Non-invasive short-term assessment of retinoids effects on human skin in vivo using multiphoton microscopy.

BACKGROUND: The occlusive patch test developed for assessing topical retinoids activity in human skin has been extended as a short-term screening protocol for anti-ageing agents. In this model, biopsies are performed at the end of the occlusion period for morphological and immuno-histochemistry analysis. Multiphoton microscopy is a recent non-invasive imaging technique that combined with image processing tools allows the in vivo quantification of human skin modifications. OBJECTIVE: To validate with gold standards of anti-ageing that are retinoids, the relevance of multiphoton microscopy for kinetic and quantitative assessment in this model. METHODS: Twenty women, aged 50-65 years, were enrolled. Retinol 0.3% (RO) and Retinoic acid 0.025% (RA) were applied to the dorsal photo-damaged side of their forearm under occlusive patches for 12 days. A patch alone was applied to a third area as control. Evaluation was performed at day D0, D12 (end of treatment), D18 and D32 using multiphoton microscopy. Epidermal thickness, normalized area of the dermal-epidermal junction (DEJ) and melanin density were estimated using 3D image processing tools. RESULTS: Main significant results are: Epidermal thickening at D12, D18 and D32 with RO and at D12, D18 with RA vs. baseline and vs. CONTROL: Increased DEJ undulation at D32 with RO and at D12 with RA vs. baseline and vs. CONTROL: Decreased melanin content with RO (at D12 and D18 vs. baseline and at D32 vs. baseline and vs. control) and with RA (at D12 vs. baseline). CONCLUSIONS: This study shows that multiphoton microscopy associated to specific 3D image processing tools allows cutaneous effects induced by topical retinoids in this in vivo model to be non-invasively detected, quantified and followed over time. This innovative approach could be applied to the evaluation of other active compounds.

Enhanced killing of androgen-independent prostate cancer cells using inositol hexakisphosphate in combination with proteasome inhibitors.

Effective treatments for androgen-independent prostate cancer (AIPCa) are lacking. To address this, emerging therapeutics such as proteasome inhibitors are currently undergoing clinical trials. Inositol hexakisphosphate (IP6) is an orally non-toxic phytochemical that exhibits antitumour activity against several types of cancer including PCa. We have previously shown that treatment of PC3 cells with IP6 induces the transcription of a subset of nuclear factor-kappaB (NF-kappaB)-responsive and pro-apoptotic BCL-2 family genes. In this study, we report that although NF-kappaB subunits p50/p65 translocate to the nucleus of PC3 cells in response to IP6, inhibition of NF-kappaB-mediated transcription using non-degradable inhibitor of kappaB (IkappaB)-alpha does not modulate IP6 sensitivity. Treatment with IP6 also leads to increased protein levels of PUMA, BIK/NBK and NOXA between 4 and 8 h of treatment and decreased levels of MCL-1 and BCL-2 after 24 h. Although blocking transcription using actinomycin D does not modulate PC3 cell sensitivity to IP6, inhibition of protein translation using cycloheximide has a significant protective effect. In contrast, blocking proteasome-mediated protein degradation using MG-132 significantly enhances the ability of IP6 to reduce cellular metabolic activity in both PC3 and DU145 AIPCa cell lines. This effect of combined treatment on mitochondrial depolarisation is particularly striking and is also reproduced by another proteasome inhibitor (ALLN). The enhanced effect of combined MG132/IP6 treatment is almost completely inhibited by cycloheximide and correlates with changes in BCL-2 family protein levels. Altogether these results suggest a role for BCL-2 family proteins in mediating the combined effect of IP6 and proteasome inhibitors and warrant further pre-clinical studies for the treatment of AIPCa.

Procaspase-2S inhibits procaspase-3 processing and activation, preventing ROCK-1-mediated apoptotic blebbing and body formation in human B lymphoma Namalwa cells.

Procaspase-2S has been reported to selectively prevent membrane blebbing and apoptotic body formation in human monocytic-like leukemic U937 cells after etoposide (VP-16) treatment (Droin et al., Oncogene 20. 260-269, 2001). Here, we show that procaspase-2S overexpressed in human B lymphoma Namalwa cells inhibits procaspase-3 processing and activation, preventing cleavage and activation of Rho GTPase-associated ROCK-1 kinase. Failure of ROCK-1 activation in Namalwa cells correlates with a sustained delay in the appearance of membrane blebbing and apoptotic body formation after VP-16 treatment. Reciprocal coimmunoprecipitation experiments indicate that procaspase-2S binds to procaspase-3, but not procaspase-2L and -9 in untreated and VP-16-treated Namalwa cells. These data suggest that procaspase-2S-mediated anti-apoptotic effects are associated with inhibition of the processing and activation of procaspase-3 in VP-16-treated cells.

A randomized, controlled trial of vicarious experience through peer support for male first-time cardiac surgery patients: impact on anxiety, self-efficacy expectation, and self-reported activity.

OBJECTIVES: The purpose of this study was to determine whether vicarious experience, in which former patients exemplify the active lives they are leading, reduces anxiety and increases self-efficacy expectation and self-reported activity in patients after cardiac surgery. DESIGN: A randomized, controlled trial was used to evaluate an intervention that linked volunteers who had recovered from cardiac surgery in dyadic support with patients about to undergo similar surgery. The linking was achieved by means of visits during the hospitalization and recovery period. SUBJECTS: Fifty-six first-time male patients undergoing coronary artery bypass graft (CABG) surgery, with a mean age of 56.5 years, were randomly assigned to an experimental (n = 27) or control group (n = 29). OUTCOME MEASURES: Anxiety was measured at 48 hours and 24 hours before surgery, and again at 5 days and 4 weeks after surgery. Self-efficacy expectation and self-reported activity were both evaluated at 5 days and 4 weeks after surgery. RESULTS: Only the experimental group showed a significant decrease in anxiety during hospitalization. At all measurement times after the first intervention, the experimental group reported significantly lower levels of anxiety compared with the control group. The experimental group reported significantly higher levels of self-efficacy expectation and self-reported activity for general activities, walking, and climbing stairs evaluated at 5 days, and for general activities at 4 weeks after surgery. CONCLUSIONS: Vicarious experience provided through dyadic support is effective in helping patients undergoing cardiac surgery cope with surgical anxiety and in improving self-efficacy expectations and self-reported activity after surgery. Dyadic support is a valuable tool for recovery from cardiac surgery that needs to be maintained and explored through nursing practice and research.

[Use of research in clinical practice: support program for cardiac patients]. / L'utilisation de la recherche dans la pratique clinique: programme de parrainage à l'intention de patients cardiaques.

The research aims at the acquisition of knowledge and its application in the practice. The knowledge which most interests the nurses is the one pertaining to the improvement of nursing practice. Before initiating a change in the clinical practice on the basis of the research results, it is important to consider some rigorous criteria which will provide guidance to an enlightened decision as to whether such results should be adopted or not. With the help of an example of nursing care concerning a support programme for the benefit of heart patients, this article presents the application of a model of use of research results. The model consists of six phases in support of a critical judgement on the value of a scientific work: preparation, validation, comparative evaluation, decision making, adoption/application and evaluation. Each of these phases states the application of the model criteria, not only to the results, but to the whole research processes followed by the author. This model of research use can provide the nurse with means of proposing changes in the practice, based on the knowledge issuing from research.

[Social support intervention by former model patients for persons undergoing heart surgery]. / Intervention de soutien par des anciens patients modèles auprès de personnes devant subir une chirurgie cardiaque.

The objectives of this study were to determine whether vicarious experiences, in which expatients exemplify the active lives they are leading, can strengthen the belief in the restorability of cardiac functions. An experimental research design was used to evaluate an intervention designed to link volunteers who have successfully recovered from cardiac surgery in dyadic support with those individuals about to undergo similar surgery, by means of visits during the hospitalisation and recovery period. The intervention was intended to reduce anxiety and increase self-efficacy and activity performance. Through a randomised trial, 55 bypass surgery patients, aged 40-69 years, were allocated to either the experimental intervention (n = 27) or usual care (n = 28). The anxiety level was measured with the SPIELBERGER, GORSUCH and LUSHENE (1970) scale; self-efficacy and activity performance were measured with JENKIN's scales (1989). Data analysis with independent t tests revealed significant (p < 0.05) differences between groups in the anxiety level at 24 hours before surgery, and at 5 days and 4 weeks after surgery. Only the experimental group showed a significant (p < 0.02) decrease in anxiety during hospitalisation. Repeated analysis of variance showed significant (p < 0.05) differences between groups in perceived self-efficacy and performance of activities at 5 days and at 4 weeks after surgery. These results indicate that dyadic social support that volunteers offer cardiac surgery patients seems to be effective in helping the latter deal with cardiac events. Implications and recommendations for nursing practice and research were generated.

Color-flow duplex-directed manual occlusion of femoral false aneurysms.

PURPOSE: During the past 14 months we conducted a prospective clinical trial to evaluate the efficacy of duplex-directed manual occlusion (DDMO) of iatrogenic femoral false aneurysms (FFAs) as an alternative to standard operative management. METHODS: In all cases DDMO was performed with real-time color-flow imaging while steady, continuous external pressure was applied manually to the neck of the FFA by an experienced vascular technologist for a period of 10 minutes. RESULTS: Ten of the 11 FFAs treated with DDMO in this series were thrombosed successfully, requiring a mean of 30 minutes of compression per aneurysm (three compressions of 10 minutes each). DDMO was unsuccessful in one patient, whose session was terminated because of severe discomfort as a result of the procedure. All 10 patients with successfully thrombosed FFAs are without recurrence at 1-month follow-up color-flow duplex examination, and there has been no morbidity attributable to DDMO. CONCLUSIONS: We conclude that DDMO of postcatheterization FFA can be performed safely and is an inexpensive, effective, nonoperative method of managing such lesions. The precise role of this technique would appear to be as a first-line treatment for uncomplicated iatrogenic FFAs.

Adherence of Bordetella bronchiseptica and Pasteurella multocida to porcine nasal and tracheal epithelial cells.

The ability of 19 different Bordetella bronchiseptica isolates and 25 Pasteurella multocida isolates to adhere in vitro to porcine nasal and tracheal epithelial cells was examined. It was found that B. bronchiseptica adhered well to upper respiratory tract cells. In contrast the number of P. multocida organisms which adhered was four to six times less than the number of B. bronchiseptica adherent organisms. This difference was statistically significant (p less than 0.0001). Both microorganisms adhered in greater numbers to nasal cells than to tracheal cells (p less than 0.005). The data indicated that B. bronchiseptica possesses a greater ability than P. multocida to attach to porcine upper respiratory tract cells.