 21), 24%; Morganella spp. (n = 41), 5%; and Kluyvera (n = 3), 0%. The overall sensitivity of isolated ESBL confirmatory tests was 79% for CPD-CLAV, 66% for CTZ-CLAV, and 91% for CTX-CLAV. Sensitivities of CTZ-CLAV confirmatory tests for Klebsiella spp., Proteus spp., E. coli, and Enterobacter spp. were 84, 22, 76, and 62%, respectively, and those for CTX-CLAV were 95, 97, 94, and 83%, respectively. They were 90% for CPD-CLAV and CTZ-CLAV, 95% for CPD-CLAV and CTX-CLAV, and 100% for CTZ-CLAV and CTX-CLAV. ESBL production was highly prevalent among Enterobacteriaceae. Using resistance to CXM as an ESBL screening criterion is a suitable option in high-incidence areas where Klebsiella spp. are not the dominant ESBL producers. This screening criterion may simplify the screening test and improve its sensitivity, although at the price of testing more isolates. The CTX-CLAV combination confirmed ESBL producers better than the CTZ-CLAV combination, with sensitivity varying between species. Combined CTZ-CLAV and CTX-CLAV testing detected all these strains; CPD-CLAV provided no additional benefit.

Anti-Bacterial Agents↗

Mentholated cigarettes and smoking habits in whites and blacks.

OBJECTIVE: To determine if cigarette mentholation is associated with the frequency of smoking and with quitting, and whether mentholation explains racial differences in these two smoking behaviours. DESIGN: Cross sectional analysis of case-control data on smoking and lung cancer. SUBJECTS: Limited to 19 545 current and former cigarette smokers. MAIN OUTCOME MEASURES: Smoking > 20 cigarettes per day (cpd) versus < or = 20 cpd, and continued smoking versus quit smoking. RESULTS: Among blacks, the prevalence odds ratio (POR) of heavy smoking (> or = 21 cpd) associated with mentholated cigarettes versus non-mentholated cigarettes was 0.7 (95% confidence interval (CI) 0.5 to 0.9) in current smokers and 0.6 (95% CI 0.4 to 0.9) in former smokers. Among whites, the corresponding POR were 0.9 (95% CI 0.8 to 1.0) and 0.9 (95% CI 0.8 to 1.0). Blacks were less likely to have been heavy smokers than whites, but the difference was unrelated to cigarette mentholation. The POR of continued smoking versus quitting, associated with mentholated cigarettes was 1.1 (95% CI 1.0 to 1.2) for both blacks and whites. CONCLUSION: Smoking > 20 cpd was independently associated with white race. Among blacks, smoking < or = 20 cpd was independently associated with mentholated cigarettes. The risk of quitting was not associated with cigarette menthol flavour.

Adult↗

Randomised trial investigating effect of a novel nicotine delivery device (Eclipse) and a nicotine oral inhaler on smoking behaviour, nicotine and carbon monoxide exposure, and motivation to quit.

OBJECTIVE: To monitor the effect of a novel nicotine delivery device that may produce fewer carcinogens (Eclipse) on cigarette smoking, carbon monoxide and nicotine concentrations, and motivation to give up smoking. The smoker's own brand of cigarette and a nicotine replacement product (Nicotrol inhaler) were used as comparisons. DESIGN: After baseline data were recorded, smokers were randomised to either Eclipse or inhaler for two weeks and then switched to the other product for another two weeks. Thereafter a second baseline was obtained. SETTING AND PARTICIPANTS: Fifty smokers were included and data are reported for the 40 with complete data sets. The smokers were not trying to quit but were interested in trying a new product to reduce their risk. They visited a smoking clinic 10 times during the six week period of the trial. INTERVENTION: No counselling to aid reduction by Eclipse or inhaler was given. MAIN OUTCOME MEASURES: At each visit smoking status and carbon monoxide concentrations were recorded. In half of the visits withdrawal symptoms, attitudes towards smoking, heart rate, and blood nicotine concentrations were also recorded. RESULTS: Eclipse use decreased the number of cigarettes smoked per day (cpd) from 19.1 cpd at baseline to 2.1 cpd (p < 0.001), but increased carbon monoxide concentrations in parts per million (ppm) from 21.0 ppm to 33.0 ppm (p < 0.001). A similar decrease in cigarettes smoked per day was seen with the Nicotrol inhaler, from 19.1 cpd to 4.8 cpd (p < 0.001), but carbon monoxide decreased from 21.0 ppm to 12.7 ppm (p < 0.001). The blood nicotine concentration remained fairly stable with Eclipse, increasing slightly from 16.8 ng/ml to 18.0 ng/ml, while for the inhaler a significant drop was noted, from 16.8 ng/ml to 12. 2 ng/ml (p < 0.002). Craving and withdrawal did not increase with Eclipse. Few significant adverse events occurred with Eclipse. CONCLUSIONS: Eclipse can dramatically decrease cigarette consumption without causing withdrawal symptoms or decreases in nicotine concentrations or motivation to quit altogether. Unlike the inhaler, Eclipse produces an increase in carbon monoxide concentration. Thus Eclipse may not be a safer cigarette.

Administration, Inhalation↗

Contrast sensitivity in patients with silicone intraocular lenses.

Contrast sensitivity in 64 patients aged from 50 to 69 years with an intraocular lens (IOL) was studied. There were 23 eyes with a silicone and 31 eyes with a polymethylmethacrylate (PMMA) IOL. Ten patients had a silicone IOL in one eye and a PMMA IOL in the other. Contrast sensitivity was examined with the Vistech far vision VCTS 6500 test. The contrast sensitivity test results in silicone and PMMA IOL eyes were in all cpd (cycles per degree) lines significantly worse than in normal eyes except in the 60-year-old group in the 18-cpd line. The contrast sensitivity test results were in all cpd lines better in the silicone IOL eyes than in the PMMA IOL eyes, but it reached significantly only in the 3-cpd line. In the 10 patients with the silicone lens in one and the PMMA lens in the other eye, the test results were also better in the silicone IOL eye; it also reached significance only in the 3-cpd line.

Aged↗

Backward masking is not required to elicit the central performance drop.

In some circumstances, texture discrimination performance peaks in the parafovea rather than at the fovea. Kehrer (1987) referred to this phenomenon as the central performance drop (CPD). In most studies showing the CPD, task performance has been limited by a backward mask. Morikawa (2000) has argued that in these studies the backward mask was critical to the emergence of the CPD. In three studies we use textures comprising left and right oblique line segments and limit performance by manipulating the orientation variability within the foreground and background textures. Using this method we demonstrate that significant CPDs emerge whether or not there is a backward mask. We conclude that in past studies of the CPD the backward mask functioned primarily as a source of spatial noise and that its temporal relation to the texture display is not critical to the emergence of the CPD.

Humans↗

Pathologic involvement of the left ventricle in chronic cor pulmonale.

To determine whether or not the left ventricle is pathologically involved in patients with chronic cor pulmonale, right and left ventricular weights, wall thickness, myocyte diameters, and percentage of fibrosis in 18 autopsied hearts were examined in patients with chronic pulmonary disease (CPD); ten had right ventricular hypertrophy on their electrocardiograms, and eight were without right ventricular hypertrophy. Five with extracardiopulmonary disease were used as controls. The weight of the right ventricle was significantly increased in CPD when compared to control subjects. Walls of both ventricles were significantly thicker in CPD. Myocyte diameters of both ventricles were significantly greater in CPD. The percentage of fibrosis in the right ventricle was significantly greater in CPD. The percentage of fibrosis in the left ventricle was significantly greater only in patients with right ventricular hypertrophy. We concluded that the left ventricle was also involved pathologically in patients with chronic cor pulmonale in the end stage of the disease.

Adult↗

Induction, distribution and repair of UV photodamage in the platyfish, Xiphophorus signum.

The genus Xiphophorus is an important model for investigating the etiology and genetics of sunlight-induced melanoma as well as other cancers. We used immunological techniques to determine the induction, distribution and repair of cyclobutane pyrimidine dimers (CPD) and pyrimidine(6-4)pyrimidone dimers ([6-4]PD) in different tissues of Xiphophorus signum exposed to ultraviolet-B light. We found that the (6-4)PD was induced at 5 to 10-fold lower frequency than the CPD and that scalation provided considerable photoprotection against both photoproducts. Photoenzymatic repair (PER) was very efficient in X. signum with most of the lesions removed within 20 min; PER of CPD occurred at about twice the rate of (6-4)PD. Nucleotide excision repair (NER) was much less efficient than PER and the rates of CPD and (6-4)PD removal were comparable. PER was more efficient in the caudal fin compared to the lateral epidermis; the opposite was true for NER. Although the initial rate of CPD excision was five-fold faster in the lateral epidermis compared to the caudal fin a considerable amount of residual damage remained in both tissues. The diverse photochemical and photobiological responses observed in X. signum suggest that heritable traits governing deoxyribonucleic acid damage induction and repair may be involved in the susceptibility of other Xiphophorus species to melanomagenesis.

Animals↗

Formation of cyclobutane pyrimidine dimers and 8-oxo-7,8-dihydro-2'-deoxyguanosine in mouse and organ-cultured human skin by irradiation with broadband or with narrowband UVB.

Narrowband UVB (NB-UVB) is a newly developed UVB source that, in addition to the previously used broadband UVB (BB-UVB), has been effectively used in phototherapy of various skin diseases. Besides its therapeutic effectiveness, NB-UVB also has some adverse effects that should be evaluated. As with all phototherapies, the photocarcinogenic potential of NB-UVB is the major concern. To assess the carcinogenic potential we measured the DNA damage induced by the two UVB sources because exposure of cells to UVB directly or indirectly induces DNA damage such as cyclobutane pyrimidine dimers (CPD) or 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo), respectively. These types of DNA damage cause mutations of oncogenes and tumor suppressor genes, which can lead to photocarcinogenesis. In the present study we measured the yield of CPD and the oxidative DNA damage marker, 8-oxodGuo, in organ-cultured human skin and in mouse skin after exposure to NB-UVB or BB-UVB at therapeutically equivalent doses. We show that a 10-fold higher dose of NB-UVB yields a similar amount of CPD compared with BB-UVB in two types of samples examined. In contrast to CPD, the formation of 8-oxodGuo after irradiation with NB-UVB at a 10-fold higher dose is 1.5-3 times higher than that caused by BB-UVB. These results suggest that although NB-UVB at equivalent erythema-edema doses is not more potent in inducing CPD formation than is BB-UVB, NB-UVB may generate a higher yield of oxidized DNA damage.

8-Hydroxy-2'-Deoxyguanosine↗

UVB dose-toxicity thresholds and steady-state DNA-photoproduct levels during chronic irradiation of inbred Xenopus laevis tadpoles.

Environmental stressors that severely impact some species more than others can alter ecosystems and threaten biodiversity. Genotoxic stress, such as solar UV-B irradiance, may induce levels of DNA damage at rates that exceed repair capacities in some species but remain below repair capacities in other species. Repair rates would seem to establish toxicity thresholds. We used inbred Xenopus laevis tadpoles in the laboratory to test the hypothesis that balances between rates of induction of cyclobutane pyrimidine dimers (CPDs; the major UV-B photoproduct in DNA) and rates of CPD removal (repair) can determine UV-B toxicity thresholds. As rates of chronic UV-B irradiance were progressively increased by decreased shielding of lamps, survival decreased sharply over a relatively narrow range of dose rates. Apparent toxicity thresholds were associated with large increases in steady-state CPD levels. Induction at twice the measured removal (repair) rate produced sustained high CPDs and 100% mortality. Induction at one-half the removal rate resulted in negligible CPD levels and low mortality. Increased intensity of visible radiation available to drive CPD photoreactivation, mimicking interspecies variation in DNA repair capacity, reduced steady-state CPD levels and increased survival at UV-B dose rates that were previously toxic, resulting in increased thresholds of apparent toxicity. We suggest that threshold effects due to DNA repair should generally be considered in assessments of effects of genotoxic agents on species-specific population decreases and human health risks.

Animals↗

Compensation as a risk factor for lung cancer in smokers who switch from nonfilter to filter cigarettes.

The likelihood of increasing the number of cigarettes per day (cpd), a common method of compensation, in smokers switching from nonfilter to filter cigarettes, was examined in newly diagnosed and histologically confirmed lung cancer cases including all cell types; 1,242 lung cancer cases and 2,300 sex and age matched hospital controls were interviewed in 20 hospitals from nine United States cities between 1969 and 1984. The mean increase in cpd for lung cancer cases was about twice that of controls. Using switchers who did not increase cpd as the referent group, there was a linear dose-response relationship between the odds of lung cancer and increasing level of compensation. The odds ratio increased from 1.19 to 2.37 in males and from 1.66 to 3.83 in females corresponding to increases of 1-10 to 21+ cpd after switching. Findings from this study suggest that increasing cpd after switching to filter cigarettes is an important risk factor for lung cancer that needs to be emphasized in epidemiologic studies. Proponents of the idea that switching cigarettes is of some benefit, should also advocate that individuals who continue smoking should avoid compensation after switching.

Adult↗

Surgical management of cricopharyngeal dysphagia in dogs: 14 cases (1989-2001).

OBJECTIVE: To determine outcome of and complications associated with cricopharyngeal myotomy or myectomy for treatment of cricopharyngeal dysphagia (CPD) in dogs. DESIGN: Retrospective study. ANIMALS: 14 dogs. PROCEDURE: Medical records of dogs with CPD that underwent cricopharyngeal myotomy or myectomy were examined. Follow-up information was obtained through telephone interviews with owners and referring veterinarians and clinical examinations when feasible. RESULTS: 16 surgical procedures were performed on the 14 dogs. Dysphagia was completely resolved immediately after surgery in 1 dog, and clinical signs did not recur (follow-up time of 8 years); a second dog also had immediate complete resolution of dysphagia, but follow-up time was only 10 days. Three dogs had transient complete resolution with a mean time to recurrence of dysphagia of 12.3 weeks (range, 2 to 36 weeks). Three dogs had permanent partial resolution. Six dogs had no improvement after surgery. Eight of the 14 dogs were euthanatized because of problems related to CPD, including persistent dysphagia (n = 8) and aspiration pneumonia (5). CONCLUSIONS AND CLINICAL RELEVANCE: The failure rate for dogs undergoing surgical treatment of CPD may be high, particularly if concurrent aspiration pneumonia or malnutrition is not addressed prior to surgery. For those dogs with concurrent diseases, more aggressive medical management, such as enteral tube feeding, may be warranted rather than surgery. In dogs with CPD complicated by other anatomic or functional conditions, such as myasthenia gravis, laryngeal paralysis, and esophageal stricture, surgery may also not be indicated.

Animals↗

Filterability and bank blood conservation media.

A study was made of storage lesions of packed red cells stored in different preservative media: CPD, CPD-adenine, CPD-SAG, and CPD-pentoxifylline. The following chemical and physical parameters were studied: filterability, viscosity, ATP, 2-3,DPG pH, osmotic fragility, scanning electron microscopy pattern, blood gas levels. Tests were performed on days 0, 2, 4, 8, 16 and 24. The number and intensity of storage lesions in vitro give an indication of changes in oxygen-delivery capacity and flow characteristics of erythrocytes over a period of storage at 4 degrees C in different preservative media. CPD was found to maintain pertinent RBC properties up to Day 15. Adding adenine made little difference, whereas adding SAG gave better results. Pentoxifylline did not show appreciable effects in the initial concentrations used, which were close to those employed in medical practice. A preservative mixture ensuring maintenance of normal blood values during storage at 4 degrees C has yet to be found. Continued study of pentoxifylline should be conducted using higher concentrations of this additive.

Adult↗

Performance of dairy cattle fed citrus pulp or corn products as sources of neutral detergent-soluble carbohydrates.

The effects of modifying the dietary profile of neutral detergent-soluble carbohydrates (NDSC) on milk production and rumen fermentation were determined. Corn silage and alfalfa hay-based diets were formulated to contain 40% calculated NDSC supplied primarily by dried citrus pulp as a source of neutral detergent-soluble fiber (NDSF), or corn products as sources of starch. Diets were compared within cow with reversal experiments with two periods. In experiment 1, 11 multiparous Holstein cows including three ruminally cannulated animals were individually fed diets containing 23.6% citrus pulp (diet CPD) or 25.3% corn hominy (diet HD) on a dry matter basis. In experiment 2, 184 animals fed as two groups received diets containing 20.5% citrus pulp (diet CPD) or 19.5% cornmeal (diet CMD). Diets CPD provided more dietary NDSF and HD and CMD more starch. In experiment 1, cows fed HD had a greater milk protein percentage (+0.12%), and tended to yield more milk protein (0.08 kg/d) than cows fed CPD. Although ruminal H+ concentrations did not differ between diets, diet x time postfeeding interactions were significant. Ruminal organic acid concentrations did not differ between diets. In experiment 2, cows fed CMD yielded more milk (3.9 kg/d), 3.5% fat- and protein-corrected milk (2.6 kg/d), fat (0.05 kg/d), and protein (0.08 kg/d), whereas cows fed CPD produced greater concentrations of fat (+0.18%), and milk urea nitrogen (0.76 mg/dl). Modifying the proportions of NDSC in the diet can alter milk production and composition, the pattern of ruminal fermentation, and N utilization in dairy cows.

Animal Feed↗

Nurses' perceptions of continuing professional development.

AIM: To investigate NHS and private sector nurses' perceptions of the value of continuing professional development (CPD), and to analyse the factors that influence these perceptions and any potential barriers to successful CPD. METHOD: Questionnaires were sent to 200 staff working in two NHS trusts and 13 nursing homes. Following analysis of the questionnaires, interviews took place with eight self-selecting respondents to explore certain issues further. Each interview was taped and lasted 30-45 minutes. The venue for the interview was arranged to suit the respondent, either in a private office in the work environment or at home. Written consent was sought before taping the interview. RESULTS: From the results of the postal questionnaires a largely positive perception of CPD was determined. However, it was shown that there were some barriers to professional development that have not previously been reported in the literature. Managers' leadership styles were found to influence nurses' perceptions of the value of CPD, as well as their ability to reflect, which affected the application of learning to practice. CONCLUSION: Influencing factors included managers' leadership styles and their responsiveness to change, as well as a reduced ability for nurses to reflect. A disassociation between post-registration education and practice (PREP) and CPD in terms of understanding the purpose of PREP was also discovered among nurses.

Attitude of Health Personnel↗

[Herbal compound 861 inhibits NF-kappa B binding activity of hepatic stellate cells in vitro].

OBJECTIVE: To investigate the effect of Cpd 861 on nuclear factor-kappa B (NF-kappa B) binding activity of hepatic stellate cells (HSC) in vitro. METHODS: The study was carried out on the culture of hepatic stellate cell line, 5mg/ml of Cpd 861 was added and incubated for 48 hours. NF-kappa B binding activity was evaluated by electrophoretic mobility shift assays. IL-6 and sICAM-1 levels in the cultured supernatant were detected by ELISA. Cell apoptosis was detected by flow cytometry and TUNEL. RESULTS: Cpd 861 suppressed the binding activity of NF-kappa B in HSCs compared with the control group. Moreover, IL-6 and sICAM-1 levels in the cultured supernatant were decreased (P<0.05) and apoptosis rate of HSCs was increased after Cpd 861 incubation (P<0.01). CONCLUSIONS: The inhibitory effect on NF-kappa B binding activity might be part of the cellular mechanism of Cpd 861 to treat liver fibrosis.

Animals↗