Skip to main content

Home/ Dr. Goodyear/ Group items tagged dosing

Rss Feed Group items tagged

Filter: All | Bookmarks | Topics Simple Middle
Nathan Goodyear

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

www.ebiomedicine.com/...fulltext

multiple myeloma vitamin C IV vitamin C smoldering myeloma cancer

shared by Nathan Goodyear on 25 Sep 17 - No Cached
  • 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., 2008Chen et al., 2008), in xenograft MM mice
  • ...33 more annotations...
  • 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. 3Fig. 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
  • Nathan Goodyear on 25 Sep 17
     
    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

The Role of Vitamin C in Human Immunity and Its Treatment Potential Against COVID-19: A... - 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
pharmacybiz

Covid-19 : Over 40M People Are Double Jabbed - 0 views

www.pharmacy.biz/double-jabbed-against-covid-19

NHS-Covid-19-vaccination-programme pharmacy-business recent-pharmacy-news-uk 40-million-second-doses uk-second-dose-vaccine-percentage

shared by pharmacybiz on 13 Jan 22 - No Cached
  • pharmacybiz on 13 Jan 22
     
    The NHS Covid-19 vaccination programme has administered more than 40 million second doses following a bumper week that saw over 200,000 people coming forward for their second jab. Last week, more than 65,000 people aged 18 and over also stepped up to get their first dose of the Covid-19 jab. The NHS continued to encourage people to come forward for their first, second or third doses. Recent data from the UK Health Security Agency (UKHSA) showed that two doses of the vaccine are not enough to avoid the Omicron infection, but a booster significantly increases protection against the variant. Since the start of vaccination programme, NHS England has administered more than 113 million jabs in total. However, more than 1.1 million people aged 18 and over have still not come forward for their second dose.
Nathan Goodyear

High-dose vitamin C therapy for inclusion body myositis. - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...11411094

vitamin C IV vitamin C myositis autoimmune disease intravenous vitamin C inflammation

shared by Nathan Goodyear on 17 Aug 17 - No Cached
  • Nathan Goodyear on 17 Aug 17
     
    study finds "high dose" IV vitamin C benefited 3 of 5 patients in short 4 week study.  The "high dose" was not high dose at all, so that fact that a low dose of IV vitamin C will benefit dermatomysotis in over 50% of the patients in this very small study points to the question, what if actually high dose vitamin C is used.
Nathan Goodyear

Vitamin C preferentially kills cancer stem cells in hepatocellular carcinoma via SVCT-2... - 0 views

www.nature.com/...s41698-017-0044-8

cancer cancer stem cells liver cancer vitamin C IV vitamin C oncology

shared by Nathan Goodyear on 30 Jan 18 - No Cached
  • Chen et al. have revealed that ascorbate at pharmacologic concentrations (0.3–20 mM) achieved only by intravenously (i.v.) administration selectively kills a variety of cancer cell lines in vitro, but has little cytotoxic effect on normal cells.
  • Ascorbic acid (the reduced form of vitamin C) is specifically transported into cells by sodium-dependent vitamin C transporters (SVCTs)
  • SVCT-1 is predominantly expressed in epithelial tissues
  • ...41 more annotations...
  • whereas the expression of SVCT-2 is ubiquitous
  • differential sensitivity to VC may result from variations in VC flow into cells, which is dependent on SVCT-2 expression.
  • high-dose VC significantly impaired both the tumorspheres initiation (Fig. 4d, e) and the growth of established tumorspheres derived from HCC cells (Fig. 4f, g) in a time-dependent and dose-dependent manner.
  • Hepatocellular carcinoma (HCC)
  • The antioxidant, N-acetyl-L-cysteine (NAC), preventing VC-induced ROS production (a ROS scavenger), completely restored the viability and colony formation among VC-treated cells
  • DNA double-strand damage was found following VC treatment
  • DNA damage was prevented by NAC
  • Interestingly, the combination of VC and cisplatin was even more effective in reducing tumor growth and weight
  • Consistent with the in vitro results, stemness-related genes expressions in tumor xenograft were remarkably reduced after VC or VC+cisplatin treatment, whereas conventional cisplatin therapy alone led to the increase of CSCs
  • VC is one of the numerous common hepatoprotectants.
  • Interestingly, at extracellular concentrations greater than 1 mM, VC induces strong cytotoxicity to cancer cells including liver cancer cells
  • we hypothesized that intravenous VC might reduce the risk of recurrence in HCC patients after curative liver resection.
  • Intriguingly, the 5-year disease-free survival (DFS) for patients who received intravenous VC was 24%, as opposed to 15% for no intravenous VC-treated patients
  • Median DFS time for VC users was 25.2 vs. 18 months for VC non-users
  • intravenous VC use is linked to improved DFS in HCC patients.
  • In this study, based on the elevated expression of SVCT-2, which is responsible for VC uptake, in liver CSCs, we revealed that clinically achievable concentrations of VC preferentially eradicated liver CSCs in vitro and in vivo
    • Nathan Goodyear
      Nathan Goodyear on 31 Jan 18
       
      the authors here made similar mistakes to the Mayo authors i.e. under doses here in this study.  They dosed at only 2 grams IVC.  A woefully low dose of IVC.
  • Additionally, we found that intravenous VC reduced the risk of post-surgical HCC progression in a retrospective cohort study.
    • Nathan Goodyear
      Nathan Goodyear on 31 Jan 18
       
      positive results despite a low dose used.
    • Nathan Goodyear
      Nathan Goodyear on 31 Jan 18
       
      Their comfort zone was 1mM.  They should have targeted 20-40 mM.
  • Three hundred thirty-nine participants (55.3%) received 2 g intravenous VC for 4 or more days after initial hepatectomy
  • As the key protein responsible for VC uptake in the liver, SVCT-2 played crucial roles in regulating the sensitivity to ascorbate-induced cytotoxicity
  • we also observed that SVCT-2 was highly expressed in human HCC samples and preferentially elevated in liver CSCs
  • SVCT-2 might serve as a potential CSC marker and therapeutic target in HCC
  • CSCs play critical roles in regulating tumor initiation, relapse, and chemoresistance
  • we revealed that VC treatment dramatically reduced the self-renewal ability, expression levels of CSC-associated genes, and percentages of CSCs in HCC, indicating that CSCs were more susceptible to VC-induced cell death
  • as a drug for eradicating CSCs, VC may represent a promising strategy for treatment of HCC, alone or particularly in combination with chemotherapeutic drugs
  • In HCC, we found that VC-generated ROS caused genotoxic stress (DNA damage) and metabolic stress (ATP depletion), which further activated the cyclin-dependent kinase inhibitor p21, leading to G2/M phase cell cycle arrest and caspase-dependent apoptosis in HCC cells
  • we demonstrated a synergistic effect of VC and chemotherapeutic drug cisplatin on killing HCC both in vitro and in vivo
  • Intravenous VC has also been reported to reduce chemotherapy-associated toxicity of carboplatin and paclitaxel in patients,38 but the specific mechanism needs further investigation
    • Nathan Goodyear
      Nathan Goodyear on 31 Jan 18
       
      so, exclude the benefit to patients until the exact mechanism of action, which will never be fully elicited?!?!?
  • Our retrospective cohort study also showed that intravenous VC use (2 g) was related to the improved DFS in HCC patients after initial hepatectomy
    • Nathan Goodyear
      Nathan Goodyear on 31 Jan 18
       
      Terribly inadequate dose.  Target is 20-40 mM which other studies have found occur with 50-75 grams of IVC.
  • several clinical trials of high-dose intravenous VC have been conducted in patients with advanced cancer and have revealed improved quality of life and prolonged OS
  • high-dose VC was not toxic to immune cells and major immune cell subpopulations in vivo
  • high recurrence rate and heterogeneity
  • tumor progression, metastasis, and chemotherapy-resistance
  • SVCT-2 was highly expressed in HCC samples in comparison to peri-tumor tissues
  • high expression (grade 2+/3+) of SVCT-2 was in agreement with poorer overall survival (OS) of HCC patients (Fig. 1c) and more aggressive tumor behavior
  • SVCT-2 is enriched in liver CSCs
  • these data suggest that SVCT-2 is preferentially expressed in liver CSCs and is required for the maintenance of liver CSCs.
  • pharmacologic concentrations of plasma VC higher than 0.3 mM are achievable only from i.v. administration
  • The viabilities of HCC cells were dramatically decreased after exposure to VC in dose-dependent manner
  • VC and cisplatin combination further caused cell apoptosis in tumor xenograft
  • These results verify that VC inhibits tumor growth in HCC PDX models and SVCT-2 expression level is associated with VC response
  • qPCR and IHC analysis demonstrated that expression levels of CSC-associated genes and percentages of CSCs in PDXs dramatically declined after VC treatment, confirming the inhibitory role of VC in liver CSCs
  • Nathan Goodyear on 30 Jan 18
     
    IV vitamin C in vitro and in vivo found to "preferentially" eradicate cancer stem cells.  In addition, IV vitamin C was found to be adjunctive to chemotherapy, found to be hepatoprotectant.  This study also looked at SVCT-2, which is the transport protein important in liver C uptake.
Nathan Goodyear

Interleukin‐2 enhances the natural killer cell response to Herceptin‐coated H... - 1 views

onlinelibrary.wiley.com/...%3AAID-IMMU3016%3E3.0.CO%3B2-J

IL-2 breast cancer cancer NK cells HER-2 immunotherapy

shared by Nathan Goodyear on 18 Jun 18 - No Cached
  • administration of low‐dose IL‐2 results in expansion of a CD3– / CD56+ NK cell population in patients with advanced cancer
  • approximately 20 % will overexpress theHer2 / neu proto‐oncogene
  • In breast cancer, Her2 / neu overexpression is associated with a worse histologicalgrade, decreased relapse‐free and overall survival periods, and altered sensitivity to chemotherapeutic regimens
  • ...17 more annotations...
  • NK cells are large granular lymphocytes that comprise approximately 10 % of circulating lymphocytes
  • all human NK cells express the CD56 antigen
  • treatment with various concentrations of IL‐2 in vivo may induce distinct functions within the NK cell compartment and, therefore, may have profound effects on NK cell‐mediated cytotoxicity
  • CD56bright
  • CD56dim
  • We show here that ADCC conducted by NK cells in vitro is enhanced by IL‐2 activation and is critically dependent on interactions between FcγRIII on NK cells and Herceptin‐coated tumor targets
  • administration of low‐dose IL‐2 to patients results in the marked expansion of a CD56+ population of immune effectors with the ability to lyse antibody‐coated cancer targets
  • NK cells represented only 7 % of lymphocytes prior to therapy but comprised over 50 % of the population after 10 weeks of low‐dose IL‐2
  • These data suggest that the enhanced ADCC seen following the expansion of NK cells with low‐dose IL‐2 is likely due to an increase in the overall number of NK cells
  • co‐administration of IL‐2 with rhu4D5 mAb will enhance activation of NK cell effector functions
  • Stimulation of NK cells with IL‐2 resulted in a significant increase in the lysis of rhu4D5‐coated targets
  • We have shown that costimulation with IL‐2 plus rhu4D5 results in significant production of IFN‐γ by NK cells with concomitant up‐regulation of cell‐surface activation and adhesion molecules
  • It has been previously demonstrated that continuous low‐dose IL‐2 can expand a CD56+ lymphocyte population, and we have now shown that this cell population is a potent mediator of ADCC against rhu4D5 mAb‐coated Her2 / neu+ targets
  • These results suggest that administration of low‐dose IL‐2 can be used to expand NK cell numbers, while higher doses may be used to enhance their cytolytic capacity in the setting of mAb therapy
  • we have demonstrated that NK cell lysis of Her2 / neu+ breast cancer cell lines in the presence of rhu4D5 mAb is markedly enhanced following stimulation with IL‐2
  • we have presented evidence that administration of low‐dose IL‐2 in vivo results in the expansion of a potent NK cell effector population
  • Our experiments suggest that NK cells costimulated with IL‐2 and immobilized IgG can secrete potent immunomodulatory cytokines which may serve to potentiate the anti‐tumor immune response.
  • Nathan Goodyear on 18 Jun 18
     
    low dose IL-2 found to expand NK levels in conjuction in with herceptin in HER-2 positive breast cancer cell lines.
Nathan Goodyear

Hormetic dose response to L-ascorbic acid as an anti-cancer drug in colorectal cancer c... - 0 views

www.nature.com/...s41598-018-29386-7

hermetic dose response prooxidative low dose vitamin C vitamin sodium dependent vitamin C transporter High dose IV vitamin C SVCT C high dose vitamin C

shared by Nathan Goodyear on 11 Aug 22 - No Cached
  • Nathan Goodyear on 11 Aug 22
     
    Low dose vitamin C, via SVCT, increases tumor proliferation; whereas high dose decreases tumor proliferation.
pharmacybiz

High Dexamethasone Dose Test For Severely Ill Covid Patients - 0 views

www.pharmacy.biz/severely-ill-covid-19-patients

Dexamethasone-and-COVID-19 pharmacy-business dose-of-dexamethasone-in-covid-19 is-dexamethasone-effective-for-treating-covid-19 Dexamethasone-dosage

shared by pharmacybiz on 03 Jan 22 - No Cached
  • pharmacybiz on 03 Jan 22
     
    British scientists said on Thursday (December 30) they would be studying whether higher doses of a cheap and widely used steroid called dexamethasone could work better for patients with severe Covid-19 compared to the standard low doses. Last year, the same scientists conducting the large trial, dubbed RECOVERY, showed that dexamethasone was able to save the lives of Covid-19 patients in what was called a "major breakthrough" in the coronavirus pandemic. They had found that a 6 mg daily dose of dexamethasone, which is used to reduce inflammation in diseases such as arthritis, cut death rates by around a third among the most severely ill Covid-19 patients in hospitals. "Given how quickly the Omicron variant is spreading, we can expect to see patients admitted to hospital with severe Covid-19 for a while to come," said Peter Horby, an Oxford University professor co-leading the trial.
Nathan Goodyear

The river blindness drug Ivermectin and related macrocyclic lactones inhibit WNT-TCF pa... - 0 views

www.ncbi.nlm.nih.gov/...PMC4287931

ivermectin cancer WTF Selamectin

shared by Nathan Goodyear on 19 Mar 18 - No Cached
  • WNT signaling
  • early colon cancers commonly display loss of function of the tumor suppressor Adenomatous polyposis coli (APC), a key component of the β-CATENIN destruction complex
  • Other cancers also show an active canonical WNT pathway; these include carcinomas of the lung, stomach, cervix, endometrium, and lung as well as melanomas and gliomas
  • ...31 more annotations...
  • In normal embryogenesis and homeostasis, the canonical WNT pathway is activated by secreted WNT ligands produced in highly controlled context-dependent manners and in precise amounts. WNT activity is transduced in the cytoplasm, inactivates the APC destruction complex, and results in the translocation of activate β-CATENIN to the nucleus, where it cooperates with DNA-binding TCF/LEF factors to regulate WNT-TCF targets and the ensuing genomic response
  • beyond the loss of activity of the APC destruction complex, for instance throughAPC mutation, phosphorylation of β-CATENIN at C-terminal sites is required for the full activation of WNT-TCF signaling and the ensuing WNT-TCF responses in cancer.
  • The WNT-TCF response blockade that we describe for low doses of Ivermectin suggests an action independent to the deregulation of chloride channels
  • involve the repression of the levels of C-terminally phosphorylated β-CATENIN forms and of CYCLIN D1, a critical target that is an oncogene and positive cell cycle regulator.
  • the Avermectin single-molecule derivative Selamectin, a drug widely used in veterinarian medicine (Nolan & Lok, 2012), is ten times more potent acting in the nanomolar range
  • Ivermectin also diminished the protein levels of CYCLIN D1, a direct TCF target and oncogene, in both HT29 and H358 tumor cells
  • Activated Caspase3 was used as a marker of apoptosis by immunohistochemistry 48 h after drug treatment. Selamectin and Ivermectin induced up to a sevenfold increase in the number of activated Caspase3+ cells in two primary (CC14 and CC36) and two cell line (DLD1 and Ls174T) colon cancer cell types (Fig​(Fig2C).2C). All changes were significative
  • The strong downregulation of the expression of the intestinal stem cell genesASCL2 andLGR5 (van der Flieret al, 2009; Scheperset al, 2012; Zhuet al, 2012b) by Ivermectin and Selamectin (Fig​(Fig2D)2D) raised the possibility that these drugs could affect WNT-TCF-dependent colon cancer stem cell behavior
  • Pre-established H358 tumors responded to Ivermectin showing a ˜ 50% repression of growth
  • Ivermectin hasin vivo efficacy against human colon cancer xenografts sensitive to TCF inhibition with no discernable side effects
  • Ivermectin (Campbellet al, 1983), an off-patent drug approved for human use, and related macrocyclic lactones, have WNT-TCF pathway response blocking and anti-cancer activities
  • these drugs block WNT-TCF pathway responses, likely acting at the level of β-CATENIN/TCF function, affecting β-CATENIN phosphorylation status.
  • anti-WNT-TCF activities of Ivermectin and Selamectin
  • Ivermectin has a well-known anti-parasitic activity mediated via the deregulation of chloride channels, leading to paralysis and death (Hibbs & Gouaux, 2011; Lynagh & Lynch, 2012). The same mode of action has been suggested to underlie the toxicity of Ivermectin for liquid tumor cells and the potentiation or sensitization effect of Avermectin B1 on classical chemotherapeutics
  • the specificity of the blockade of WNT-TCF responses we document, at low micromolar doses for Ivermectin and low nanomolar doses for Selamectin, indicate that the blockade of WNT-TCF responses and chloride channel deregulation are distinct modes of action
  • What is key then is to find a dose and a context where the use of Ivermectin has beneficial effects in patients, paralleling our results with xenografts in mice.
  • Cell toxicity appears at doses greater (> 10 μM for 12 h or longer or > 5 μM for 48 h or longer for Ivermectin) than those required to block TCF responses and induce apoptosis.
  • Our data point to a repression of WNT-β-CATENIN/TCF transcriptional responses by Ivermectin, Selamectin and related macrocylic lactones.
  • (i) The ability of Avermectin B1 to inhibit the activation of WNT-TCF reporter activity by N-terminal mutant (APC-insensitive) β-CATENIN as detected in our screen
  • (ii) The ability of Avermectin B1, Ivermectin, Doramectin, Moxidectin and Selamectin to parallel the modulation of WNT-TCF targets by dnTCF
  • (iii) The finding that the specific WNT-TCF response blockade by low doses of Ivermectin and Selamectin is reversed by constitutively active TCF
  • (iv) The repression of key C-terminal phospho-isoforms of β-CATENIN resulting in the repression of the TCF target and positive cell cycle regulator CYCLIN D1 by Ivermectin and Selamectin
  • (v) The specific inhibition ofin-vivo-TCF-dependent, but notin-vivo-TCF-independent cancer cells by Ivermectin in xenografts.
  • These results together with the reduction of the expression of the colon cancer stem cell markersASCL2 andLGR5 (e.g., Hirschet al, 2013; Ziskinet al, 2013) raise the possibility of an inhibitory effect of Ivermectin, Selamectin and related macrocyclic lactones on TCF-dependent cancer stem cells.
  • the capacity of cancer cells to form 3D spheroids in culture, as well as the growth of these, is also WNT-TCF-dependent (Kanwaret al, 2010) and they were also affected by Ivermectin treatment
  • If Ivermectin is specific, it should only block TCF-dependent tumor growth. Indeed, the sensitivity and insensitivity of DLD1 and CC14 xenografts to Ivermectin treatment, respectively, together with the desensitization to Ivermectin actionin vivo by constitutively active TCF provide evidence of the specificity of this drug to block an activated WNT-TCF pathway in human cancer.
  • Ivermectin has a good safety profile since onlyin-vivo-dnTCF-sensitive cancer xenografts are responsive to Ivermectin treatment, and we have not detected side effects in Ivermectin-treated mice at the doses used
  • previous work has shown that side effects from systemic treatments with clinically relevant doses in humans are rare (Yang, 2012), that birth defects were not observed after exposure of pregnant mothers (Pacquéet al, 1990) and that this drug does not cross the blood–brain barrier (Kokozet al, 1999). Similarly, only dogs with mutantABCB1 (MDR1) alleles leading to a broken blood–brain barrier show Ivermectin neurotoxicity (Mealeyet al, 2001; Orzechowskiet al, 2012)
  • Indications may include treatment for incurable β-CATENIN/TCF-dependent advanced and metastatic human tumors of the lung, colon, endometrium, and other organs.
  • Ivermectin, Selamectin, or related macrocyclic lactones could also serve as topical agents for WNT-TCF-dependent skin lesions and tumors such as basal cell carcinomas
  • they might also be useful as routine prophylactic agents, for instance against nascent TCF-dependent intestinal tumors in patients with familial polyposis and against nascent sporadic colon tumors in the general aging population
  • Nathan Goodyear on 19 Mar 18
     
    Ivermectin, a common anti-parasitic, found to inhibit WTF-TCF pathway and decrease c-terminal phosophorylaiton of Beta-CATENIN all resulting in increased aptosis and inhibition of cancer growth in colon cancer cell lines and lung cancer cell lines.
Nathan Goodyear

Dose-ranging study of indole-3-carbinol... [J Cell Biochem Suppl. 1997] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...9589355

I3C indole-3-carbinol breast cancer dose dosing

shared by Nathan Goodyear on 04 Jan 13 - No Cached
  • Nathan Goodyear on 04 Jan 13
     
    Dosing information on I3C.  They found 300-400 mg to be tolerated well and an effective dose for breast cancer chemoprevention.
Nathan Goodyear

A phase II study of chemoneuroimmunotherapy with platinum, subcutaneous low-dose interl... - 0 views

www.ncbi.nlm.nih.gov/...12073777

Melanoma chemotherapy IL-2 melatonin Cancer

shared by Nathan Goodyear on 16 Nov 18 - No Cached
  • Nathan Goodyear on 16 Nov 18
     
    Low dose cisplatin, low dose IL-2 and high dose melatonin as effective as first line therapy in the treatment of melanoma
Nathan Goodyear

Immunological Mechanisms of Low and Ultra-Low Dose Cancer Chemotherapy - 0 views

www.ncbi.nlm.nih.gov/...PMC4542825

immunogenic chemoimmunomodulation low-dose cancer ultra metronomic chemotherapy low-dose chemotherapy chemotherapy

shared by Nathan Goodyear on 03 Jul 20 - No Cached
  • Nathan Goodyear on 03 Jul 20
     
    Low dose and ultra-low dose chemo stimulate the immune system to attack cancer
Nathan Goodyear

A Comparative Analysis of Low-Dose Metronomic Cyclophosphamide Reveals Absent or Low-Gr... - 0 views

cancerres.aacrjournals.org/...3994

maximum tolerated chemotherapy cancer low-dose chemotherapy

shared by Nathan Goodyear on 31 Aug 20 - No Cached
  • Nathan Goodyear on 31 Aug 20
     
    Low-dose chemotherapy significantly reduced toxicity compared to maximum tolerated dosing.
Nathan Goodyear

Vitamin C suppresses cell death in MCF‐7 human breast cancer cells induced by... - 1 views

onlinelibrary.wiley.com/...jcmm.12188

tamoxifen low dose vitamin C breast cancer vitamin C

shared by Nathan Goodyear on 14 Aug 22 - No Cached
frankbkelly liked it
  • Nathan Goodyear on 14 Aug 22
     
    Low dose c/w oral dosing is antioxidative and here counters Tamoxifen breast cancer effects. Miss the point of vitamin C when dose correctly!
Nathan Goodyear

Study Finds High-dose Intravenous Vitamin C Reduces Pain and Inflammation in Those... -... - 0 views

www.prnewswire.com/...inic-scientists-182195661.html

pain inflammation RA rheumatoid arthritis arthritis IV IV vitamin C vitamin C Intravenous vitamin C

shared by Nathan Goodyear on 02 Jun 13 - No Cached
  • Nathan Goodyear on 02 Jun 13
     
    High dose IV vitamin C shown to reduce both pain and inflammation in patients with RA.  This study looked at doses only up to 50 grams.  The specific inflammatory marker that this study looked at was CRP and it was reduced on average by 44%.
Nathan Goodyear

Blood Pressure Effects of Vitamin C | Hypertension - 0 views

hyper.ahajournals.org/...789

blood pressure hypertension vitamin C

shared by Nathan Goodyear on 16 Jan 17 - No Cached
  • Nathan Goodyear on 16 Jan 17
     
    review article of studies on vitamin C and blood pressure finds mixed results.  I think it all comes down to dosing.  The authors highlight 2 studies to make their point. One find a significant reduction and another found a slight increase.  The dosing of the vitamin C was only 500 mg/day.  A woefully inadequate therapeutic dosing of vitamin C, especially when dealing with the significant deficiencies that can be found in disease states.
Nathan Goodyear

http://www.drperlmutter.com/wp-content/uploads/2015/12/Pandit_et_al-Acta_Neurologica_Sc... - 0 views

www.drperlmutter.com/...a_Neurologica_Scandinavica.pdf

statin statin therapy statins brain side effects brain health brain hemorrhage hemorrhage

shared by Nathan Goodyear on 19 Jan 17 - No Cached
  • Nathan Goodyear on 19 Jan 17
     
    study finds significant increase in risk of intracerebral (brain) hemorrhage with high dose statin therapy.  The "high dose" seems to be a fairly regular dose by the patients that walk through my office doors.  This is a meta-analysis
Nathan Goodyear

Hypothalamo-Pituitary-Adrenal Axis Dysfunction in Chronic Fatigue Syndrome, and the Eff... - 0 views

jcem.endojournals.org/...3545.long

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

shared by Nathan Goodyear on 01 May 12 - No Cached
  • We conclude that the improvement in fatigue seen in some patients with chronic fatigue syndrome during hydrocortisone treatment is accompanied by a reversal of the blunted cortisol responses to human CRH
  • These data further suggest that the hypocortisolism found in chronic fatigue syndrome may be secondary to reduced adrenal gland output.
  • 5-mg replacement dose of hydrocortisone, and the remainder 10 mg
  • Nathan Goodyear on 01 May 12
     
    low dose hydrocortisone therapy (defined as 5-10 mg), in this study, was used to treat CFS.  This study found an improvement in symptoms in these patients.  Additionally, low cortisol was found in these patients with CFS.  Their conclusion, was that low adrenal function is a component of CFS and low dose hydrocortisone therapy is an effective treatment.   Now, is the low cortisol as the result of increased metabolism as well?
Nathan Goodyear

JISSN | Full text | Creatine supplementation enhances muscle force recovery after eccen... - 0 views

www.jissn.com/13

creatine recovery muscle sports performance

shared by Nathan Goodyear on 27 Jan 14 - No Cached
  • Nathan Goodyear on 27 Jan 14
     
    Creatine supplementation shown to improve muscle recovery in injury.  The dosing included the standard loading dose at 0.3 g/kg of body weight divided in multiple doses.  Maintenance was at 0.1 g/kg of body weight.
Nathan Goodyear

Testosterone 2% Gel Can Normalize Testosterone Con... [J Sex Med. 2013] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...24283410

testosterone gel therapy treatment men map hormone hormones low T

shared by Nathan Goodyear on 29 Nov 13 - No Cached
  • Nathan Goodyear on 29 Nov 13
     
    Study finds that transdermal testosterone effective in normal and overweight men.  The dosing involved is supra physiologic, especially those with an elevated BMI.  This was likely due to the high dosing to overcome the underlying problem i.e. high aromatase activity.  These studies all need to assess estrogens and inflammatory cytokines to better follow these results
1 - 20 of 676 Next › Last »
Showing 20▼ items per page