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Nathan Goodyear

Phase I clinical trial of the flavonoid quercetin: pharmacokinetics and evidence for in vivo tyrosine kinase inhibition. | Clinical Cancer Research - 0 views

clincancerres.aacrjournals.org/...659.long

pharmacokinetics dosing cancer Quercetin

shared by Nathan Goodyear on 27 Aug 20 - No Cached
  • Nathan Goodyear on 27 Aug 20
     
    Great phase 1 pharmacokinetic study on Quercetin dosing.
Nathan Goodyear

The effect of parenteral selenium on outcomes of mechanically ventilated patients following sepsis: a prospective randomized clinical trial | Annals of Intensive Care | Full Text - 0 views

annalsofintensivecare.springeropen.com/...s13613-015-0071-y

selenium glutathione peroxidase glutathione sepsis

shared by Nathan Goodyear on 30 May 20 - No Cached
  • Nathan Goodyear on 30 May 20
     
    selenium IV in sepsis patients increased glutathione peroxidase and reduced ventilator associated pneumonia.
Nathan Goodyear

MicroRNAs Derived from Extracellular Vesicles: Keys to Understanding SARS-CoV-2 Vaccination Response in Cancer Patients? - Abstract - Europe PMC - 0 views

europepmc.org/...PMC10452664

COVID-19 COVID19 cancer COVID SARS-CoV-2

shared by Nathan Goodyear on 01 Sep 23 - No Cached
  • the clinical trials for COVID-19 vaccines did not include cancer patients, leaving a knowledge gap about how vaccination affects this vulnerable population
Nathan Goodyear

Red yeast rice induces less muscle fatigue symptom than simvastatin in dyslipidemic patients: a single center randomized pilot trial | BMC Cardiovascular Disorders | Full Text - 0 views

bmccardiovascdisord.biomedcentral.com/...s12872-017-0560-z

cancer red yeast rice simvastatin

shared by Nathan Goodyear on 01 Sep 23 - No Cached
  • Nathan Goodyear on 01 Sep 23
     
    Less side effects with red yeast rice.
Nathan Goodyear

The Role of Vitamin C in Human Immunity and Its Treatment Potential Against COVID-19: A Review Article - PMC - 0 views

www.ncbi.nlm.nih.gov/...PMC9925039

COVID-19 SARS-CoV-2 COVID WBC ascorbic acid vitamin C

shared by Nathan Goodyear on 01 Sep 23 - No Cached
  • vitamins A, B, C, E, B6, B12, folate, zinc, iron, copper, and selenium
  • White blood cells, including neutrophils and monocytes, accumulate concentrations of vitamin C up to 100 times greater than that of plasma
  • Vitamin C is a crucial component of both the innate (nonspecific) and adaptive (specific) portions of the immune system
  • ...52 more annotations...
  • play a role during the initial chemotactic response of neutrophils shortly after infection
  • following vitamin C supplementation, a 20% increase in neutrophil chemotactic activity was observed
  • also contributes to the phagocytosis and killing of microbes by neutrophils
  • low levels of vitamin C occurring in high-stress situations
  • maturation, proliferation, and viability of T cells have all been shown to be upregulated by the presence of normal physiologic concentrations of vitamin C
  • Vitamin C has been shown to directly affect the number of Igs released from B cells
  • vitamin C among healthy young adult males showed a significant increase in serum levels of IgA, IgG, and IgM
  • effects of high-dose vitamin C on cytokine levels in cancer patients, finding decreased amounts of the cytokines Interleukin-1 alpha (IL-1 alpha), IL-2, IL-8, and tumor necrosis factor-alpha (TNF-alpha) after high-dose vitamin C infusion
  • when vitamin C was supplemented with vitamin E in healthy adults, it increased the production of cytokines IL-1 beta and TNF-alpha
  • vitamin C acts to modulate the levels of cytokines to prevent them from fluctuating in either direction
  • vitamin C also acts as an important antioxidant to the cells of the immune system.
  • human leukocytes, neutrophils, in particular, possess the ability to transport the oxidized form of vitamin C across its membrane to use as a defense mechanism against ROS produced during an immune response
  • Vitamin C also can recover other endogenous antioxidants in the body such as vitamin E and glutathione, returning them to their active state
  • vitamin C can decrease the activation of NF-kB
  • can reduce harmful nitrogen-based compounds such as N-nitrosamines and nitrosamides, both of which are carcinogenic 
  • subjects taking oral vitamin C supplementation saw a 60% to 90% reduction in oxidative stress compared to a placebo control
  • subjects infused with vitamin C alone had a 516% increase in glutathione levels compared to subjects not provided the 500 mg daily supplementation
  • hydroxylating proline and lysine
  • mature and stabilize the tissue of a healing wound
  • healing
  • oral surgery
  • improved soft tissue regeneration
  • vitamin C increases the mRNA levels of type I and type III collagen in the human dermis
  • Studies have demonstrated that those with low levels of vitamin C are at a significantly higher risk of respiratory infection compared to those with normal levels
  • viral cold duration was reduced by about 8% in adults and 13.5% in children using prophylactic daily doses of 200 mg of oral vitamin C
  • prophylactically supplementing vitamin C decreases the risk of infection with respiratory viruses such as the common cold
  • combined with probiotics, oral vitamin C supplementation showed a 33% decrease in the incidence of respiratory tract infections in preschool-age children [
  • high-dose oral supplementation of vitamin C managed to prevent or reduce symptoms if taken before or just after the onset of cold- or flu-like symptoms
  • improvements in oxygen saturation and decreased IL-6 levels (a marker of inflammation) in the treatment group compared to the control group
  • 8 g doses of oral vitamin C
  • there is a negative correlation between age and serum levels of vitamin C
  • Patients with COVID-19 will likely also experience depletion in serum levels of vitamin C as a direct result of the upregulation of the immune system to combat the infection
  • Colunga et al. suggested that oral vitamin C can be combined with oral Quercetin, an antiviral flavonoid, to improve Quercetin’s ability to block viral membrane fusion of SARS-CoV-2
  • high doses of 1-2 g/day of oral vitamin C could prevent other upper respiratory infections
  • It appears vitamin C supplementation by itself does not provide a striking benefit in preventing COVID-19 infection for those without a deficiency
    • Nathan Goodyear
      Nathan Goodyear on 01 Sep 23
       
      Flawed statement. What is normal? Vitamin D. Many variables effect levels and dose, including the two compartment kinetics and absorption.
  • Hiedra et al. were able to show decreases in inflammatory biomarkers, such as D-dimer and ferritin
  • some evidence to support that prophylactic use of vitamin C helps reduce the severity of respiratory infection symptoms once a subject has already been infected
  • oral vitamin C in combination with zinc provided the largest amount of antibody titers 42 days
  • linear relationship between days of vitamin C therapy and survival duration
  • other studies were unable to find any definitive improvement concerning therapy with vitamin C
    • Nathan Goodyear
      Nathan Goodyear on 01 Sep 23
       
      Either these studies are designed to fail or the authors are lacking some basic understanding of pharmacokinetics and pharmacodynamics with vitamin C.
  • Fowler et al. aimed to see if a high-dose vitamin C infusion would benefit patients affected by ARDS, but they were unable to conclude that vitamin C infusion, compared to a placebo, could decrease vascular inflammation and damage in ARDS
    • Nathan Goodyear
      Nathan Goodyear on 01 Sep 23
       
      At what dose, duration, frequency???
  • in a sample of 67 COVID-19-positive ICU patients, 82% of them displayed plasma vitamin C levels below 0.4 mg/dL
    • Nathan Goodyear
      Nathan Goodyear on 01 Sep 23
       
      They are kind of make the point from my earlier note.
  • continuous vitamin C infusion at a rate of 60 mg/kg/day for four days decreased the need for mechanical ventilation and vasopressor use but had no significant effect on overall mortality
    • Nathan Goodyear
      Nathan Goodyear on 01 Sep 23
       
      Again, designed to fail or ignorance designed the study which failed
  • Carr et al. suggested that high-dose IV vitamin C is most effective when treating sepsis as septic patients receiving the normal daily recommendations through diet still showed decreased vitamin C levels
  • High-dose IV vitamin C treatment has also been shown by Kakodkar et al. to decrease syndecan-1, an endothelial glycocalyx that contributes to mortality in septic patients
  • combined with hydrocortisone and thiamine, septic patients treated with 1.5 g of IV vitamin C every six hours showed a distinct decrease in their SOFA scores and none of the patients treated developed organ failure
  • combined with hydrocortisone and thiamine, septic patients treated with 1.5 g of IV vitamin C every six hours showed a distinct decrease in their SOFA scores and none of the patients treated developed organ failure
  • reduced overall mortality
  • reduced overall mortality
  • propose the use for high-dose vitamin C to aid in the treatment of septic shock-induced hypotension
  • treatment of severe sepsis using a high dose (up to 200 mg/kg/day) of IV vitamin C was explored in phase I, a double-blind, randomized, placebo-controlled trial by Fowler et al. [75]. Their findings included a reduction in SOFA scores and decreased vascular injury compared to a placebo control group, all while showing minimal adverse side effects
    • Nathan Goodyear
      Nathan Goodyear on 01 Sep 23
       
      High dose here is laughable. Again, duration and frequency also.
  • Maintaining a daily intake of 75 and 100 mg for men and women, respectively, as recommended by the U.S. Institute of Medicine
    • Nathan Goodyear
      Nathan Goodyear on 01 Sep 23
       
      This recommendation is FRANK IGNORANCE
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
croservices

Tech-Enabled Contract Research Organization | Vial CRO - 1 views

vial.com/cro

Health Healthcare CRO Contract Research Organization

shared by croservices on 08 Dec 22 - No Cached
croservices liked it
  • croservices on 08 Dec 22
     
    Vial is a technology enabled Contract Research Organization (CRO) that delivers faster, higher quality trial outcomes.
Nathan Goodyear

Immunotherapy in People with Cancer and Autoimmune Diseases - NCI - 0 views

www.cancer.gov/...immune-diseases-clinical-trial

autoimmune autoimmune disease disease cancer

shared by Nathan Goodyear on 04 Feb 23 - No Cached
  • Nathan Goodyear on 04 Feb 23
     
    Quote that 30% of cancer patients have coexisting autoimmune disease. No real reference for that percentage.
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