Zinc-binding groups modulate selective inhibition of MMPs

The need for selective matrix metalloproteinase (MMP) inhibition is of interest because of the range of pathologies mediated by different MMP isoforms. The development of more selective MMP inhibitors (MMPi) may help to overcome some of the undesired side effects that have hindered the clinical success of these compounds. In an effort to devise new approaches to selective inhibitors, herein we describe several novel MMPi and show that their selectivity is dependent on the nature of the zinc-binding group (ZBG). This is in contrast to most current MMPi, which obtain isoform selectivity solely from the peptidomimetic backbone portion of the compound. In the present study, six different hydroxypyrone and hydroxypyridinone ZBGs were appended to a common biphenyl backbone and the inhibition efficiency of each inhibitor was determined in vitro (IC(50) values) against MMP-1, -2, -3, -7, -8, -9, -12, and -13. The results show that the selectivity profile of each inhibitor is different as a result of the various ZBGs. Computational modeling studies were used to explain some trends in the observed selectivity profiles. To assess the importance of the ZBG in a biological model, two of the semiselective, potent MMPi (and one control) were evaluated using an isolated perfused rat heart system. Hearts were subjected to ischemia reperfusion injury, and recovery of contractile function was examined. In this model, only one of the two MMPi showed significant and sustained heart recovery, demonstrating that the choice of ZBG can have a significant effect in a relevant pathophysiological endpoint.     

Effect of ageing and μ-calpain markers on meat quality from Brangus steers finished on pasture

Brangus steers (n = 247) finished on pasture were used to evaluate the effects of post-mortem ageing and polymorphism CAPN1 316 and CAPN1 4751 markers on meat tenderness and objective colour measurements (CIEL*a*b*) of m. Longissimus dorsi. Ageing meat for 7 days decreased shear force (SF) by 13.7% and improved a* (8.4%) and b* (10%) compared to ageing for 1 day. No difference between 7 and 14 days of ageing was found for SF, a* and b*. However, L* increased markedly with ageing. Fitting both markers simultaneously, CAPN1 316 showed association with SF and L* and CAPN1 4751 with a* and b*. Fitting the markers individually, CAPN1 4751 affected all traits and CAPN1 316 showed association with SF and L*. Post-mortem ageing and the use of markers represent two independent and alternative tools that could be used for improving quality of meat from Brangus cattle.     

Approaches to study interactions between small DNA viruses and differentiated tissue

Polyomavirus (Py) derives its name from the early observation of multiple tumors that develop in newborn mice following inoculation with this family of viruses. In nature, however, tumor development is rare in the virus life cycle, rather a two-phase infection occurs, acute and persistent, resulting in a final latent infection in the kidneys. The acute phase induces an antiviral immune response, although no recognizable inflammation, which can last the lifetime of the mouse, even passing on antibodies to its offspring. The structure, replication, and expression of the Py viral genome in permissive and nonpermissive infections has been studied extensively in various cell culture systems. However, the nature of Py expression, replication, and immunopathogenesis in mice has not been thoroughly researched.     

Ionic conductivity and spectroscopic characterisation of γ-LiAlO2-filled polymer electrolytes

Spectroscopic characterisation of γ-LiAlO₂ composite polymeric electrolytes based on poly-(ethylene oxide)(PEO)/perfluorinated polyphosphazene blends and LiPF₆ as electrolyte was studied by means of FTIR and X-ray spectroscopy. Ionic conductivity was analysed by using complex impedance. A parallel study was made on samples containing propylene carbonate as plasticizer instead of γ-LiAlO₂. The results obtained indicate, in a first approximation, that there is a drastic change in PEO morphology resulting from the co-ordination with the lithium salt and, at the same time, that the morphology of the composite polymer electrolytes is dependent on the nature of the polymer host. Complex impedance data show that the incorporation of γ-LiAlO₂ enhances the ionic conductivity of the composite polymer electrolyte, a reverse behaviour is found for the composite systems plasticized with PC.     

Morphological characterization of γ-LiAlO2-filled composite polymer electrolytes containing LiPF6

Morphological properties of composite polymer electrolytes based on blends of polyethylene oxide (PEO) and a perfluorinated polyphosphazene (PPz) containing LiPF₆ as lithium salt and a finely divided ceramic filler, γ-LiAlO₂, were studied by using polarizing optical microscopy and differential scanning calorimetry (DSC). A parallel study was performed on propylene carbonate plasticized composite polymer electrolytes. Results indicate that both the morphology and the thermal properties depend upon the composition of the polymer host, a result not observed in composite polymer electrolytes having the same polymer composition containing LiCF₃SO₃ as lithium salt. The incorporation of the ceramic filler at the lower concentration tested (10% by wt) has practically no effect on the thermal behavior of the samples; whereas, differences were clearly distinguished at a concentration of ceramic material of 20 wt %. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 73: 1023–1030, 1999     

The emerging Hispanic population: a foundation for cancer prevention and control

Although making up only 9% of the U.S. population and concentrated in urban areas of a few states, Hispanics are found throughout the country and represent a mix of historical and cultural backgrounds. This diverse group cuts across racial and ethnic lines, with origins in various countries of Europe and North, Central, and South America. The Hispanic population has several distinguishing demographic characteristics, including its rapid growth rate, relative youth, and low educational and socioeconomic levels. However, considerable differences exist among Hispanic groups, particularly in median age, household size, education, and family income. The majority of Hispanics face barriers to health care access, including a lack of health insurance coverage, underrepresentation in health care fields, and cultural and language differences. These distinct demographic characteristics and barriers have a direct impact on the risk of cancer in Hispanics and on the development of prevention and control strategies. The purpose of this review is to examine the demographic and socioeconomic characteristics of Hispanics and issues of access to health care among this population within the context of cancer prevention and control.