Study Shorts 5 * Statins – Atherosclerosis & Heart Failure * Arsenic – Moss * EBV – Autoimmune Disease * Progesterone – TBI * Frankincense – Endotoxin

Statins stimulate atherosclerosis and heart failure: pharmacological mechanisms.

This article reviews some of the mechanisms that may lead to increased risk of heart problems from statin medications. They are metabolic poisons affecting vitamin K2 and CoQ10.

“In contrast to the current belief that cholesterol reduction with statins decreases atherosclerosis, we present a perspective that statins may be causative in coronary artery calcification and can function as mitochondrial toxins that impair muscle function in the heart and blood vessels through the depletion of coenzyme Q10 and ‘heme A’, and thereby ATP generation. Statins inhibit the synthesis of vitamin K2, the cofactor for matrix Gla-protein activation, which in turn protects arteries from calcification. Statins inhibit the biosynthesis of selenium containing proteins, one of which is glutathione peroxidase serving to suppress peroxidative stress. An impairment of selenoprotein biosynthesis may be a factor in congestive heart failure, reminiscent of the dilated cardiomyopathies seen with selenium deficiency. Thus, the epidemic of heart failure and atherosclerosis that plagues the modern world may paradoxically be aggravated by the pervasive use of statin drugs. We propose that current statin treatment guidelines be critically reevaluated.”

Phytofiltration of arsenic by aquatic moss (Warnstorfia fluitans)

A study from Stockholm University shows that aquatic moss is remarkably effective at removing arsenic from water.

“This work investigates whether aquatic moss (Warnstorfia fluitans) originating from an arsenic (As)-contaminated wetland close to a mine tailings impoundment may be used for phytofiltration of As…..
Results indicated that W. fluitans removed up to 82% of As from the water within one hour when 1 μM arsenate was added in the absence of nutrients. The removal time increased with greater nutrient and As concentrations. Up to 100 μM As had no toxic effect on the plant biomass. Both arsenite and arsenate were removed from the solution to similar extents and, independent of the As species added, more arsenate than arsenite was found in the plant. Of the As taken up, over 90% was firmly bound to the tissue, a possible mechanism for resisting high As concentrations. Arsenic was both absorbed and adsorbed by the moss, and twice as much As was found in living parts as in dead moss tissue. This study revealed that W. fluitans has potential to serve as a phytofilter for removing As from As-contaminated water without displaying any toxic effects of the metalloid.”

Transcription factors operate across disease loci, with EBNA2 implicated in autoimmunity

Epstein Barre virus (mono) seems to be associated with a number of autoimmune diseases. Researchers found that the virus interacts with DNA in regions known to be related to systemic lupus erythematous, multiple sclerosis, rheumatoid arthritis, juvenile idiopathic arthritis, inflammatory bowel disease, celiac disease, and type 1 diabetes.

“Explaining the genetics of many diseases is challenging because most associations localize to incompletely characterized regulatory regions. Using new computational methods, we show that transcription factors (TFs) occupy multiple loci associated with individual complex genetic disorders….. Strikingly, nearly half of systemic lupus erythematosus risk loci are occupied by the Epstein–Barr virus EBNA2 protein and many coclustering human TFs, showing gene–environment interaction. Similar EBNA2-anchored associations exist in multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease, type 1 diabetes, juvenile idiopathic arthritis and celiac disease. Instances of allele-dependent DNA binding and downstream effects on gene expression at plausibly causal variants support genetic mechanisms dependent on EBNA2. Our results nominate mechanisms that operate across risk loci within disease phenotypes, suggesting new models for disease origins.”

Repurposing and repositioning neurosteroids in the treatment of traumatic brain injury: A report from the trenches

Emory University team working on development of progesterone and vitamin D treatments of TBI. There have been a number of studies on progesterone and TBI, without great results as far as I recall.

“The field of neuroprotection after brain injuries has been littered with failed clinical trials. Finding a safe and effective treatment for acute traumatic brain injury remains a serious unmet medical need. Repurposing drugs that have been in use for other disorders is receiving increasing attention as a strategy to move candidate drugs more quickly to trial while reducing the very high cost of new drug development. This paper describes our own serendipitous discovery of progesterone’s neuroprotective potential, and the strategies we are using in repurposing and developing this hormone for use in brain injuries—applications very different from its classical uses in treating disorders of the reproductive system. We have been screening and testing a novel analog that maintains progesterone’s therapeutic properties while overcoming its physiochemical challenges, and testing progesterone in combination treatment with another pleiotropic hormone, vitamin D. Finally, our paper, in the context of the problems and pitfalls we have encountered, surveys some of the factors we found to be critical in the clinical translation of repurposed drugs.”

Protective effect of Casperome®, an orally bioavailable frankincense extract, on lipopolysaccharide-induced systemic inflammation in mice

I believe that endotoxin/lipopolysaccharide is one of the main causes of disease. So anything that protects against endotoxin grabs my interest. This study shows that a frankincense extract protects mice from the acute effects of endotoxin.

“LPS (endotoxin) treatment caused a decrease in body temperature, blood glucose levels, liver glycogen content, and biotransformation capacity along with an increase in serum cytokine levels and oxidative stress in various organs. Additionally, apoptotic processes were increased in spleen besides a pronounced immune cell infiltration in both liver and spleen. Pretreatment with Casp significantly improved health status, blood glucose values, and body temperature of the animals, while serum levels of pro-inflammatory cytokines and oxidative stress in all organs tested were significantly diminished. Finally, apoptotic processes in spleen, liver glycogen loss, and immune cell infiltration in liver and spleen were distinctly reduced. Casp also appears to induce various cytochromeP450 isoforms, thus causing re-establishment of liver biotransformation capacity in LPS-treated mice.

Conclusion: Casp displayed anti-inflammatory, anti-oxidative, and hepatoprotective effects. Thus, orally bioavailable frankincense extracts may serve as a new supportive treatment option in acute systemic inflammation and accompanied liver dysfunction.”