Matrix Metalloproteinase Gene Delivery for Liver Fibrosis

The resolution of advanced liver fibrosis has been recently recognized to be possible, if the causative stimuli are successfully removed. However, whether complete resolution from cirrhosis, the end stage of liver fibrosis, can be achieved is still questionable. Delivery of interstitial collagenases, such as matrix metalloproteinase (MMP)-1, in the liver could be an attractive strategy to treat advanced hepatic fibrosis from the view point that the imbalance between too few interstitial collagenases and too many of their inhibitors is the main obstacle to the resolution from fibrosis. Remodeling of hepatic extracellular matrix by delivered interstitial collagenases also facilitates the disappearance of activated hepatic stellate cells, the main matrix-producing cells in the liver, and promotes the proliferation of hepatocytes. This review will focus on the impact of the gene delivery of MMPs for the treatment of advanced liver fibrosis while discussing other current therapeutic strategies for liver fibrosis, and on the need for the development of a safe and effective delivery system of MMPs

Evolution of Female Preference for Younger Males

Previous theoretical work has suggested that females should prefer to mate with older males, as older males should have higher fitness than the average fitness of the cohort into which they were born. However, studies in humans and model organisms have shown that as males age, they accumulate deleterious mutations in their germ-line at an ever-increasing rate, thereby reducing the quality of genes passed on to the next generation. Thus, older males may produce relatively poor-quality offspring. To better understand how male age influences female mate preference and offspring quality, we used a genetic algorithm model to study the effect of age-related increases in male genetic load on female mate preference. When we incorporate age-related increases in mutation load in males into our model, we find that females evolve a preference for younger males. Females in this model could determine a male's age, but not his inherited genotype nor his mutation load. Nevertheless, females evolved age-preferences that led them to mate with males that had low mutation loads, but showed no preference for males with respect to their somatic quality. These results suggest that germ-line quality, rather than somatic quality, should be the focus of female preference in good genes models

2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease

The recommendations listed in this document are, whenever possible, evidence based. An extensive evidence review was conducted as the document was compiled through December 2008. Repeated literature searches were performed by the guideline development staff and writing committee members as new issues were considered. New clinical trials published in peer-reviewed journals and articles through December 2011 were also reviewed and incorporated when relevant. Furthermore, because of the extended development time period for this guideline, peer review comments indicated that the sections focused on imaging technologies required additional updating, which occurred during 2011. Therefore, the evidence review for the imaging sections includes published literature through December 2011

Current antioxidant molecular therapies for oxidative stress-related ailments

Oxidative cell damage is a natural occurring phenomenon due to the aerobic conditions where cells are embedded; however, such injury can efficiently be controlled and repaired by the inherent antioxidants of the cell. When the oxidant/antioxidant balance is disrupted towards the former by any chemical, biological or physical insult a pathological state could be developed, therefore, an extensive list of compounds with proved or assumed antioxidants Properties has largely been used for improving or restoring the health status. Pharmacological therapies as well as dietary or complementary therapies are continuously being investigated for the counteracting of the harmful or damaging effects of oxidation in cells or tissues. However, critical antioxidant levels are not always achieved at the target damaged cells by these approaches; on the other side, the expression of recombinant antioxidant genes specifically directed to the afflicted cell by gone delivery has shown remarkable results. In this review we summarize the literature focused on some of the current antioxidant molecular pharmacological strategies with particular emphasis to the gend transfer protocols involved in the treatment of oxidative stress-related disorders. © 2008 Bentham Science Publishers Ltd