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Nathan Goodyear

Homocysteine and Endothelial Dysfunction: A Link with Cardiovascular Disease - 0 views

jn.nutrition.org/...369.full.pdf+html

homocysteine CVD endothelial dysfunction cardiovascular disease ROS reactive oxygen species

shared by Nathan Goodyear on 25 Sep 12 - No Cached
  • Nathan Goodyear on 25 Sep 12
     
    No surprise that homocysteine is associated with vascular dysfunction, when elevated;  But the mechanism is elucidated here through ROS generation.
Nathan Goodyear

Alzheimer's Disease Clinical and Research Update for Health Care Practitioners - 0 views

www.ncbi.nlm.nih.gov/...PMC3776389

Alzheimer's disease cognition memory Alzheimers brain brain health alpha-GPC phosphatidyl serine Huperzine A choline

shared by Nathan Goodyear on 26 Sep 17 - No Cached
  • Alpha GPC, phosphatidylserine, Huperzine A, and choline show promise as nutraceutical agents for enhancing cognitive performance and slowing cognitive decline
  • Alpha GPC, also known as L-Alpha Glycerylphosphorylcholine, a naturally occurring form of choline, acts as a parasympathomimetic acetylcholine precursor and has shown promise in improving cognitive symptoms related to AD, vascular dementia, and multi-infarct dementia
  • Phosphatidylserine is a widely abundant anionic phospholipid in the human body and has been shown to improve age-related cognitive changes
  • ...2 more annotations...
  • Huperzine A (a natural cholinesterase inhibitor) has been linked to improved memory performance in elderly people with benign forgetfulness, as well as patients with AD and vascular dementia
  • Cholinesterase inhibitors have been shown to have neuroprotective properties in patients with mild [37] as well as moderate-to-advanced AD
  • Nathan Goodyear on 26 Sep 17
     
    good review of treatment for Alzheimer's, both prescription and natural.
Nathan Goodyear

NETosis and Neutrophil Extracellular Traps in COVID-19: Immunothrombosis and Beyond - PMC - 0 views

www.ncbi.nlm.nih.gov/...PMC8924116

cancer NETosis SARS-CoV-2 COVID COVID-19 COVID19 platelets

shared by Nathan Goodyear on 18 Apr 23 - No Cached
  • Pneumonia is a typical symptom of COVID-19 infection, while acute respiratory distress syndrome (ARDS) and multiple organ failure are common in severe COVID-19 patients
  • NETs are important for preventing pathogen invasion, their excessive formation can result in a slew of negative consequences, such as autoimmune inflammation and tissue damage
  • SARS-CoV-2 infection has also been linked to increased neutrophil-to-lymphocyte ratios, which is associated with disease severity and clinical prognosis
  • ...40 more annotations...
  • NETosis is a special form of programmed cell death in neutrophils, which is characterized by the extrusion of DNA, histones, and antimicrobial proteins in a web-like structure known as neutrophil extracellular traps (NETs)
    • Nathan Goodyear
      Nathan Goodyear on 23 Apr 23
       
      Definition
  • increased generation of reactive oxygen species (ROS) is a crucial intracellular process that causes NETosis
  • Another indirect route of SARS-CoV-2-induced NET production is platelet activation
  • When NETs are activated in the circulation, they can also induce hypercoagulability and thrombosis
  • In COVID-19, major NET protein cargos of NETs (i.e., NE, MPO, and histones) are significantly elevated.
  • SARS-CoV-2 can also infect host cells through noncanonical receptors such as C-type lectin receptors
  • Immunopathological manifestations, including cytokine storms and impaired adaptive immunity, are the primary drivers behind COVID-19, with neutrophil infiltration being suggested as a significant cause
  • NETosis and NETs are increasingly recognized as causes of vascular injury
  • SARS-CoV-2 and its components (e.g., spike proteins and viral RNA) attach to platelets and increase their activation and aggregation in COVID-19, resulting in vascular injury and thrombosis, both of which are linked to NET formation
    • Nathan Goodyear
      Nathan Goodyear on 23 Apr 23
       
      Connects SARS-CoV-2 to TLR on Platelets to NETosis to metastasis.
  • NET formation may be caused by activated platelets rather than SARS-CoV-2 itself
  • NETosis, leading to aberrant immunity such as cytokine storms, autoimmune disorders, and immunosuppression.
  • early bacterial coinfections were more prevalent in COVID-19 patients than those infected with other viruses
  • NETosis and NETs may also have a role in the development of post COVID-19 syndromes, including lung fibrosis, neurological disorders, tumor growth, and worsening of concomitant disease
    • Nathan Goodyear
      Nathan Goodyear on 23 Apr 23
       
      NETosis-> tumor growth
  • NETs and other by-products of NETosis have been shown to act as direct inflammation amplifiers. Hyperinflammation
  • “cytokine storm”
  • SARS-CoV-2 drives NETosis and NET formation to allow for the release of free DNA and by-products (e.g., elastases and histones). This may trigger surrounding macrophages and endothelial cells to secrete excessive proinflammatory cytokines and chemokines, which, in turn, enhance NET formation and form a positive feedback of cytokine storms in COVID-19
    • Nathan Goodyear
      Nathan Goodyear on 23 Apr 23
       
      Cycle of hyperinflammation
  • NET release enables self-antigen exposure and autoantibody production, thereby increasing the autoinflammatory response
  • patients with COVID-19 who have higher anti-NET antibodies are more likely to be detected with positive autoantibodies [e.g., antinuclear antibodies (ANA) and anti-neutrophil cytoplasmic antibodies (ANCA)]
  • COVID-19 NETs may act as potential inducers for autoimmune responses
  • have weakened adaptive immunity as well as a high level of inflammation
    • Nathan Goodyear
      Nathan Goodyear on 23 Apr 23
       
      Immunomodulation
  • tumor-associated NETosis and NETs promote an immunosuppressive environment in which anti-tumor immunity is compromised
  • NETs have also been shown to enhance macrophage pyroptosis in sepsis
  • facilitating an immunosuppressive microenvironment
  • persistent immunosuppression may result in bacterial co-infection or secondary infection
  • can enhance this process by interacting with neutrophils through toll-like receptor 4 (TLR4), platelet factor 4 (PF4), and extracellular vesicle-dependent processes
  • NET-induced immunosuppression in COVID-19 in the context of co-existing bacterial infection
  • Following initial onset of COVID-19, an estimated 50% or more of COVID-19 survivors may develop multi-organ problems (e.g., pulmonary dysfunction and neurologic impairment) or have worsening concomitant chronic illness
  • NETs in the bronchoalveolar lavage fluid of severe COVID-19 patients cause EMT in lung epithelial cells
  • decreased E-cadherin (an epithelial marker) expression
    • Nathan Goodyear
      Nathan Goodyear on 23 Apr 23
       
      Leads to emt
  • COVID-19 also has a long-term influence on tumor progression
  • Patients with tumors have been shown to be more vulnerable to SARS-CoV-2 infection and subsequent development of severe COVID-19
  • patients who have recovered from COVID-19 may have an increased risk of developing cancer or of cancer progression and metastasis
  • awaken cancer cells
  • NETs have been shown to change the tumor microenvironment
  • enhance tumor progression and metastasis
  • vitamin C has been tested in phase 2 clinical trials aimed at reducing COVID-19-associated mortality by reducing excessive activation of the inflammatory response
  • vitamin C is an antioxidant that significantly attenuates PMA-induced NETosis in healthy neutrophils by scavenging ROS
  • vitamin C may also inhibit NETosis and NET production in COVID-19
  • Metformin
  • Vitamin C
  • Nathan Goodyear on 18 Apr 23
     
    NETosis intimately involved in progressive COVID, long COVID, autoimmunity, and cancer
spineneuro

Dr. Vipul Gupta for Stroke & Neurovascular Diseases - 101 Press Release - 0 views

www.101pressrelease.com/-stroke-neurovascular-diseases

Dr. Vipul Gupta neuro-interventional radiology neuroradiology brain surgery Artemis

shared by spineneuro on 23 Feb 22 - No Cached
  • spineneuro on 23 Feb 22
     
    The stroke program by Dr. Vipul Gupta brings collectively leading professionals in vascular neurology, neurosurgery, neurocritical care, neuro-interventional radiology, neuroradiology medicine that focus on diagnosing and treating people with disorders affecting vessels of the brain and spinal cord.
Nathan Goodyear

EDTA chelation therapy in the treatment of vascula... [J Cardiovasc Nurs. 1996] - PubMe... - 0 views

www.ncbi.nlm.nih.gov/...8820322

chelation edta therapy cardiovascular disease

shared by Nathan Goodyear on 14 Feb 11 - No Cached
  • EDTA chelation therapy in the treatment of vascular disease.
  • Nathan Goodyear on 14 Feb 11
     
    Chelation as therapy for cardiovascular disease
Nathan Goodyear

Folates and Cardiovascular Disease -- Verhaar et al. 22 (1): 6 -- Arteriosclerosis, Thr... - 0 views

atvb.ahajournals.org/...6

cardiovascular folates disease folate folic acid

shared by Nathan Goodyear on 29 Apr 11 - No Cached
  • benefits of folates independent of homocysteine lowering have also been reported. Potential mechanisms include antioxidant actions, effects on cofactor availability, or direct interactions with the enzyme endothelial NO synthase
  • beneficial effects of folates on cardiovascular risk
  • Nathan Goodyear on 29 Apr 11
     
    Folate improves cardiovascular disease risk
Nathan Goodyear

Journal of Clinical Investigation -- Oxidation of tetrahydrobiopterin leads to uncoupli... - 0 views

www.jci.org/14172

tetrahydrobiopterin cardiovascular disease hypertension

shared by Nathan Goodyear on 29 Apr 11 - No Cached
  • Tetrahydrobiopterin is a critical cofactor for the NO synthases
  • at hypertension produces a cascade involving production of ROSs from the NADPH oxidase leading to oxidation of tetrahydrobiopterin and uncoupling of endothelial NO synthase (eNOS). This decreases NO production and increases ROS production from eNOS
  • Tetrahydrobiopterin oxidation may represent an important abnormality in hypertension
  • ...1 more annotation...
  • Treatment strategies that increase tetrahydrobiopterin or prevent its oxidation may prove useful in preventing vascular complications of this common disease.
  • Nathan Goodyear on 29 Apr 11
     
    tetrahydrobiopterin deficiency plays role in cardiovasular disease
Nathan Goodyear

Inborn-like errors of metabolism are determinants of breast cancer risk, clinical respo... - 0 views

www.ncbi.nlm.nih.gov/...PMC6114970

cancer metabolism breast cancer glutamine glutamate aspartate oncogenes

shared by Nathan Goodyear on 24 Sep 18 - No Cached
  • We now recognize that human cancers evolve in an environment of metabolic stress. Rapidly proliferating tumor cells deprived of adequate oxygen, nutrients, hormones and growth factors up-regulate pathways that address these deficiencies to overcome hypoxia (HIF), vascular insufficiency (VEGF), growth factor deprivation (EGFR, HER2) and the loss of hormonal support (ER, PR, AR) all to enhance survival and proliferation
  • RAS, PI3K, TP53 and MYC
  • The results suggest that breast cancer could be preceded by systemic subclinical disturbances in glucose-insulin homeostasis characterized by mild, likely asymptomatic, IEM-like biochemical changes
  • ...16 more annotations...
  • The process would include variable periods of hyperinsulinemia with the consequent systemic MYC activation of glycolysis, glutaminolysis, structural lipidogenesis and further exacerbation of hypoglycemia, the result of MYC's known role as an inhibitor of liver gluconeogenesis
  • The metabolic changes we describe in breast cancer arise in concert with IEM-like changes in oxidative phosphorylation as detected by increased values of the ratio lactate/pyruvate (Supplementary Table 2A, 2B) characteristic of Ox/Phos deficiency [25]. In our study, 76% (70/92) of the European breast cancer patients had lactate/pyruvate ratios values higher than the normal value of 25.8
  • four-fold higher frequency of cancer (including breast) in patients with energy metabolism disorders
  • growing recognition that cancer cells differ from their normal counterparts in their use of nutrients, synthesis of biomolecules and generation of energy
  • glutamine concentrations in the cancer patients were reduced to nearly 1/8 of the levels observed in the normal population
  • blood concentrations of aspartate (p = 1.7e-67, FDR = 8.3e-67) (Figure ​(Figure1E)1E) and glutamate (p = 6.4e-96, FDR = 6.2e-95) (Figure ​(Figure1F)1F) were nearly 10 fold higher than the normal ranges of 0–5 μM/L and 40 μM/L, respectively
  • glutamine consumption associated with parallel increases in glutamate and aspartate (Figure ​(Figure1A1A red arrows) is considered a hallmark of MYC-driven “glutaminolysis”
  • Gln/Glu ratio inversely correlates with i- late stage metabolic syndrome and with ii- increased chance of death
  • changes in glutamine consumption, reflected by the Gln/Glu ratio could provide a metabolic link between breast cancer initiation and diabetes, reflective of a systemic metabolic reprogramming from glucose to glutamine as the preferred source of precursors for biosynthetic reactions and cellular energy
  • lower Gln/Glu ratios inversely correlated with insulin resistance and the risk of diabetes
  • the metabolic dependencies of cancer characterized by excessive glycolysis, glutaminolysis and malignant lipidogenesis, previously considered a consequence of local tumor DNA aberration [23] could, instead, represent a systemic biochemical aberration that predates and very likely promotes tumorigenesis
  • these metabolic disturbances would be expected to remain extant after therapeutic interventions
  • accumulation of very long chain acylcarnitines such as C14:1-OH (p = 0.0, FDR = 0.0), C16 (p = 0.0, FDR = 0.0), C18 (p = 0.0, FDR = 0.0) and C18:1 (p = 1.73e-322, FDR = 1.16-321) and lipids containing VLCFA (lysoPC a C28:0) (p = 1.14-e95, FDR = 1.65e-95) in the blood of breast and colon cancer patients
  • Among the most powerful metabolic equations for MYC-activation is that which links the widely used MYC-driven desaturation marker ratio of SFA/MUFA to the MYC glutaminolysis-associated ratio of (Asp/Gln)
  • liver dysfunction shares many features with both IEM and cancer suggesting a role for hepatic dysfunction in carcinogenesis
  • cancer “conscripts” the human genome to meet its needs under conditions of systemic metabolic stress
  • Nathan Goodyear on 24 Sep 18
     
    Breast cancer is a metabolic disease.  Now, where have I heard that cancer is a metabolic disease?
Nathan Goodyear

alpha-Lipoic acid and ascorbate prevent LDL... [Mol Cell Biochem. 2008] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...18026819

alpha lipoic acid vitamin C oxidized LDL LDL cholesterol CVD cardiovascular disease

shared by Nathan Goodyear on 20 Feb 13 - No Cached
  • Nathan Goodyear on 20 Feb 13
     
    Alpha lipoic acid and vitamin C shown to protect against oxidized LDL.  When discussing the negative effects of LDL, the real risk associated with LDL is whether it is oxidized or not.  Alpha lipoic acid and Vitamin C prevent this and thus protect the vascular endothelium.
Nathan Goodyear

http://orthomolecular.org/library/jom/1992/pdf/1992-v07n01-p005.pdf - 0 views

orthomolecular.org/...1992-v07n01-p005.pdf

vitamin C CVD Pauling Linus Pauling Lp(a) cardiovascular disease hypertension

shared by Nathan Goodyear on 16 Jan 17 - No Cached
  • Nathan Goodyear on 16 Jan 17
     
    This is the unified paper theory of CVD and vitamin C as published by Pauling and Rath.  Vitamin C deficiency results in a decrease in the integrity and stability of the vascular wall.  Chronic deficiency results in in an increase in and accumulation of Lp(a) which leads to atherosclerotic plaques.
Nathan Goodyear

JAMA Network | Archives of Neurology | Insulin Resistance in Cognitive ImpairmentThe In... - 0 views

archneur.jamanetwork.com/article.aspx

IR insulin resistance brain neurodegenerative disorders Alzheimer's disease obesity neurology dementia

shared by Nathan Goodyear on 11 Jun 12 - No Cached
  • Nathan Goodyear on 11 Jun 12
     
    insulin resistance shown to play a role in cognitive impairment.  Rising Insulin resistance is not just associated with obesity, but also brain dysfunction similar to that in strokes.  This indicates a vascular component in the cognitive function.  The same rise in obesity will likely result in a rise in neurodegenerative disorders.
Nathan Goodyear

Differential regulation of endothelium behavior by progesterone and medroxyprogesterone... - 0 views

joe.endocrinology-journals.org/...179.abstract

progesterone medroxyprogesterone acetate medroxyprogesterone hormone hormones women cardiovascular disease HRT

shared by Nathan Goodyear on 04 Feb 14 - No Cached
  • Nathan Goodyear on 04 Feb 14
     
    No surprise that progesterone and the synthetic progestin medroxyprogesterone acetate (MPA) have different effects on the vascular endothelium. MPA inhibits NO production, whereas Progesterone maintains NO production.  MPA promoted platelet adhesion whereas Progesterone did not--significant implication in plaque formation.
Nathan Goodyear

Catcholamine and nitric oxide systems as targets of... [Life Sci. 2000] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...11205890

Pb lead NO catecholamines epinephrine norepinephrine hypertension CVD cardiovascular disease

shared by Nathan Goodyear on 16 Sep 14 - No Cached
  • Nathan Goodyear on 16 Sep 14
     
    Pb reduced NO, increased epinephrine and norepinephrine, increased vascular resistance and RAA system which resulted in hypertension.
Nathan Goodyear

Association of testosterone with estrogen abolishes the beneficial effects of estrogen ... - 0 views

ajpheart.physiology.org/...ajpheart.00681.2014

Testosterone Estrogen CVD cardiovascular health disease heart hormone hormones women female

shared by Nathan Goodyear on 02 Feb 15 - No Cached
  • Nathan Goodyear on 02 Feb 15
     
    Testosterone reduced the vascular benefits of Estrogen (conjugated equine Estrogen) in female rat model.  Testosterone is seeing widespread use in women with very little positive data.  In fact, the majority of data points to poor metabolic effects and poor outcomes.
Nathan Goodyear

Resistance-Based Interval Exercise Acutely Improves Endothelial Function In Type 2 Diab... - 0 views

ajpheart.physiology.org/...ajpheart.00398.2016

exercise interval training diabetes CVD cardiovascular disease heart

shared by Nathan Goodyear on 11 Oct 16 - No Cached
  • Nathan Goodyear on 11 Oct 16
     
    resistance/cardio interval training found to improve vascular endothelial function.
Nathan Goodyear

Increased Vascular Inflammation in Early Menopausal Women Is Associated with Hot Flush ... - 0 views

jcem.endojournals.org/...E760.abstract

inflammation cytokines hot flashes menopause women cardiovascular disease severity

shared by Nathan Goodyear on 25 May 12 - No Cached
  • Nathan Goodyear on 25 May 12
     
    increased inflammatory markers associated with increased hot flash severity in menopausal women.  This is also associated with increased cardiovascular disease. Interesting that progesterone has anti-inflammatory properties.  So, therapy to reduce hot flashes should include inflammation reduction.
Nathan Goodyear

Huperzine A in the Treatment of Alzheimer's Disease and Vascular Dementia: A Meta-Analysis - 0 views

www.hindawi.com/...363985

dementia Alzheimer's alzheimer's disease alzheimer disease huperzine A

shared by Nathan Goodyear on 30 Sep 14 - No Cached
  • Nathan Goodyear on 30 Sep 14
     
    Good review of the data on Huperzine A and Alzheimer's dementia.
Nathan Goodyear

The relation between hypomagnesaemia and vascular stiffness in renal transplant recipients - 0 views

ndt.oxfordjournals.org/...ndt.gfq728.abstract

Magnesium arterial disease cardiovascular artery

shared by Nathan Goodyear on 17 Apr 11 - No Cached
  • Serum magnesium is an independent predictor of arterial stiffness in RTR, especially in patients >55 years.
  • Nathan Goodyear on 17 Apr 11
     
    Magnesium deficiency and arterial disease
Nathan Goodyear

Apolipoprotein B and Cardiovascular Disease Risk: Position Statement from the AACC Lipo... - 0 views

clinchem.aaccjnls.org/...407

apo B Apolipoprotein B cardiovascular disease LDL cholesterol

shared by Nathan Goodyear on 13 Dec 17 - No Cached
  • Nathan Goodyear on 13 Dec 17
     
    ApoB is a better measure of risk than LDL.
Nathan Goodyear

Testosterone: a vascular hormone in health and disease - 0 views

joe.endocrinology-journals.org/...JOE-12-0582.full.pdf+html

low T low Testosterone testosterone low cardiovascular cardiovascular disease CVD health hormone hormones men male

shared by Nathan Goodyear on 23 Apr 13 - No Cached
  • Nathan Goodyear on 23 Apr 13
     
    testosterone therapy has tremendous cardiovascular benefit in men with low T.  The key here is physiologic replacement of Testosterone.  Testosterone is a vasodilator and anti-inflammatory agent in men with low T.  Testosterone therapy improves cardiac function in those with DHF and angina.  Testosterone is found to be a Ca++ channel blocker--anyone say hypertension treatment?
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