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Nathan Goodyear

Testosterone, thrombophilia, throm... [Blood Coagul Fibrinolysis. 2014] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...24732175

Testosterone therapy men male hormones hormone thrombophilia thrombosis clotting

shared by Nathan Goodyear on 16 Apr 14 - No Cached
  • Nathan Goodyear on 16 Apr 14
     
    This study's conclusion is to evaluate clotting factor i.e. factor V leiden, Factor VIII, and prothrombin prior to giving Testosterone.  This small study found increased clotting in some men on Testosterone. The problem here is the dosing of Testosterone in these men was 50-160 mg.  Physiologic dosing is 5-10 mg.  The problem is doping.  One wonders if physiologic dosing was undertaken if any of the men in this study would develop clotting problems, even though they had undiagnosed hypercoagulabitliy.
Nathan Goodyear

High dose intravenous vitamin c and metastatic pancreatic cancer: Two cases - 0 views

www.oatext.com/ancreatic-cancer-Two-cases.php

pancreatic cancer cancer IV vitamin c vitamin c alternative cancer treatment alternative medicine

shared by Nathan Goodyear on 31 Jan 18 - No Cached
  • Nathan Goodyear on 31 Jan 18
     
    2 case studies of high dose vitamin C in pancreatic cancer with good results.  The important thing here is the imaging and biomarkers were initiated and followed.  Progressive cancers, like pancreatic cancer, require more frequent dosing of IVC.
Nathan Goodyear

Vitamin C increases viral mimicry induced by 5-aza-2′-deoxycytidine | PNAS - 0 views

www.pnas.org/10238

AML leukemia acute myeloid leukemia MDS vitamin C cancer

shared by Nathan Goodyear on 12 May 18 - No Cached
  • Vitamin C alone at concentrations up to 57 μM had little effect on cell growth but was toxic at 228 μM (SI Appendix, Fig. S1B), in line with recent studies of high vitamin C concentrations (125–2,000 μM)
  • In our combination approach, vitamin C increased the effects of low doses of 5-aza-CdR, with 57 μM vitamin C almost doubling the growth inhibition
  • Using the Chou–Talalay method (28), we found that the two compounds indeed acted synergistically, rather than additively, to inhibit cancer cell growth over the physiological ranges of vitamin C in healthy individuals (26–84 μM)
  • ...12 more annotations...
  • These results show that targeting the cancer DNA methylome by combining low-dose 5-aza-CdR and vitamin C stimulates the expression of ERVs, the induction of a cell-autonomous immune activation response, and increased apoptosis of cancer cells
  • The addition of vitamin C to treatment protocols therefore may be a straightforward way to increase the clinical efficacy of such drugs in MDS and leukemia patients
  • Vitamin C deficiency has been seen previously in patients with multiple types of cancer, including hematological malignancies (35⇓–37). We predict that these patients might receive the most benefits from the combination treatment.
  • induction of an innate immune response
  • We therefore measured plasma concentrations of vitamin C in a small number of patients with miscellaneous hematologic malignancies. Strikingly, 58% of patients with hematological neoplasia who were not taking vitamin C supplements had severe vitamin C deficiency (serum concentration <11.4 μM, at which clinical features of scurvy may be manifested) (34), and 33% had vitamin C levels below the normal range
  • it is possible that vitamin C was oxidized to DHA before it was transported into the cells
  • Oral administration of vitamin C should be sufficient for the therapeutic strategy, because the concentrations reported in this study would not require i.v. administration.
    • Nathan Goodyear
      Nathan Goodyear on 12 May 18
       
      This statement lacks a basic understanding of vitamin C pharmacokinetics.
  • Vitamin C is an essential nutrient for humans and has been reported to increase IFN levels in human cells upon virus infection
  • daily treatment with vitamin C alone at physiological concentrations enhanced the expression of viral-defense genes relative to untreated cells
  • When combined with low-dose 5-aza-CdR, physiological concentrations of vitamin C synergistically inhibited cancer-cell growth and induced apoptosis. Such synergy was associated with increased ERV expression and dsRNA in treated cells. The mechanism of action differs from that of vitamin C at higher doses, which involves its pro-oxidant activity, including GSH inhibition, to generate reactive oxygen species
  • This activity has been shown to induce DNA damage and to enhance the sensitivities of myeloid malignancies, multiple myeloma, and cutaneous T-cell lymphoma to arsenic trioxide (41⇓⇓–44). It also can increase chemosensitivity of ovarian cancer cells (27) and selectively kill KRAS or BRAF mutant colorectal cancer cells by inhibiting GAPDH
  • reactive oxygen species
  • Nathan Goodyear on 12 May 18
     
    91% of patients with hematologic malignancies have vitamin C levels that are either low or severly deficient. This study found that vitamin C plus low dose DNA methyltransferase inhibitors have synergistic inhibition of cancer cell proliferation and increased apoptosis.  Unfortunately, the authors claimed that oral vitamin C would be sufficient which indicates an incredible lack of understanding of vitamin C pharmacokinetics.
Nathan Goodyear

Opposing effects of low versus high concentrations of water soluble vitamins/dietary in... - 0 views

www.ncbi.nlm.nih.gov/...28755485

vitamin C cancer colorectal cancer niacin

shared by Nathan Goodyear on 18 Aug 19 - No Cached
  • Nathan Goodyear on 18 Aug 19
     
    High dose vitamin C + high dose niacin kill CSCs, but low dose stimulates CSCs.
Nathan Goodyear

Low-dose Interleukin-2 in the Treatment of Autoimmune Disease | touchONCOLOGY - 0 views

www.touchoncology.com/...2-treatment-autoimmune-disease

cancer autoimmune disease Tregs Treg cells Treg immune system disease IL-2

shared by Nathan Goodyear on 04 Apr 18 - No Cached
Amol kashikar liked it
  • affect approximately 5 to 8 % of the US population
  • the incidence and prevalence of autoimmune diseases are rising
  • Type 1 diabetes (T1D), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and inflammatory bowel disease (IBD) account for the majority of the patients with autoimmune diseases
  • ...9 more annotations...
  • Autoimmune diseases are characterized by a breakdown of mechanisms that allow the immune system to distinguish between self and nonself and maintain immunologic self-tolerance
  • Tregs, which are important in the maintenance of peripheral immune tolerance.
  • Several subtypes of Tregs exist, the most well studied being CD4+ cells that express high-level CD25 and the transcription factor forkhead box P3 (FOXP3)
  • Treg deficiency or dysfunction is associated with autoimmune disease
  • In clinical studies, decreased levels of circulating CD25+CD4+ T cells have been reported in patients with autoimmune disease
  • These data have led to the hypothesis that augmentation of Tregs may be a useful therapeutic strategy in autoimmune disease
  • Treg augmentation has resulted in clinical improvements in numerous animal models of autoimmune diseases
  • the administration of in vitro expanded CD4+CD25highCD127-Tregs has been found to be safe and may help to preserve β-cell function in children with T1D
  • ability of IL-2 to augment the numbers and function of CD4+ Tregs.
  • Nathan Goodyear on 04 Apr 18
     
    Great article.  Immune dysfunction plays role in autoimmune disease and cancer.  Treg cells sit at the center of autoimmunity.  This artice highlights the different uses: low dose IL2 therapy to augment Tregs and reduce autoinflammation and high dose IL2 to augment Treg cells in the fight against cancer.
Nathan Goodyear

High-Dose Vitamin C for Cancer Therapy - PMC - 0 views

www.ncbi.nlm.nih.gov/...PMC9231292

vitamin C cancer

shared by Nathan Goodyear on 27 Jul 22 - No Cached
  • diabetes [8], atherosclerosis [9], the common cold [10], cataracts [11], glaucoma [12], macular degeneration [13], stroke [14], heart disease [15], COVID-19 [16], and cancer.
  • 1–5% of the Vit-C inside the human cells
  • interaction between Fe(II) and H2O2 produces OH− through the Fenton reaction
  • ...35 more annotations...
  • metabolic activity, oxygen transport, and DNA synthesis
  • Iron is found in the human body in the form of haemoglobin in red blood cells and growing erythroid cells.
  • macrophages contain considerable quantities of iron
  • iron is taken up by the majority of cells in the form of a transferrin (Tf)-Fe(III) complex that binds to the cell surface receptor transferrin receptor 1 (TfR1)
  • excess iron is retained in the liver cells
  • the endosomal six transmembrane epithelial antigen of the prostate 3 (STEAP3) reduces Fe(III) (ferric ion) to Fe(II) (ferrous ion), which is subsequently transferred across the endosomal membrane by divalent metal transporter 1 (DMT1)
  • labile iron pool (LIP)
  • LIP is toxic to the cells owing to the production of massive amounts of ROS.
  • DHA is quickly converted to Vit-C within the cell, by interacting with reduced glutathione (GSH) [45,46,47]. NADPH then recycles the oxidized glutathione (glutathione disulfide (GSSG)) and converts it back into GSH
  • Fe(II) catalyzes the formation of OH• and OH− during the interaction between H2O2 and O2•− (Haber–Weiss reaction)
  • Ascorbate can efficiently reduce free iron, thus recycling the cellular Fe(II)/Fe(III) to produce more OH• from H2O2 than can be generated during the Fenton reaction, which ultimately leads to lipid, protein, and DNA oxidation
  • Vit-C-stimulated iron absorption
  • reduce cellular iron efflux
  • high-dose Vit-C may elevate cellular LIP concentrations
  • ascorbate enhanced cancer cell LIP specifically by generating H2O2
  • Vit-C produces H2O2 extracellularly, which in turn inhibits tumor cells immediately
  • tumor cells have a need for readily available Fe(II) to survive and proliferate.
  • Tf has been recognized to sequester most labile Fe(II) in vivo
  • Asc•− and H2O2 were generated in vivo upon i.v Vit-C administration of around 0.5 g/kg of body weight and that the generation was Vit-C-dose reliant
  • free irons, especially Fe(II), increase Vit-C autoxidation, leading to H2O2 production
  • iron metabolism is altered in malignancies
  • increase in the expression of various iron-intake pathways or the downregulation of iron exporter proteins and storage pathways
  • Fe(II) ion in breast cancer cells is almost double that in normal breast tissues
  • macrophages in the cancer microenvironment have been revealed to increase iron shedding
  • Advanced breast tumor patients had substantially greater Fe(II) levels in their blood than the control groups without the disease
  • increased the amount of LIP inside the cells through transferrin receptor (TfR)
  • Warburg effect, or metabolic reprogramming,
  • Warburg effect is aided by KRAS or BRAF mutations
  • Vit-C is supplied, it oxidizes to DHA, and then is readily transported by GLUT-1 in mutant cells of KRAS or BRAF competing with glucose [46]. DHA is quickly converted into ascorbate inside the cell by NADPH and GSH [46,107]. This decrease reduces the concentration of cytosolic antioxidants and raises the intracellular ROS amounts
  • increased ROS inactivates glyceraldehyde 3-phosphate dehydrogenase (GAPDH)
  • ROS activates poly (ADP-ribose) polymerase (PARP), which depletes NAD+ (a critical co-factor of GAPDH); thus, further reducing the GAPDH associated with a multifaceted metabolic rewiring
  • Hindering GAPDH can result in an “energy crisis”, due to the decrease in ATP production
  • high-dose Vit-C recruited metabolites and increased the enzymatic activity in the pentose phosphate pathway (PPP), blocked the tri-carboxylic acid (TCA) cycle, and increased oxygen uptake, disrupting the intracellular metabolic balance and resulting in irreversible cell death, due to an energy crisis
  • mega-dose Vit-C influences energy metabolism by producing tremendous amounts of H2O2
  • Due to its great volatility at neutral pH [76], bolus therapy with mega-dose DHA has only transitory effects on tumor cells, both in vitro and in vivo.
Nathan Goodyear

Cellular toxicity driven by high-dose vitamin C on normal and cancer stem cells - PubMed - 0 views

pubmed.ncbi.nlm.nih.gov/29432735

IV vitamin C CSC High dose IV vitamin C cancer stem cells vitamin C high dose vitamin C high-dose IV vitamin C cancer

shared by Nathan Goodyear on 03 Sep 22 - No Cached
  • Nathan Goodyear on 03 Sep 22
     
    High dose vitamin C preferentially targets CSC but not differentiated cells.
Nathan Goodyear

Temperature-dependent and time-dependent effects of hyperthermia mediated by dextran-co... - 0 views

www.ncbi.nlm.nih.gov/...PMC4346362

hyperthermia

shared by Nathan Goodyear on 18 Apr 23 - No Cached
  • Nathan Goodyear on 18 Apr 23
     
    effect of time and temperature on the viability of melanoma cell lines and expression of HSP 70 & 90 after brief exposure to hyperthermia. While hyperthermia has multiple mechanisms of action, this paper elucidates two essential benefits of high-dose hyperthermia. First, the study illustrates why high-dose hyperthermia treatments (45°C - 47°C) are so much more effective than the low-dose hyperthermia (39°C - 43°C) produced by commercially available heating devices.
Nathan Goodyear

Low-dose naltrexone targets the opioid growth factor-opioid growth factor receptor path... - 0 views

ebm.rsmjournals.com/...1036.full

low dose naltrexone LND low dose naltrexone cancer cell proliferation opioid growth factor OGF

shared by Nathan Goodyear on 27 Nov 12 - No Cached
  • Nathan Goodyear on 27 Nov 12
     
    low-dose naltrexone (NLD) is shown to inhibit growth in vivo.  This is important as it has implications in cancer therapies.  This study found a greater benefit with LDN and exogenous opioid growth factor (OGF).
Nathan Goodyear

Pharmacologic doses of ascorbate act as a prooxidant and decrease growth of aggressive ... - 0 views

www.pnas.org/...11105.full

IV vitamin C vitamin C ovarian cancer pancreatic cancer glioblastoma cancer

shared by Nathan Goodyear on 26 May 13 - Cached
  • Nathan Goodyear on 26 May 13
     
    high dose IV vitamin C shown to be treatment option in Cancer.  Granted in a mouse study, but high dose IV vitamin C shown to decrease growth rates of ovarian, pancreatic, and glioblastoma cancers.
Nathan Goodyear

Massive Doses of Vitamin C and the Virus Diseases - 0 views

www.seanet.com/...med_surg-1951-v103-n4-p101.htm

IV therapy IV C virus viral illness nutrition nutritional therapy

shared by Nathan Goodyear on 23 Jan 13 - No Cached
  • Nathan Goodyear on 23 Jan 13
     
    High dose IV vitamin C beneficial in viral illnesses.  This is a case study article, but it discusses how viral illnesses are associated with low vitamin C levels and how high dose vitamin C therapy benefits the immune activity against viral invaders.
Nathan Goodyear

Favorable Outcome After Physiologic Dose of Sodium-d,l-3-Hydroxybutyrate in Severe MADD... - 0 views

pediatrics.aappublications.org/...e1224.long

ketones ketone bodies ketone salts

shared by Nathan Goodyear on 21 Nov 16 - No Cached
  • Nathan Goodyear on 21 Nov 16
     
    high dose of ketone therapy via 3-HB ketone salt, in this case study, tolerated fine.  Most important, the higher, physiologic dose provided clinical improvement.
Nathan Goodyear

High doses of vitamin E in the treatment of disorders of the central nervous system in ... - 0 views

ajcn.nutrition.org/...793.full

vitamin E Parkinson's disease Parkinson's alzheimer's disease Alzheimers alternative medicine

shared by Nathan Goodyear on 13 Jun 16 - No Cached
  • Nathan Goodyear on 13 Jun 16
     
    High dose vitamin E, in doses up to 2,000 IU, in patients with Parkinson, Alzheimers and tar dive dyskinesia found to be safe and somewhat effective in these disease states in older individuals.  The length of the studies reviewed were up to 2 years.
Nathan Goodyear

Bisphenol A Promotes Human Prostate Stem-Progenitor Cell Self-Renewal and Increases In ... - 0 views

www.ncbi.nlm.nih.gov/...PMC3929731

BPA bisphenol A cancer prostate cancer prostate xenoestrogens

shared by Nathan Goodyear on 20 Apr 16 - No Cached
  • these findings show that estrogen stimulates human prostate epithelial stem cell self-renewal and progenitor cell amplification (prostasphere size), with the greatest effects observed at lower E2 doses.
  • Similar to E2, BPA increased prostasphere number and size with significant and maximal effects observed at 10 nM BPA
  • Taken together, these results provide strong evidence that, similar to E2, BPA increases stem cell self-renewal and progenitor amplification in normal human prostate epithelial cells
  • ...13 more annotations...
  • these findings provide further support that E2 and BPA maintain the stem-like state within the normal prostate epithelial cell population
  • Our previous findings demonstrated that normal prostate stem-progenitor cells within the prostaspheres expressed ERα and ERβ, implicating them as direct targets for E2 and BPA action
  • p-Akt and p-Erk, well established downstream targets of membrane-associated ERs
  • BPA and E2 had equimolar capacity for activation of these rapid signaling pathways in human prostaspheres, thus identifying a dynamic and robust signaling pathway initiated by low-dose BPA exposure in prostate stem-progenitor cells.
  • these findings indicate that both rapid membrane-initiated estrogen action and genomic ER signaling pathways are operative in human prostate progenitor cells.
  • these results document the fact that levels of bioactive BPA in the present study are similar to levels found in human umbilical cord blood and newborns in the general population
  • the present findings identify for the first time that in vivo exposure of the human prostate epithelium to low doses of BPA significantly increases the susceptibility of the human prostate epithelium to hormonal carcinogenesis.
  • The current study provides clear evidence that, similar to E2, normal human prostate stem and progenitor cells are direct targets for BPA action
  • Both hormones increased stem-like cell numbers in primary prostate epithelial cultures in a dose-dependent manner and augmented the number and size of 3-D cultured prostaspheres, markers of stem cell self-renewal and progenitor cell proliferation, respectively
  • signaling pathways engaged by estrogens through these separate receptors are multiple and complex, including both membrane-initiated signaling and genomic activation via ER transcriptional activity
  • Estrogen action is mediated by ERα and ERβ
  • the current results indicate that developmental exposure to BPA, at doses routinely found in humans, significantly increases the cancer risk in human prostate epithelium in response to elevated estrogen levels in an androgen-supported milieu. Because relative estrogen levels rise in aging men, we suggest that humans may be susceptible to BPA-driven prostate disease in a manner similar to that in the rodent models.
  • We propose that early-life perturbations in estrogen signaling including inappropriate exposure to BPA have the potential to amplify and modify the stem-progenitor cell populations within the human prostate gland and, in so doing, alter the normal homeostatic mechanisms that maintain a growth neutral state throughout life
  • Nathan Goodyear on 20 Apr 16
     
    Bisphenol A exposure in utero found to increase prostate cancer risk later in life.  This exposure occurred at typical life exposure levels as found in umbilical cord blood sampling,  This occurred through stem cell self-renewal and progenitor amplification
Nathan Goodyear

Low-dose hydrocortisone in chronic fatigue syndrome: a randomised crossover trial : The... - 0 views

www.thelancet.com/...fulltext

CFS chronic fatigue syndrome hydrocortisone cortisol fatigue adrenal fatigue hypoadrenia adrenal insufficiency

shared by Nathan Goodyear on 01 May 12 - No Cached
  • Nathan Goodyear on 01 May 12
     
    low dose hydrocortisone therapy, 5-10 mg, shown to be effective short-term therapy in patients with chronic fatigue syndrome.  Additionally, and very important, this study found no adrenal function suppression at these doses.
Nathan Goodyear

Safety and immunologic effects of high- vs low-dose cholecalciferol in multiple sclerosis - 0 views

www.neurology.org/...382

vitamin D MS multiple Sclerosis inflammation IL-17

shared by Nathan Goodyear on 25 Feb 16 - No Cached
  • Nathan Goodyear on 25 Feb 16
     
    High dose vitamin D (10,400 IU) found to reduce IL-17, CD161 and effector memory cells; in contrast low dose vitamin D (800 IU)  did not.  The study also called into question the traditional target range of vitamin D.  The authors here proposed 40-60
Nathan Goodyear

Safety and immunologic effects of high- vs low-dose cholecalciferol in multiple sclerosis - 0 views

www.neurology.org/...WNL.0000000000002316

multiple Sclerosis MS vitamin D inflammation IL-17

shared by Nathan Goodyear on 07 Jan 16 - No Cached
  • Nathan Goodyear on 07 Jan 16
     
    Not only is high dose vitamin D3 therapy more effective in reducing IL-17 compared to low dose, but it is safe to in individuals with MS.  The hot topic these days is immunotherapy: that is exactly what vitamin D therapy is.
Nathan Goodyear

Nivolumab for previously treated unresectable metastatic anal cancer (NCI9673): a multi... - 0 views

www.ncbi.nlm.nih.gov/...PMC5809128

cancer anal cancer nivolumab immunotherapy

shared by Nathan Goodyear on 13 Jul 18 - No Cached
  • Patients received a median of six doses of nivolumab
  • four of the first 12 patients had partial responses
  • Nine (24% [95% CI 15–33]) of 37 patients achieved a response (seven partial responses and two complete responses
  • ...16 more annotations...
  • no treatment-related deaths
  • the most common adverse events were anaemia (26 [70%]), fatigue (25 [68%]), and rash
  • hypothyroidism
  • hypothyroidism
  • nivolumab-related autoimmune hypothyroidism, which resolved after a short course of corticosteroids
  • No grade 3 or 4 adverse events occurred
  • Nivolumab resulted in objective responses in 24% of patients with metastatic SCCA
  • Historically, doublet chemotherapy with cisplatin and fluorouracil has been the most common treatment for patients with metastatic SCCA
  • our results suggest that immune checkpoint blockade agents might extend overall survival beyond currently available therapies, especially if provided early in the disease treatment course
  • the dose of nivolumab we used differs from the 2016 recommendation of a fixed 240 mg every 2 weeks
  • 25% of patients develop distant metastases
  • most patients with localised SCCA are cured by chemoradiation
  • More than 90% of cases of SCCA are linked to prior infection with human papillomavirus (HPV)
  • Within tumour cells, HPV oncoproteins are immunogenic and can trigger an anti-tumour host immune response by recruitment of tumour-infiltrating lymphocytes
  • Tumour cells express PD-L1 and, on binding its inhibitory receptor PD-1 on the surface of T cells, downregulate T-cell activation and thwart the local anti-tumour immune response
  • Nivolumab is a humanised monoclonal antibody against PD-1 that disrupts this interaction, enabling T-cell cytotoxicity. It has activity as a monotherapy in advanced solid cancers, such as head and neck cancer, melanoma, non-small-cell lung cancer, and renal cell carcinoma
  • Nathan Goodyear on 13 Jul 18
     
    study finds nivolumab helpful in some patients with surgically unresectable or metastatic anal cancer.  The dose used was 3 mg/kg every 2 weeks. 
Nathan Goodyear

Safety, tolerability, and pharmacokinetics of escalating high doses of ivermectin in he... - 0 views

www.ncbi.nlm.nih.gov/...12362927

ivermectin cancer

shared by Nathan Goodyear on 16 Apr 18 - No Cached
  • Nathan Goodyear on 16 Apr 18
     
    Ivermectin safe without significant side effects, including CNS toxicity, in doses 10x 200 mcg/kg (highest FDA approved dose).
Nathan Goodyear

Phase I study of high-dose ascorbic acid with mFOLFOX6 or FOLFIRI in patients with meta... - 0 views

www.ncbi.nlm.nih.gov/...PMC6524297

cancer IV vitamin C vitamin C

shared by Nathan Goodyear on 30 Jul 19 - No Cached
  • Nathan Goodyear on 30 Jul 19
     
    IV vitamin C shown to be adjunctive with the chemotherapy regimens FOLFIRI and FOLFOX in colorectal and gastric cancer despite the therapeutic dose limited to 1.5 mg/kg/day, which is a low dose likely resulting in sub-therapeutic levels.
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