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Nathan Goodyear

Pharmacokinetics of Vitamin C: insights into the oral and intravenous administration of... - 0 views

IV vitamin C cancer vitamin C pharmacokinetics

shared by Nathan Goodyear on 21 Aug 19 - No Cached
  • Nathan Goodyear on 21 Aug 19
     
    to be read.
Nathan Goodyear

Pharmacokinetics and pharmacodynamics of intravenous artesunate during severe malaria t... - 0 views

www.ncbi.nlm.nih.gov/...PMC3489518

malaira artesunate pharmacokinetics dihydroartimisinin

shared by Nathan Goodyear on 02 May 20 - No Cached
  • Nathan Goodyear on 02 May 20
     
    to be read
Nathan Goodyear

Late Disseminated Lyme Disease: Associated Pathology and Spirochete Persistence Post-Tr... - 0 views

ajp.amjpathol.org/...fulltext

Lyme Lyme disease borrelia burgdorferi

shared by Nathan Goodyear on 14 Dec 17 - No Cached
  • In this study, we have demonstrated microscopic pathology ranging from minimal to moderate in multiple different tissues previously reported to be involved with LD, including the nervous system (central and peripheral), heart, skeletal muscle, joint-associated tissues, and urinary bladder 12 to 13 months following tick-inoculation of rhesus macaques by Bb strain B31
  • Based on histomorphology, inflammation consisted predominantly of lymphocytes and plasma cells, with rare scattered histiocytes
  • in rare instances, morphologically intact spirochetes were observed in inflamed brain and heart tissue sections from doxycycline-treated animals
  • ...41 more annotations...
  • colocalization of the Bb 23S rRNA probe was not observed in any of the sections of experimental inoculated animals shown to harbor rare persistent spirochetes (Supplemental Figure S1). Previous in vitro work has shown large decreases in Bb rRNA levels when in a stationary phase of growth despite the majority of spirochetes remaining viable
  • The possibility that the spirochetes were intact but dead also exists, though this may be unlikely given the precedence for viable but non-cultivable B. burgdorferi post-treatment
  • The doxycycline dose utilized in this study (5mg/kg) was based on a previous pharmacokinetic analysis of oral doxycycline in rhesus macaques proven to be comparable to levels achieved in humans and was meant to mimic treatment of disseminated LD
  • In addition to the brain of two treated animals, rare morphologically intact spirochetes immunoreactive to OspA were observed in the heart of one treated animal
  • Although we did not measure the doxycycline levels in the cerebrospinal fluid, they have been found to be 12% to 15% of the amount measured in serum
  • We and others have demonstrated the development of a drug-tolerant persister population when B. burgdorferi are treated with antibiotics in vitro
  • The adoption of a dormant or slow-growing phenotype likely allows the spirochetes to survive and re-grow following removal of antibiotic
  • The basic premise that antibiotic tolerance may be an adaptation of the sophisticated stringent response required for the enzootic cycle by the spirochetes is described in a recent review as well
  • Although current IDSA guidelines recommend intravenous ceftriaxone (2g daily for 30 days) over oral doxycycline for treatment of neuroborreliosis, a randomized clinical trial failed to show any enhanced efficacy of I.V. penicillin G to oral doxycycline for treatment of Lyme neuroborreliosis (no treatment failures were reported in this study of 54 patients).
  • we can speculate that the minimal to moderate inflammation that was observed, especially within the CNS and PNS can, in part, explain the breadth of symptoms experienced by late stage Lyme disease patients, such as cognitive impairment and neuralgia.
  • Erythema migrans, the clinical hallmark of early localized Lyme disease, was observed in one of the rhesus macaques from this study.
  • In 2014, a trailblazing study in mice demonstrated a dramatic decline in B. burgdorferi DNA in the tissues for up to eight months after antibiotic treatment followed by the resurgence of B. burgdorferi growth 12 months after treatment
  • This study provides evidence that the slow-growing spirochetes which persist after treatment, but are not cultivable in standard growth media may remain viable.
  • The first well-documented indication of Lyme disease (LD) in the United States occurred in the early 1970s
  • Lyme, Connecticut.
  • Lyme disease is now known to be caused by multiple closely related genospecies classified within the Bb sensu lato complex, representing the most common tick-borne human disease in the Northern Hemisphere
  • approximately 30,000 physician-reported cases occur annually in the United States, the annual incidence has been estimated to be 10-fold higher by the Centers for Disease Control and Prevention.6
  • Current antibiotic therapy guidelines outlined by the Infectious Disease Society of America (IDSA) are successful in the treatment of LD for the majority of LD patients, especially when administered early in disease immediately following identification of erythema migrans (EM)
  • ‘post-treatment Lyme disease syndrome’ (PTLDS)
  • host-adapted spirochetes that persist in the tissues, probably in small numbers, inaccessible or impervious to antibiotic
  • inflammatory responses to residual antigens from dead organisms
  • residual tissue damage following pathogen clearance;
  • autoimmune responses, possibly elicited by antigenic mimicry
  • Experimental studies on immunocompetent mice, dogs, and rhesus macaques have provided evidence for the persistence of Bb spirochetes subsequent to antibiotic treatment in the form of residual spirochetes detected within tissue by IFA and PCR, and recovered by xenodiagnoses
  • Ten male rhesus macaques
  • half (five) of the NHP received antibiotic treatment, consisting of 5 mg/kg oral doxycycline twice per day.
  • Minimal and focal lymphoplasmacytic inflammation
  • inflammation was observed in the leptomeninges overlying a section of temporal cerebral cortex
  • Minimal localized lymphoplasmacytic choroiditis
  • Peripheral nerves contained minimal to moderate lymphoplasmacytic inflammation with a predilection for collagen-rich epineurium and perivascular spaces
  • Inflammation was observed in 56% (5/9) of the NHPs irrespective of treatment group
  • For all animals, inflammation was reserved to perineural tissue
  • The treatment lasted 28 days
  • Minimal to mild lymphoplasmacytic inflammation of either the myocardial interstitium (Figure 2Figure 2A), pericardium (Figure 2Figure 2B), or combination therein was observed in 60% of NHPs
  • A single morphologically intact spirochete, as indicated by positive red immunofluorescence (Figure 2Figure 2C), was observed in the myocardium of one treated animal
  • mild, multifocal lymphoplasmacytic inflammation was observed in one doxycycline-treated animal
  • three animals exhibited minimal to mild lymphoplasmacytic inflammation affecting joint-associated structures
  • 10% to -20% of human patients treated
  • Multiple randomized placebo-controlled studies which evaluated sustained antimicrobial therapy concluded that there is no benefit in alleviating patients’ symptoms and indicated that long-term antibiotic therapy may even be detrimental to patients due to potential associated complications (ie, catheter infection and/or clostridial colitis)
  • and the rapid clearance of dead spirochetes in a murine model
  • higher doses may be needed to combat neuroborreliosis
  • Nathan Goodyear on 14 Dec 17
     
    persistent borrelia burgdorferia were found in the brain (2) and the heart (1) up to 13 months post standard antibiotic treatment suggesting borrelia burdorferia, the cause of Lyme, can persist in a chronic, persistant state poste acute treatment.
Nathan Goodyear

The acute effect of high-dose intravenous vitamin C and other nutrients on blood pressu... - 0 views

www.ncbi.nlm.nih.gov/...PMC4864764

vitamin C IV vitamin C hypertension vitamin B12 blood pressure cardiovascular disease CVD

shared by Nathan Goodyear on 14 Aug 17 - No Cached
  • the reduction in BP within the first 10–20 min may be primarily attributed to a direct vasodilatory physiological effect, described as venodilation
  • BP reduction observed after 70–90 min is likely attributable to pharmacokinetically plausible vitamin C absorption and vasodilation because of nitric oxide release
  • Pharmacokinetic studies of IVC administration observed peak plasma levels within the first 90 min, with plasma levels reaching 13350 μmol/l for 50 g of IVC
  • ...6 more annotations...
  • Essential hypertension, associated with endothelial dysfunction because of an impaired nitric oxide/l-arginine pathway and impaired vasodilation can be restored by vitamin C
  • marked increase in BP response when IVB12 is administered
  • The mean BP increased significantly up to 12–16 mmHg systolic and diastolic independent of the dosage of vitamin B12
  • The production of norepinephrine, which can stimulate angiotensin-II production, which in turn influences BP, has been suggested as a possible mechanism for the increase in BP with IVB12
  • excess norephinephrine levels stimulate the sympathetic nervous system, leading to increased cortisol production, which has also been linked to increases in BP
  • Animal studies have found higher serum levels of norepinephrine (noradrenaline) in the adrenal medulla of rats receiving methylcobalamin (methyl-vitamin B12)
  • Nathan Goodyear on 14 Aug 17
     
    IV vitamin C in mostly normotensive patients (> 30 grams) reduced blood pressure.  Some of the patients were pre-hypertensive. Vitamin B12 increase the blood pressure.
Nathan Goodyear

Vitamin C Administration by Intravenous Infusion Increases Tumor Ascorbate Content in P... - 0 views

www.ncbi.nlm.nih.gov/...PMC7830882

VEGF IV vitamin C vitamin C colon cancer hypoxia HIF-1alpha cancer HIF-1 GLUT

shared by Nathan Goodyear on 01 Apr 21 - No Cached
  • Nathan Goodyear on 01 Apr 21
     
    Very interesting study. They gave IV vitamin C up to 75 grams to increase tumor delivery and found there was correlation between plasma and tumor levels post resection. This correlation was to a point-saturation curve. Also, there was a reduction in VEGF and hypoxia scores.
Nathan Goodyear

Treatment of pancreatic cancer with intravenous vitamin C: a... : Anti-Cancer Drugs - 0 views

journals.lww.com/...ancer_with_intravenous.10.aspx

metastasis High dose IV vitamin C high dose vitamin C vitamin C IV vitamin C cancer pancreatic cancer

shared by Nathan Goodyear on 09 Mar 21 - No Cached
  • Nathan Goodyear on 09 Mar 21
     
    High dose vitamin C found to be effective in partial regression of pancreatic cancer.
Nathan Goodyear

Intravenous Vitamin C for Cancer Therapy - Identifying the Current Gaps in Our Knowledge - 0 views

www.ncbi.nlm.nih.gov/...PMC6115501

IV vitamin C vitamin C cancer

shared by Nathan Goodyear on 21 May 19 - No Cached
  • Nathan Goodyear on 21 May 19
     
    To read
Nathan Goodyear

High-Dose Intravenous Vitamin C Combined with Cytotoxic Chemotherapy in Patients with A... - 0 views

www.ncbi.nlm.nih.gov/...PMC4388666

IVC "IV vitamin C" "vitamin cancer

shared by Nathan Goodyear on 01 Jun 19 - No Cached
  • Nathan Goodyear on 01 Jun 19
     
    Phase I/II study of IVC with chemotherapy found good safety and tolerability, no oxaloacetate stones and suprisingly, three patients with different types of cancer that experienced unexpected transient stable disease, increased energy and functional improvement...Really?!
Nathan Goodyear

Intravenous vitamin C for reduction of cytokines storm in acute respiratory distress sy... - 1 views

www.ncbi.nlm.nih.gov/...PMC7172861

IV vitamin C cytokine storm acute respiratory distress syndrome ARDS coronavirus COVID19 vitamin C

shared by Nathan Goodyear on 02 Jun 20 - No Cached
  • Nathan Goodyear on 02 Jun 20
     
    IV vitamin C effective against ARDS in COVID19
Nathan Goodyear

Fever Therapy With Intravenously Applied Mistletoe Extracts for Cancer Patients: A Retr... - 0 views

www.ncbi.nlm.nih.gov/...PMC5739132

cancer mistletoe

shared by Nathan Goodyear on 20 Feb 21 - No Cached
  • Nathan Goodyear on 20 Feb 21
     
    Mistletoe for Fever induction therapy.
Nathan Goodyear

High-dose intravenous vitamin C treatment for COVID-19 (a mechanistic approach) Erol Pr... - 0 views

cytokine storm v vitamin C IV vitamin C coronavirus ARDS COVID19

shared by Nathan Goodyear on 04 Jun 20 - No Cached
  • Nathan Goodyear on 04 Jun 20
     
    Nice review of the evidence behind vitamin C's effects in Covid-19 cytokine storm.
Nathan Goodyear

No Reported Renal Stones with Intravenous Vitamin C Administration: A Prospective Case ... - 0 views

www.ncbi.nlm.nih.gov/...PMC5981254

vitamin C kidney stones IV vitamin C

shared by Nathan Goodyear on 13 May 20 - No Cached
  • Nathan Goodyear on 13 May 20
     
    Review finds no real increase in kidney stone risk.
Nathan Goodyear

Penetration of Dihydroartemisinin into Cerebrospinal Fluid after Administration of Intr... - 0 views

www.ncbi.nlm.nih.gov/...PMC148951

dihydroartemisinin artesunate malaria

shared by Nathan Goodyear on 22 May 20 - No Cached
  • Nathan Goodyear on 22 May 20
     
    Artesunate has low lipid solubility and doesn't cross BBB well; but it's high lipid soluble metabolite dihydroartemisinin does.
Nathan Goodyear

Intravenous Vitamin C Administration Improved Blood Cell Counts and Health-Related Qual... - 0 views

www.ncbi.nlm.nih.gov/...PMC6070822

acute myeloid leukemia IV vitamin C vitamin C AML

shared by Nathan Goodyear on 29 May 20 - No Cached
  • Nathan Goodyear on 29 May 20
     
    Case study of IV vitamin C twice weekly for treatment of relapse AML.
Nathan Goodyear

Effect of short-term intravenous ascorbic acid on reducing ferritin in hemodialysis pat... - 0 views

www.ncbi.nlm.nih.gov/...PMC3459518

ferritin vitamin C IV vitamin C

shared by Nathan Goodyear on 24 May 20 - No Cached
  • Nathan Goodyear on 24 May 20
     
    low dose IV vitamin C in patients with dialysis found to lower ferritin levels.
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