Permeation enhancement of a highly lipophilic drug using supersaturated systems

The potential of supersaturation as a method for enhancing the membrane permeation of highly lipophilic compounds has been investigated using, as a model system, the transport of a lavendustin derivative (LAP, log K(o/w) = 5) through silicone membrane. Propylene glycol-water mixtures, which permitted the formulation of LAP at different levels of saturation, were prepared and tested for stability prior to conducting membrane permeation studies. The transport of LAP across silicone membrane from donor solutions containing the drug at different degrees of saturation (DS = 1-5) was evaluated by two independent experimental methods: (i) using attenuated total-reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and (ii) using standard vertical diffusion cells followed by quantification with high-performance liquid chromatography (HPLC). Both methods demonstrated a linear relationship between the DS of the applied solution and the flux through the membrane, yielding similar values for the diffusion coefficients of LAP [diffusion cells, D = 1.75 ( +/- 0.16) x 10(-7) cm(2) s(-1) and ATR-FTIR, D = 1.42 ( +/- 0.26) x 10(-7) cm(2) s(-1)). In addition to the characterization of LAP permeation, ATR-FTIR spectroscopy enabled an examination of solvent transport across the membrane.     

Ethical dilemmas related to counseling clients living with HIV/AIDS

This study tested an eight-factor model of client actions/decisions in terms of the extent to which professionals counseling persons with HIV/AIDS believed that those actions/decisions presented ethical dilemmas, and the frequency with which they encountered such actions. A confirmatory factor analysis lent initial support for the hypothetical eight-factor ethical-dilemma model for the ratings regarding the extent to which the participants believed those items constituted ethical dilemmas. Similar results were obtained for the frequency ratings, but in this case a second, competing model was equally plausible. Several significant predictors of participant ratings were found and are discussed.     

Importance of delta opioid receptors in maintaining high alcohol drinking

We have previously reported that naloxone, a nonspecific opioid receptor antagonist, suppresses alcohol but not water consumption by male rats that have been genetically selected for high voluntary alcohol drinking. However, the identity of the specific opioid receptor subtype that may mediate alcohol drinking is not known. This paper reports that a selective delta opioid receptor antagonist is as effective as naloxone in suppressing alcohol consumption and that an enkephalinase inhibitor, which potentiates the action of endogenous enkephalins, increases alcohol intake. These results suggest that alcohol-induced activation of the endogenous enkephalinergic system, and occupation of delta opioid receptors, are involved in the maintenance of continued alcohol drinking.     

Do explicit appropriateness criteria enhance the diagnostic yield of colonoscopy?

BACKGROUND AND STUDY AIMS: Appropriateness of use of colonoscopy is an important issue in health care in the quest to improve quality of care while at the same time containing costs. This prospective study examined whether detailed and explicit appropriateness criteria significantly improve the diagnostic yield of colonoscopy. PATIENTS AND METHODS: Consecutive patients referred for diagnostic colonoscopy at five centers (one university hospital and its outpatient department, two district hospitals, and two gastroenterology practices) were prospectively studied over a 17-month period. The appropriateness of the indications for these colonoscopies was assessed using explicit Swiss criteria developed by the Rand Corporation/University of California at Los Angeles (RAND/UCLA) panel method, and the relationship between appropriateness of use and the presence of clinically relevant endoscopic lesions was analysed. RESULTS: 1188 patients were included in the study. Indications for 1144 (96.3 %) of the colonoscopies could be evaluated using explicit criteria; 64.1 % of the colonoscopies were judged appropriate, 13.3 % uncertain and 22.6 % inappropriate. Significant endoscopic lesions were found in 23.8 % of the colonoscopies. Colonoscopies judged appropriate or uncertain yielded significantly more relevant lesions than did those judged to be inappropriate (25.6 % vs. 17.4 %; P = 0.007). Of 51 colon cancers, all but one were found in colonoscopies judged to be appropriate or uncertain. In a multivariate analysis, the diagnostic yield of colonoscopy was significantly influenced by appropriateness, patient gender and treatment setting. CONCLUSIONS: The use of detailed and explicit appropriateness criteria for colonoscopy significantly enhances the identification of relevant lesions and in particular of colon cancer. The use of such criteria could therefore improve patient selection for colonoscopy and thus contribute to efforts aimed at enhancing the quality and efficiency of care.     

White matter integrity in polydrug users in relation to attachment and personality: a controlled diffusion tensor imaging study

The relationship between substance use disorders (SUD. In this study we compared two groups of PUD inpatients (abstinent: n = 18, in maintenance treatment: n = 15) to healthy controls (n = 16) with respect to neural connectivity in white matter, and their relation to behavioral parameters of personality factors/organization and attachment styles. Diffusion Tensor Imaging was used to investigate white matter structure. Compared with healthy controls, the PUD patients showed reduced fractional anisotropy (FA) and increased radial diffusivity (RD) mainly in the superior fasciculus longitudinalis and the superior corona radiata. These findings suggest diminished neural connectivity as a result of myelin pathology in PUD patients. In line with our assumptions, we observed FA in the biggest cluster as negatively correlated with anxious attachment (r = 0.36, p < 0.05), personality dysfunctioning (r = ?0.41; p < 0.01) as well positively correlated with personality factors Openness (r = 0.34; p < 0.05) and Agreeableness (r = 0.28; p < 0.05). Correspondingly these findings were inversely mirrored by RD. Further research employing enhanced samples and addressing longitudinally neuronal plastic effects of 相似文献