Diabetes-induced activation of protein kinase C inhibits store-operated Ca2+ uptake in rat retinal microvascular smooth muscle.

AIMS/HYPOTHESIS: To assess the effects of diabetes-induced activation of protein kinase C (PKC) on voltage-dependent and voltage-independent Ca2+ influx pathways in retinal microvascular smooth muscle cells. METHODS: Cytosolic Ca2+ was estimated in freshly isolated rat retinal arterioles from streptozotocin-induced diabetic and non-diabetic rats using fura-2 microfluorimetry. Voltage-dependent Ca2+ influx was tested by measuring rises in [Ca2+]i with KCl (100 mmol/l) and store-operated Ca2+ influx was assessed by depleting [Ca2+]i stores with Ca2+ free medium containing 5 micromol/l cyclopiazonic acid over 10 min and subsequently measuring the rate of rise in Ca2+ on adding 2 mmol/l or 10 mmol/l Ca2+ solution. RESULTS: Ca2+ entry through voltage-dependent L-type Ca2+ channels was unaffected by diabetes. In contrast, store-operated Ca2+ influx was attenuated. In microvessels from non-diabetic rats 20 mmol/l D-mannitol had no effect on store-operated Ca2+ influx. Diabetic rats injected daily with insulin had store-operated Ca2+ influx rates similar to non-diabetic control rats. The reduced Ca2+ entry in diabetic microvessels was reversed by 2-h exposure to 100 nmol/l staurosporine, a non-specific PKC antagonist and was mimicked in microvessels from non-diabetic rats by 10-min exposure to the PKC activator phorbol myristate acetate (100 nmol/l). The specific PKCbeta antagonist LY379196 (100 nmol/l) also reversed the poor Ca2+ influx although its action was less efficacious than staurosporine. CONCLUSION/INTERPRETATION: These results show that store-operated Ca2+ influx is inhibited in retinal arterioles from rats having sustained increased blood glucose and that PKCbeta seems to play a role in mediating this effect.

Design of asymmetrical RF and microwave bandpass filters by computer optimization

This paper presents an optimization-based approach to the design of asymmetrical filter structures having the maximum number of return- or insertion-loss ripples in the passband such as those based upon Chebyshev function prototypes. The proposed approach. has the following advantages over the general purpose optimization techniques adopted previously such as: less frequency sampling is required, optimization is carried out with respect to the Chebyshev (or minimax) criterion, the problem of local minima does not arise, and optimization is usually only required for the passband. When implemented around an accurate circuit simulation, the method can be used to include all the effects of discontinuities, junctions, fringing, etc. to reduce the amount of tuning required in the final filter. The design of asymmetrical ridged-waveguide bandpass filters is considered as an example. Measurements on a fabricated filter confirm the accuracy of the design procedure.

Understanding New Product Project Performance

Purpose – The purpose of this paper is to summarize the accumulated body of knowledge on the performance of new product projects and provide directions for further research. Design/methodology/approach – Using a refined classification of antecedents of new product project performance the research results are meta-analyzed in the literature in order to identify the strength and stability of predictor-performance relationships. Findings – The results reveal that 22 variables have a significant relationship with new product project performance, of which only 12 variables have a sizable relationship. In order of importance these factors are the degree of organizational interaction, R&D and marketing interface, general product development proficiency, product advantage, financial/business analysis, technical proficiency, management skill, marketing proficiency, market orientation, technology synergy, project manager competency and launch activities. Of the 34 variables 16 predictors show potential for moderator effects. Research limitations/implications – The validity of the results is constrained by publication bias and heterogeneity of performance measures, and directions for the presentation of data in future empirical publications are provided. Practical implications – This study helps new product project managers in understanding and managing the performance of new product development projects. Originality/value – This paper provides unique insights into the importance of predictors of new product performance at the project level. Furthermore, it identifies which predictor-performance relations are contingent on other factors.

Non-steroidal anti-inflammatory drug and aspirin use and the risk of head and neck cancer

Background: Evidence for non-steroidal anti-inflammatory drugs (NSAIDs) preventing head and neck cancer (HNC) is inconclusive; however, there is some suggestion that aspirin may exert a protective effect.

Methods: Using data from the United States National Cancer Institute Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, we examined the association between aspirin and ibuprofen use and HNC.

Results: Regular aspirin use was associated with a significant 22% reduction in HNC risk. No association was observed with regular ibuprofen use.

Conclusion: Aspirin may have potential as a chemopreventive agent for HNC, but further investigation is warranted.