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Nathan Goodyear

Statins use and coronary artery plaque composition: Results from the International Mult... - 0 views

  • Statin use is associated with an increased prevalence and extent of coronary plaques possessing calcium
  • As compared with individuals not taking statins, those taking statins possessed a significantly higher prevalence of obstructive CAD, as well as higher numbers of vessels with obstructive CAD
  • non-calcified plaques (NCP)
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  • non-calcified (NCP), mixed (MP), or calcified (CP) plaque
  • statin use was each associated with a significantly higher prevalence of NCP, MP and CP
  • statin use was associated with increased presence of MP [odds ratio (OR) 1.46, 95% confidence interval (CI) 1.27–1.68, p < 0.001] and CP (OR 1.54, 95% CI 1.36–1.74, p < 0.001], but not NCP
  • statin use was associated with increasing numbers of coronary segments possessing MP and CP but not associated with increasing numbers of coronary segments possessing NCP
  • North America, Europe and Asia
  • A total of 6673 individuals (2413 on statin therapy and 4260 not on statin therapy) comprised the study population
  • we identified a strong association of statin use to coronary artery plaque features
  • statin use was associated with a differentially increased prevalence and extent of MP and CP
  • one potential unifying hypothesis is that rather than regression of coronary plaque, statins may contribute to the conversion of coronary plaque constituents, perhaps by conversion of NCP to plaque possessing calcium
  • Coronary computed tomographic angiography (CCTA)
  • Statin use was associated with a higher frequency of severe coronary artery stenoses as well as numbers of coronary vessels with obstructive CAD
    Study finds statin therapy associated with increased coronary plaque with calcium.
Nathan Goodyear

Statins stimulate atherosclerosis and heart failure: pharmacological mechanisms: Expert... - 0 views

    Statins cause atherosclerosis, not reverse it.  New study describes the mechanism.
Nathan Goodyear

Fructose-1,6-bisphosphate couples glycolytic flux to activation of Ras | Nature Communi... - 0 views

  • glucose deprivation triggers apoptosis47 and vitamin C treatment kills RAS-oncogene expressing tumor cells, but not wild-type RAS containing cells, by inhibition of GAPDH
    New study out of the UK supports the role of glucose in cancer growth and aggressiveness.  This research found that high influx of glucose into the glycolysis pathway upregulated the RAS oncogene via accumulation of the Fructose 1,6 bisphosphonate through the enzyme phosphofructokinase..
Nathan Goodyear

The emerging role of nutrition in Parkinson's disease - 0 views

    Good review of the current data on the role of nutrition in Parkinson's disease.  Take home, a lot of data is conflicting.  But the figure at the end does well to summarize: diet rich in polyphenols in fruits/veggies, carotenoids, resveratrol, Vitamin C, D, E, and MUFA and PUFA are neuroprotective compared to dairy being neurodegenerative.
Nathan Goodyear

Phase I safety trial of intravenous ascorbic acid in patients with severe sepsis - 0 views

  • Padayatty and colleagues showed that high-level ascorbic acid plasma concentrations could only be achieved by intravenous administration
  • No patient in the low or high dose ascorbic acid treatment arms of this study suffered any identifiable adverse event
  • a pharmacologic ascorbic acid treatment strategy in critically ill patients with severe sepsis appears to be safe
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  • subnormal plasma ascorbic acid levels are a predictable feature in patients with severe sepsis
  • Ascorbic acid depletion in sepsis results from ascorbic acid consumption by the reduction of plasma free iron, ascorbic acid consumption by the scavenging of aqueous free radicals (peroxyl radicals), and by the destruction of the oxidized form of ascorbic acid dehydroascorbic acid
  • Sepsis further inhibits intracellular reduction of dehydroascorbic acid, producing acute intracellular ascorbic acid depletion
  • Ascorbic acid treated patients in this study exhibited rapid and sustained increases in plasma ascorbic acid levels using an intermittent every six hours administration protocol
  • Septic ascorbic acid-deficient neutrophils fail to undergo normal apoptosis. Rather, they undergo necrosis thereby releasing hydrolytic enzymes in tissue beds, thus contributing to organ injury
  • We speculate that intravenous ascorbic acid acts to restore neutrophil ascorbic acid levels
  • Repletion of ascorbic acid in this way allows for normal apoptosis, thus, preventing the release of organ damaging hydrolytic enzymes.
    Study finds IV vitamin C in patients with sepsis is very safe and blunts the effects (endothelial damage, end organ damage...) of sepsis.  Of note, the IV vitamin C group reached serum levels of ascorbic acid of 1,592 to 5,722 micromol/L.  The IV groups maintained elevated serum C levels for up to 96 hours post infusion.  
Nathan Goodyear

Enhanced Human Neutrophil Vitamin C Status, Chemotaxis and Oxidant Generation Following... - 0 views

    Vitamin C enhances neutrophil function in study of 14 women.  The study found that their plasma vitamin C status was low.  No increase in new neutrophil generation was noted.  During the study, they only reached 70 micromol/L from the pre-study <50 micromol/L.  I wonder if the study had used higher doses and/or followed longer, they would have seen an increase in the neutrophil numbers?
Nathan Goodyear

Natural killer cells: In health and disease - ScienceDirect - 0 views

    Nice review of NK cells in health and then in states of disease.
Nathan Goodyear

Estrogenic regulation of skeletal muscle proteome: a study of premenopausal women and p... - 0 views

  • Female aging is characterized by menopausal change in sex steroid hormones concomitant to increase in aging-related decrements in skeletal muscle performance that can be attenuated by HRT use
  • The major canonical pathways found to be differentially regulated included mitochondrial dysfunction, oxidative phosphorylation, glycolysis, and TCA-cycle, strong indicators for affected energy metabolism
  • E2 to exert anti-apoptotic effects in muscle progenitor cells by improving mitochondrial function
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  • E2 is a major regulator of human skeletal muscle signaling in women
  • After menopause, when ovarian E2 production is ceased, the prevalence of cardio-metabolic diseases increases. Our result that different trajectories of the energy pathways in the skeletal muscle may be regulated by E2 provides candidate molecules as key targets for future interventions to prevent or treat postmenopausal metabolic dysregulation
    Study finds Estradiol regulates human skeletal muscle cell signaling (mitochondrial function, oxidative phosphorylation, glycolysis, and TCA cycle) in study of pre/post menopause women through proteome analysis. This study would have been complete if they had carried to search beyond that of protein to epigenetics.
Nathan Goodyear - 0 views

    Study suggest the PTSD from the holocaust can be epigenetically transmitted to the offspring of the survivors.
Nathan Goodyear

Persistent epigenetic differences associated with prenatal exposure to famine in humans - 0 views

    Epigenetic as a result of famine exposure prenatally.
Nathan Goodyear

Transgenerational Epigenetic Inheritance: myths and mechanisms - 0 views

    epigenetics can be inheritable transgenerationally via maternal and paternal epigenetic alterations.
Nathan Goodyear

Epigenetics: A New Bridge between Nutrition and Health - 0 views

    7 year old study, though very much still relevant.  Nutrition effects epigenetics.
Nathan Goodyear

Multiple Myeloma Tumor Cells are Selectively Killed by Pharmacologically-dosed Ascorbic... - 0 views

  • Recent reports indicate that a certain ROS concentration is required for high-dose vitamin C to induce cytotoxicity in cancer cells.
  • The generation of ascorbyl- and H2O2 radicals by PAA increases ROS stress in cancer cells
  • In this study, we report that PAA is efficacious in killing MM cells in vitro and in vivo models, which generated levels of 20–40 mM ascorbate and 500 nM ascorbyl radicals after intraperitoneal administration of 4 g ascorbate per kilogram of body weight (Chen et al., 2008), in xenograft MM mice
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  • These data suggest that PAA may show a therapeutic advantage to blood cancers vs solid tumors because of the communication between tumor cells and blood plasma
  • These results strongly suggest that the mechanism of PAA killing of MM cells is indeed iron-dependent
  • These results suggest that PAA administration in SMM may be able to prevent progression to symtomatic MM
  • A recent study by Yun and colleagues demonstrated that vitamin C selectively kills KRAS and BRAF mutant colorectal cancer cells by targeting GAPDH, but spares normal cells
  • RAS family genes show the most frequent mutations in MM. KRAS, NRAS and BRAF are mutated in 22%, 20% and 7% of MM samples
  • the disease stage rather than the mutation of RAS and/or BRAF is the major predictive factor for PAA sensitivity in MM treatment
  • Other molecular mechanisms including ATP depletion and ATM-AMPK signaling have been reported to explain PAA-induced cell death
  • our pilot study also suggested that PAA could overcome drug resistance to bortezomib in MM cells
  • Our findings complement reported studies and further address the mechanism of action using clinical samples in which we observed that PAA killed tumor cells with high iron content, suggesting that iron might be the initiator of PAA cytotoxicity
  • combination of PAA with standard therapeutic drugs, such as melphalan, may significantly reduce the dose of melphalan needed
  • Combined treatment of reduced dose melphalan with PAA achieved a significantly longer progression-free survival than the same dose of melphalan alone.
  • These data also suggest that the bone marrow suppression induced by high-dose melphalan can be ameliorated by the combination of PAA with lower dose of melphalan because of the lack of toxicity of PAA on normal cells with low iron content.
  • if creatinine clearance is <30 mL/min, high dose ascorbic acid should be not administrated.
  • In MM preclinical and clinical studies, ascorbate was used as an adjunct drug and showed controversial results (Harvey et al., 2009, Perrone et al., 2009, Held et al., 2013, Sharma et al., 2012, Nakano et al., 2011, Takahashi, 2010, Sharma et al., 2009, Qazilbash et al., 2008). However, none of these tests used pharmacological doses of ascorbate and intravenous administration
  • Multiple myeloma (MM) is a plasma cell neoplasm.
  • Cameron and Pauling reported that high doses of vitamin C increased survival of patients with cancer
  • pharmacologically dosed ascorbic acid (PAA) 50–100 g (Chen et al., 2008, Padayatty et al., 2004, Hoffer et al., 2008, Padayatty et al., 2006, Welsh et al., 2013), administered intravenously, has potent anti-cancer activity and its role as anti-cancer therapy is being studied at the University of Iowa and in other centers
  • In the presence of catalytic metal ions like iron, PAA administered intravenously exerts pro-oxidant effects leading to the formation of highly reactive oxygen species (ROS), resulting in cell death
  • the labile iron pool (LIP) is significantly elevated in MM cells
  • The survival of CD138+ cells in vitro was significantly decreased following PAA treatment in all 9 MM
  • In contrast, no significant change of cell viability was observed in CD138 BM cells from the same patients
  • The same effect of PAA was also observed in the SMM patients
  • no response to PAA was detected in CD138+ cells from the 2 MGUS patients
  • the combination of melphalan plus PAA showed greater tumor burden reduction than each drug alone, suggesting a synergistic activity between these two drugs
  • Both catalase and NAC protect cells from oxidative damage
  • cells pretreated with NAC and catalase became resistant to PAA even at high doses
  • adding deferoxamine (DFO), an iron chelator, to OCI-MY5 cells before PAA treatment was also sufficient to prevent PAA-induced cellular death
  • iron is essential for PAA to achieve its anti-cancer activity
  • PAA induced early necrosis (Fig. 3A, 60 min) followed by late apoptosis
  • results further indicated that PAA induced mitochondria-mediated apoptosis
  • PAA by reacting with LIP and generating ROS induces mitochondria-mediated apoptosis in which AIF1 cleavage is important for cell death.
  • ROS and H2O2 are well known factors mediating PAA-induced cancer cell death
  • PAA was sensitive to all 9 MMs and 2 SMMs
    animal study finds high-dose, pharmacologic vitamin C found to kill multiple myeloma cells via pro-oxidant effect found in similar studies in dealing with different cancers.
Nathan Goodyear

Oral spore-based probiotic supplementation was associated with reduced incidence of pos... - 0 views

    Study finds spore probiotic for 30 days reduced LPS endotoxin by 42%, while the placebo group found a 36% increase.  As a result, and to no surprise, there was a significant drop in IL-beta.  Also, in the spore probiotic group, there was a 24% reduction in triglycerides.
Nathan Goodyear

The Effect of an EDTA-based Chelation Regimen on Patients With Diabetes Mellitus and Pr... - 0 views

    Only abstract available here, but EDTA chelation found to reduce risk of death, reinfarction, stroke, hospitalization, angina in individuals with diabetes and prior MI from 38% to 25%.
Nathan Goodyear

Calcification in coronary artery disease can be reversed by EDTA-tetracycline long-term... - 0 views

    Study finds that 57% of study participants saw a 14% reduction in coronary calcium score with combined EDTA plus tetracycline.  The reduction may seem modest, and it is, but the delivery method of the EDTA is going to limit the effects.  EDTA should be given IV.
Nathan Goodyear

Interpretation of the Coronary Artery Calcium Score in Combination with Conventional Ca... - 0 views

    A more recent article on the interpretation of the coronary calcium score.  Score alone must be taken in context with the individual.
Nathan Goodyear

What does my patient's coronary artery calcium score mean? Combining information from t... - 0 views

    good review of the coronary calcium score and associated risk estimates.
Nathan Goodyear

Prevention of coronary and stroke events with atorvastatin in hypertensive patients who... - 0 views

    Only abstract available here, but atorvastatin associated with a reduction in cardiovascular events but also associated with increased risk of diabetes.
Nathan Goodyear

Statin use and risk of diabetes mellitus - 0 views

  • An increase in new onset diabetes, i.e., 3% in statin arm and 2.4% in placebo arm was reported. This was accompanied by increase in median value of glycated haemoglobin and was one of the earlier studies to report the increase in new onset diabetes in patients on statins
  • Even after adjustment for potential confounders, statin therapy was associated with an increased risk of new-onset diabetes mellitus
  • Authors suggest that statin-induced diabetes mellitus is a medication class effect
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  • Another study also reported that as compared to placebo, statin group showed a higher risk of physician reported incident diabetes and it was also observed that risk was higher in women as compared to men
  • Meta-analysis of randomized controlled trials by Sattar et al[] involving 91140 non-diabetic patients showed that statin therapy was associated with 9% increased risk of incident diabetes
  • A number of studies showed dose dependent association between statin administration and incident diabetes
  • intensive dose of statins was associated with high incidence of new - onset diabetes
  • Treatment with atorvastatin and simvastatin may be associated with an increased risk of new onset diabetes as compared to pravastatin
  • Increased incidence of diabetes was seen with atorvastatin in the Anglo-Scandinavian Cardiac Outcomes Trial
  • Increased insulin resistance secondary to statins was demonstrated in a prospective non randomised study in patients with coronary bypass surgery
  • downregulation of GLUT4
  • Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial--Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial
  • Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial--Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial
    Great review article of the increased risk of worsening insulin resistance, glycated hemoglobin, and diabetes risk.  Atorvastatin appears to be the worst culprit.  Mechanism partially through a decrease in GLUT4.
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