Anti-cell adhesive effect of phenylacetylshikonin analogues related to their cytotoxicity in A549 cells

An attempt to estabilish the relationship between anti-cell adhesive action of phenylacetylshikonin anallogues and their cytotoxicity against A549 cells was done. In the one hour incubation with A549 cells, alpha-methoxyphenylacetyl-(9), alpha-acetoxyphenylacetyl-(13), 3,4-methylen-edioxyphenylacetyl-(15) and 4-(N,N-dimethylamino)-phenylacetylshikonin (17) analogues showed a high anti-cell adhesive activity (IC(100) value, 4-8 mug/ml), while halophenylacetyl-and dimethoxy-or trimethoxyphenylacetyl analogues expressed no activity at 40 mug/ml, indicating that the presence of a bulky group at C'-alpha and a polar group at C-4 of phenylacetyl moiety may be important. A similar structure activity relationship exists for the 48 hr cytotoxocity (ED(50)) of phenylacetylshikonin analogues in A 549 cells, but not in either K562 or L1210 cells. Furthermore, the difference between IC(100) values for anti-cell adhesive activity and ED(50) values for cytotoxicity of potent compound in A549 cells was not so great (1.5 to 3 times). Based on these observations, it is proposed that the anti-cell adhesive action of phenylacetylshikonins might be responsible for their cytotoxicity in A549 cells.     

Interspecies variability and drug interactions of loxapine metabolism in liver microsomes.

Loxapine is a dibenzoxazepine neuroleptic that is metabolized by the liver in humans. In the present study, we investigated first in vitro loxapine metabolism in liver microsomes from various species including rats, mice, guinea pigs, dogs, rabbits, monkeys and humans. This enables us to choose between species to further validate drug-drug interaction studies. We observed the formation of desmethyl- and hydroxy- metabolites of loxapine after incubation of the different species liver microsomes. Hydroxylation pathway was major in all species. Wide interspecies variability of loxapine metabolism was observed. Loxapine metabolism was similar in human, guinea pig and dog microsomes. We screened in vitro effects of 67 molecules, representative of 8 therapeutic classes, on loxapine metabolism. Loxapine (100 microM) was incubated with guinea pig liver microsomes (1 mg/ml) 30 min at 37 degrees C with and without the presence of interacting drug. We found that most of psychotropics (alimemazine, cyamemazine and levomepromazine), antifungal (ketoconazole), anticancer drugs (daunorubicin, pirarubicin) and analgesic (nefopam) inhibited more than 50% of hydroxyloxapine formation in vitro. Complementary clinical and pharmacokinetic studies should be performed to confirm these results.     

Liquid-Crystal-Enabled Active Plasmonics: A Review

Liquid crystals are a promising candidate for development of active plasmonics due to their large birefringence, low driving threshold, and versatile driving methods. We review recent progress on the interdisciplinary research field of liquid crystal based plasmonics. The research scope of this field is to build the next generation of reconfigurable plasmonic devices by combining liquid crystals with plasmonic nanostructures. Various active plasmonic devices, such as switches, modulators, color filters, absorbers, have been demonstrated. This review is structured to cover active plasmonic devices from two aspects: functionalities and driven methods. We hope this review would provide basic knowledge for a new researcher to get familiar with the field, and serve as a reference for experienced researchers to keep up the current research trends.     

The development and psychometric evaluation of the Clinicians' Attitudes towards Responding and Escalating care of Deteriorating patients scale

BackgroundValidated measures of ward nurses' safety cultures in relation to escalations of care in deteriorating patients are lacking.ObjectivesThis study aimed to develop and evaluate the psychometric properties of the Clinicians' Attitudes towards Responding and Escalating care of Deteriorating patients (CARED) scale for use among ward nurses.MethodsThe study was conducted in two phases: scale development and psychometric evaluation. The scale items were developed based on a systematic literature review, informant interviews, and expert reviews (n = 15). The reliability and validity of the scale were examined by administering the scale to 617 registered nurses with retest evaluations (n = 60). The factor structure of the CARED scale was examined in a split-half analysis with exploratory and confirmatory factor analyses. The internal consistency, test–retest reliability, convergent validity, and known-group validity of the scale were also analysed.ResultsA high overall content validity index of 0.95 was obtained from the validations of 15 international experts from seven countries. A three-factor solution was identified from the final 22 items: ‘beliefs about rapid response system’, ‘fears about escalating care’, and ‘perceived confidence in responding to deteriorating patients’. The internal consistency reliability of the scale was supported with a good Cronbach's alpha value of 0.86 and a Spearman-Brown split-half coefficient of 0.87. An excellent test–retest reliability was demonstrated, with an intraclass correlation coefficient of 0.92. The convergent validity of the scale was supported with an existing validated scale. The CARED scale also demonstrated abilities to discriminate differences among the sample characteristics.ConclusionsThe final 22-item CARED scale was tested to be a reliable and valid scale in the Singaporean setting. The scale may be used in other settings to review hospitals' rapid response systems and to identify strategies to support ward nurses in the process of escalating care in deteriorating ward patients.