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Nathan Goodyear

Ascorbate in pharmacologic concentrations selectively generates ascorbate radical and h... - 0 views

www.ncbi.nlm.nih.gov/...PMC1885574

vitamin C ascorbic acid Cancer

shared by Nathan Goodyear on 05 Mar 18 - No Cached
  • Proposed mechanism
  • The data show that pharmacologic ascorbate concentrations produced Asc•− selectively in extracellular fluid compared with blood and that H2O2 formation occurred when Asc•− concentrations were >100 nM in extracellular fluid.
  • These data validate the hypothesis that ascorbate is a prodrug for selective delivery of reactive species to the extravascular space
  • ...22 more annotations...
  • pharmacologic ascorbate as a prooxidant drug for therapeutic use.
  • Recently we reported that pharmacologic ascorbic acid concentrations produced H2O2 concentrations of ≥25 μM, causing cancer cell death in vitro
  • We found that H2O2 concentrations generated in vivo were those that caused cancer cell death in vitro
  • When ascorbate was given parenterally, Asc•−, the product of a loss of one electron from ascorbate, was detected preferentially in extracellular fluid compared with blood
  • Asc•− generation in extracellular fluid depended on the ascorbate dose and the resulting concentrations
  • With i.v. administration of ascorbate, Asc•− concentrations were as much as 12-fold greater in extracellular fluid compared to blood and approached 250 nM
  • In blood, such Asc•− concentrations were never produced and were always <50 nM
  • These data are all consistent with the hypothesis that pharmacologic ascorbate concentrations in vivo serve as a prodrug for selective delivery of H2O2 to the extracellular space
  • After oral ingestion, control of intracellular and extracellular ascorbate concentrations is mediated by three mechanisms: intestinal absorption, tissue transport, and renal reabsorption
  • intestinal absorption, or bioavailability, declines at doses >200 mg
    • Nathan Goodyear
      Nathan Goodyear on 05 Mar 18
       
      significant limitation of gut absorption of vitamin C--at 200 mg po.
  • corresponding to plasma concentrations of ≈60 μM
    • Nathan Goodyear
      Nathan Goodyear on 05 Mar 18
       
      equates to 0.06 mM.  Max blood levels found with po AA dosing has been 0.22 mM
  • at approximately this concentration, the ascorbate tissue transporter SVCT2 approaches Vmax, and tissues appear to be saturated
    • Nathan Goodyear
      Nathan Goodyear on 05 Mar 18
       
      SVCT2 Rc in gut reach max binding.
  • also at ≈60 μM, renal reabsorption approaches saturation, and excess ascorbate is excreted in urine
  • Parenteral administration bypasses tight control
  • When tight control is bypassed, H2O2 forms in the extracellular space
  • in vivo validation of ascorbate as a prodrug for selective H2O2 formation
  • Temporarily bypassing tight control with parenteral administration of ascorbate allows H2O2 to form in discrete time periods only, decreasing likelihood of harm, and provides a pharmacologic basis for therapeutic use of i.v. ascorbate
  • H2O2 formation results in selective cytotoxicity
  • Tumor cells are killed with exposure to H2O2 for ≤30 min
  • In vitro, killing is mediated by H2O2 rather than Asc•−
  • In addition to cancer treatment, another potential therapeutic use is for treatment of infections. H2O2 concentrations of 25–50 μM are bacteriostatic
  • virally infected cells may also be candidates
  • Nathan Goodyear on 05 Mar 18
     
    follow up invivo study to previous study from 2005.  Here, the authors prove their hypothesis that ascorbate is a prodrug for delivery of H2O2.
Nathan Goodyear

Low-Dose Chemotherapy with Insulin (Insulin Potentiation Therapy) in Combination with H... - 0 views

www.ncbi.nlm.nih.gov/...PMC3357525

prostate cancer IPTLD low-dose chemotherapy cancer chemotherapy insulin potentiation therapy LDMC low-dose metronomic chemotherapy IPT

shared by Nathan Goodyear on 25 Jan 18 - No Cached
  • The method of insulin potentiation therapy was empirically invented in 1930 from Mexican doctor D. Perez Garsia
  • increases the permeability of cell membrane
  • influences the metabolic processes in human body with the increase of the regenerating processes
  • ...9 more annotations...
  • facilitates the transport of intra and extra cellular liquids which helps the organism to eliminate the toxic products
  • The increased number of insulin receptors on the tumor cell, in comparison to the normal one, allows the before mentioned 2 factors to act predominantly
  • Increased permeability after the insulin effect on the cellular membrane results in increased intracellular quantity of antitumor agents
  • have other endocrine effects: directly stimulates suprarenal gland to produce epinephrine and glucocorticoid hormones and stimulates ACTH secretion. These endocrine effects also have a positive influence on the regenerating processes
  • Insulin influences the intracellular metabolism of the tumor cell, which leads to increase of the number of cells in phase S, where they are with highly sensitive to specific chemotherapeutics.
  • After the first 6 IPT applications overall (groups A and B) response to treatment on PSA criteria shows partial effect and stabilization in 12 of 16 (75%) patients
  • After the 10th IPTLD application or 3 months after starting treatment, complete response, partial response, and stabilization were observed in 4 of 9 (66.6%), while in 3 of 9 (33.3%) was registered complete effect
  • the advanced stage of disease in patients treated
  • Quality of life after the second IPTLD application is significantly improved
  • Nathan Goodyear on 25 Jan 18
     
    IPT found to be effextive in treated castrate-resistant prostate cancer.
umar111

Dolce & Gabbana The only one - PlazzaPK - 0 views

plazza.pk/...dolce-gabbana-the-only-one

dolce gabbana the one dolce and gabbana perfume dolce gabbana perfume the one dolce and gabbana the only one the one perfume perfume scent gabbana dolce dolce in gabbana

shared by umar111 on 30 Mar 23 - No Cached
  • umar111 on 30 Mar 23
     
    Dolce & Gabbana The Only One If you really love a female perfume to wear then don't miss this perfume by D&G The Only One. On your daily walks or just about anywhere else or with friends they have the perfect scent of sensuality.
umar111

Sauvage Dior Perfume - PlazzaPK - 0 views

plazza.pk/...sauvage-dior-perfume

sauvage dior perfume sauvage perfume sauvage perfume price sauvage dior perfume price dior sauvage 100ml price sauvage eau de perfume diorsauvage parfum

shared by umar111 on 30 Mar 23 - No Cached
  • umar111 on 30 Mar 23
     
    Sauvage Eau de Perfume, François Demarche, Dior Perfumer-Creator, drew inspiration from the desert at the magical
umar111

DC 24 Pure Perfume - PlazzaPK - 0 views

plazza.pk/...dc-24-pure-perfume

DC 24 Pure Perfume in Pakistan Lahore

shared by umar111 on 30 Mar 23 - No Cached
  • umar111 on 30 Mar 23
     
    Men Fragrance Type: Eau de Toilette Size: 100ml Fragrance Family: Floral & Fruity Perfume name: 24 Pure
umar111

A*Men Mugler Perfume - PlazzaPK - 0 views

plazza.pk/...amen-mugler-perfume

a men perfume mugler paris in Pakistan fragrance

shared by umar111 on 30 Mar 23 - No Cached
  • umar111 on 30 Mar 23
     
    A*Men Mugler Paris Perfume A*Men Mugler Perfume the first male fragrance created by MUGLER, materializes the contemporary hero, a man who imposes himself by his inner strength, and his desire to win.
goodbfoods

Immerse Yourself in Nature's Sweet Symphony with GOODB White Honey - 1 views

goodb.in/...white-honey-500gm

HONEY PURE RAW

shared by goodbfoods on 20 Feb 24 - No Cached
  • goodbfoods on 20 Feb 24
     
    Dive into the extraordinary world of natural sweetness with GOODB Premium White Honey - a harmonious blend of raw and pure honey, crafted to perfection.
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