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Nathan Goodyear

The Risk of Fluoroquinolone-induced Tendinopathy and Tendon Rupture - 0 views

www.ncbi.nlm.nih.gov/...PMC2921747

flouroquinolones ciprofloxacin levoquin tendinitis tendinopathy Tendon rupture

shared by Nathan Goodyear on 02 Aug 17 - No Cached
  • Achilles tendinitis or rupture is among the most serious side effects associated with FQ use
  • The large body of data provided by clinical reports, histopathological examination, and experimental studies provides cogent evidence supporting a direct link between FQ use and tendonitis/tendon rupture
  • Risk factors associated with FQ-induced tendon disorders include age greater than 60 years, corticosteroid therapy, renal failure, diabetes mellitus, and a history of musculoskeletal disorders
  • ...17 more annotations...
  • The average age of FQ-induced tendinopathy is 64 years, with a male-to-female ratio of 2:1, and a 27-percent incidence of bilateral involvement
  • Although more than 95 percent of cases of tendinitis/rupture secondary to FQ involve the Achilles tendon, other reported sites of tendon involvement include the quadriceps, peroneus brevis, and rotator cuff
  • FQs demonstrate a 3.8-fold greater risk for development of Achilles tendinitis/rupture
  • a large population-based case control analysis, patients treated with FQs exhibited a substantially increased risk of developing tendon disorders overall (1.7-fold), tendon rupture (1.3-fold), and ATR (4.1-fold)
  • patients taking FQs with concurrent exposure to corticosteroids were found to experience a compounding effect on the risk of tendon rupture, specifically a 46-fold greater predisposition
  • Some authors have recommended that patients with a history of Achilles tendinitis and advanced age should not be prescribed FQ antibiotics
  • Approximately 50 percent of patients will recover within 30 days, with 25 percent of patients having symptoms persistent for longer than two months
  • The mean latency period between the start of FQ treatment and occurrence of tendinopathy has been reported to be a few hours to months, with a median onset of 6 days
  • The exact pathophysiology of FQ-induced tendinopathy remains elusive
  • it is possible that FQs have a direct cytotoxic effect on enzymes found in mammalian musculoskeletal tissue
  • It has been theorized that FQs disproportionately affect human tendons that have a limited capacity for repair, such as in older patients or structural compromise (i.e., pre-existing tendinopathy or trauma)
  • histopathological findings are similar to those observed in overuse conditions in athletes
  • Treatment with a FQ should be discontinued and physical therapy initiated
  • treatment should include rest and decreasing the physical load on the tendon.
  • Approximately 85 percent of patients present in less than one month
  • Because rupture can occur even late in the course of treatment or after discontinuation of FQ use, patients receiving a FQ should be counseled to seek medical attention immediately if symptoms, such as redness, pain, swelling, and stiffness, develop
  • FQs should be used cautiously in patients with risk factors associated with tendinitis, such as advanced age, history of tendon rupture, corticosteroid use, and/or acute or chronic renal dysfunction
  • Nathan Goodyear on 02 Aug 17
     
    Great review of the link between flouroquinolones and Tendinitis and Tendon rupture.  Yes, there is a direct link.
Nathan Goodyear

Vitamin C Mitigates Oxidative Stress and Tumor Necrosis Factor-Alpha in Severe Communit... - 0 views

www.hindawi.com/...426740

LPS lipopolysaccharides ROS TNF-alpha TNF tumor necrosis factor IL-6 inflammation pneumonia vitamin C

shared by Nathan Goodyear on 06 Dec 17 - No Cached
  • Nathan Goodyear on 06 Dec 17
     
    Cell culture study found that vitamin C inhibited LPS mediated increase in ROS, TNF-alpha, IL-6... The cells were taken from adults with pneumonia
Nathan Goodyear

Low Ascorbate Levels Are Associated with Increased Hypoxia-Inducible Factor-1 Activity ... - 0 views

cancerres.aacrjournals.org/...5749.long

HIF-1 HIF-1alpha vitamin C cancer Hypoxia-inducible Factor 1

shared by Nathan Goodyear on 01 Apr 21 - No Cached
  • Nathan Goodyear on 01 Apr 21
     
    "That ascorbate deficiency compromises HIF hydroxylase activity and upregulates HIF-1 has been shown in vitro in both primary and cancer cells."
Nathan Goodyear

Effect of Ascorbate on the Activity of Hypoxia-inducible Factor in Cancer Cells | Cance... - 0 views

cancerres.aacrjournals.org/...1764.long

Hypoxia-inducible Factor 1 Fe HIF-1 iron vitamin C HIF-1alpha cancer

shared by Nathan Goodyear on 01 Apr 21 - No Cached
  • Nathan Goodyear on 01 Apr 21
     
    "Ascorbate at physiological concentrations (25 μm) strikingly suppressed HIF-1α protein levels and HIF transcriptional targets, particularly when the system was oncogenically activated in normoxic cells. Similar results were obtained with iron supplementation" Here, physiologic levels of plasma AA decrease HIF-1alpha activity.
Nathan Goodyear

Modulation of hypoxia-inducible factor-1 alpha in cultured primary cells by intracellul... - 0 views

www.sciencedirect.com/...S0891584906007611

VEGF cancer GLUT Hypoxia-inducible Factor 1 vitamin C HIF-1alpha HIF-1

shared by Nathan Goodyear on 01 Apr 21 - No Cached
  • Nathan Goodyear on 01 Apr 21
     
    "Induction of HIF-1α by hypoxia (1% O2) or by CoCl2 was markedly inhibited by ascorbate and loading with physiological levels resulted in almost complete reversal of HIF-1α stabilisation. Gene expression was similarly affected, with VEGF mRNA and GLUT-1 up-regulation being inhibited by ascorbate"
Nathan Goodyear

Effects of Transferrin Receptor Blockade on Cancer Cell Proliferation and Hypoxia-Induc... - 0 views

cancerres.aacrjournals.org/...2749.long

HIF-1alpha cancer HIF-1 vitamin C Hypoxia-inducible Factor 1 hypoxia

shared by Nathan Goodyear on 01 Apr 21 - No Cached
  • Nathan Goodyear on 01 Apr 21
     
    "These results indicate that the addition of ascorbate increased the activity of the PHD (propyl hydroxylase) enzymes in down-regulating HIF...."
Nathan Goodyear

Increased Tumor Ascorbate is Associated with Extended Disease-Free Survival and Decreas... - 0 views

www.ncbi.nlm.nih.gov/...PMC3912592

hypoxia HIF-1 IV vitamin C VEGF Hypoxia-inducible Factor 1 vitamin C HIF-1alpha cancer

shared by Nathan Goodyear on 02 Apr 21 - No Cached
  • Nathan Goodyear on 02 Apr 21
     
    Enough said: "There was an inverse relationship between tumor ascorbate content and HIF-1 pathway activation and tumor size. Higher tumor ascorbate content was associated with significantly improved disease-free survival in the first 6 years after surgery with additional disease-free days. This was independent of tumor grade and stage. Survival advantage was associated with the amount of ascorbate in the tumor, but not with the amount in adjacent normal tissue. Our results demonstrate that higher tumor ascorbate content is associated with decreased HIF-1 activation."
Nathan Goodyear

Communication between genomic and non-genomic signaling events coordinate steroid hormo... - 0 views

www.ncbi.nlm.nih.gov/...PMC5864526

genomic signaling cancer hormones non-genomic signaling

shared by Nathan Goodyear on 10 Apr 21 - No Cached
  • steroid hormones typically interact with their cognate receptor in the cytoplasm for AR, glucocorticoid receptor (GR) and PR, but may also bind receptor in the nucleus as appears to often be the case for ERα and ERβ
  • This ligand binding results in a conformational change in the cytoplasmic NRs that leads to the dissociation of HSPs, translocation of the ligand-bound receptor to the nucleus
  • In the nucleus, the ligand-bound receptor dimerizes and then binds to DNA at specific HREs to regulate gene transcription
  • ...25 more annotations...
  • some steroid hormone-induced nuclear events can occur in minutes
  • the genomic effects of steroid hormones take longer, with changes in gene expression occurring on the timescale of hours
  • Classical steroid hormone signaling occurs when hormone binds nuclear receptors (NR) in the cytoplasm, setting off a chain of genomic events that results in, among other changes, dimerization and translocation to the nucleus where the ligand-bound receptor forms a complex with coregulators to modulate gene transcription through direct interactions with a hormone response element (HRE)
  • NRs have been found at the plasma membrane of cells, where they can propagate signal transduction often through kinase pathways
  • Membrane-localized ER, PR and AR have been reported to modulate the activity of MAPK/ERK, phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt), nitric oxide (NO), PKC, calcium flux and increase inositol triphosphate (IP3) levels to promote cell processes including autophagy, proliferation, apoptosis, survival, differentiation, and vasodilation
  • ERα36, a 36kDa truncated form of ERα that lacks the transcriptional activation domains of the full-length protein. Membrane-localized ERα36 can activate pathways including protein kinase C (PKC) and/or mitogen activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) to promote the progression of various cancers
  • G protein-coupled receptor 30 (GPR30), also referred to as G protein-coupled estrogen receptor (GPER), is a membrane-localized receptor that has been observed to respond to estrogen to activate rapid signaling
  • hormone-responsive G protein coupled receptor is Zip9, which androgens can activate
  • GPRC6A is another G protein-coupled membrane receptor that is responsive to androgen
  • androgen-mediated non-genomic signaling through this GPCR can modulate male fertility, hormone secretion and prostate cancer progression
  • non-NR proteins located at the cell surface can bind to steroid hormones and respond by eliciting rapid signaling events
  • Estrogens have been shown to induce rapid (i.e. seconds) calcium flux via membrane-localized ER (mER)
  • ER-calcium dynamics lead to activation of kinase pathways such as MAPK/ERK which can result in cellular effects like migration and proliferation
  • 17β-estradiol (E2) has been reported to promote angiogenesis through the activation of GPER
  • Membrane NRs may also mediate rapid signaling through crosstalk with growth factor receptors (GFR)
  • A similar crosstalk occurs between the receptor tyrosine kinase insulin-related growth factor-1 receptor (IGF-IR) and ERα. Not only does IGF-IR activate ERα, but inhibition of IGF-IR downregulates estrogen-mediated ERα activity, suggesting that IGF-IR is essential for maximal ERα signaling
    • Nathan Goodyear
      Nathan Goodyear on 10 Apr 21
       
      This is a bombshell that shatters the current right brain approach to ER. It completely shatters the concept of eat sugar, whatever you want, with cancer treatment in ER+ or hormonally responsive cancer!
  • Further, ER activates IGF-IR pathways including MAPK
  • GPER is involved in the transactivation of the EGFR independent of classical ER
  • tight interconnection between genomic and non-genomic effects of NRs.
  • non-genomic pathways can also lead to genomic effects
  • androgen-bound AR associates with the kinase Src at the plasma membrane, activating Src which then leads to a signaling cascade through MAPK/ERK
  • However, Src can also increase the expression of AR target genes by the ligand-independent transactivation of AR
  • extranuclear steroid hormone actions can potentially reprogram nuclear NR events
  • estrogen modulated the expression of several genes including endothelial nitric oxide synthase (eNOS) via rapid signaling pathways
  • epigenetic changes can then mediate genomic events in uterine tissue and breast cancer cells
Nathan Goodyear

Quercetin Inhibits the Proliferation and Metastasis of Human Non-Small Cell L... - 0 views

www.ncbi.nlm.nih.gov/...PMC7144538

Src Quercetin cancer NF-kappaB

shared by Nathan Goodyear on 20 May 21 - No Cached
  • Nathan Goodyear on 20 May 21
     
    Quercetin inhibits NF-kappaB through src suppression.
Nathan Goodyear

Hypoxia Regulates Insulin Receptor Substrate-2 Expression to Promote Breast Carcinoma C... - 0 views

cancerres.aacrjournals.org/...8894

HIF-1alpha insulin receptor substrate 2 IRS-2 Akt hypoxia breast cancer cancer

shared by Nathan Goodyear on 14 Jan 21 - No Cached
  • Nathan Goodyear on 14 Jan 21
     
    IRS-2 expression, but not IRS-1 expression, is increased by hypoxia (HIF-1alpha), which selects for tumor cells with increased metastatic potential. IRS-2 is active to mediate insulin-like growth factor I-dependent signals in hypoxia, and enhanced activation of Akt in hypoxia is dependent on IRS-2 expression. It is Akt that increases insulin receptor expression. This ties hypoxia to increase in insulin signaling and insulin receptor expression. Boom!
Nathan Goodyear

High-dose Vitamin C (Ascorbic Acid) Therapy in the Treatment of Patients with Advanced ... - 1 views

ar.iiarjournals.org/...809.long

IV vitamin C IV vitamin C therapy antioxidant antioxidants cancer

shared by Nathan Goodyear on 25 Sep 13 - No Cached
  • Nathan Goodyear on 25 Sep 13
     
    IV vitamin C dosing shown to be safe and effective.  The levels achieved by IV therapy supercedes that able to achieve by oral therapy by several factors.  This review of the data in this study is of high dose IV vitamin C--safety is reassured.
Nathan Goodyear

Redox regulation in cancer - 0 views

www.ncbi.nlm.nih.gov/...PMC2835886

estrogen cancer stem cells reaction" CSC hormones cancer Redox

shared by Nathan Goodyear on 08 Nov 18 - No Cached
  • Mitochondrial electron-transport chain and other oxidizing agents are the prime pathways that generate excess ROS in vivo
  • Permanent modification of genetic material resulting from the oxidative damage is one of the vital steps involved in mutagenesis that leads to carcinogenesi
  • The most frequent DNA mutations caused during oxidative stress, initiated by ionizing radiation and other environmental carcinogens are 7,8-dihydro-8-oxoguanine (8-Oxo-G) and Thymine Glycol (TG)
  • ...3 more annotations...
  • catalase and SOD, GPx, GST
  • insulin like growth factor I, or fibroblast growth factor 2 generates ROS
  • Depletion of GSH increases the sensitivity of cells to ROS
  • Nathan Goodyear on 08 Nov 18
     
    The redox reaction in cancer: great read!
Nathan Goodyear

Opioid growth factor - opioid growth factor receptor axis inhibits proliferation of tri... - 0 views

journals.sagepub.com/...1535370213489492

peptide therapy cancer peptides TNBC breast cancer

shared by Nathan Goodyear on 05 Jul 20 - No Cached
  • Nathan Goodyear on 05 Jul 20
     
    Peptide therapy effective in inhibits proliferation in TNBC.
Nathan Goodyear

The Role of Downstream Signaling Pathways of the Epidermal Growth Factor Receptor for A... - 0 views

www.eurekaselect.com/...article

epidermal growth factor receptor EGFR PI3K_Akt prostate cancer artesunate cancer PI3K PI3k_Akt_mTOR Ras_RAF_MEK_ERK PTEN

shared by Nathan Goodyear on 16 Sep 21 - No Cached
  • Nathan Goodyear on 16 Sep 21
     
    Downstream signaling of EGFR points to artesunate resistance.
spineneuro

Why Robotic Spine Surgery in India Attracting African Patients? - 0 views

www.linkedin.com/...racting-african-hospital-india

affordable cost of robotic spine surgery in India robotic spine surgery in India Dr. Mihir Bapat India Top Minimally Invasive Spine SurgeonMumbai India Best Robotic Spine Surgeons India

shared by spineneuro on 04 Oct 21 - No Cached
  • spineneuro on 04 Oct 21
     
    Nowadays India is becoming the hub for spinal surgery due to the affordable cost of robotic spine surgery in India, cost is the main factor for which foreign patients avail of robotic spine surgical procedures in India For more Enquiry Mail us at enquiry@spineandneurosurgeryhospitalindia.com You can call us at +91-9325887033
Nathan Goodyear

Increased Tumor Ascorbate is Associated with Extended Disease-Free Survival and Decreas... - 0 views

pubmed.ncbi.nlm.nih.gov/24551593

HIF-1alpha Hypoxia-inducible Factor 1 vitamin C colorectal cancer

shared by Nathan Goodyear on 25 Nov 21 - No Cached
  • Nathan Goodyear on 25 Nov 21
     
    Vitamin C increases disease free survival via downregulation of HIF-1alpha activity in colorectal cancer.
spineneuro

Dr Vipul Gupta Artemis Makes Interventional Neuroradiology Simpler And Pain Free - 101 ... - 0 views

www.101pressrelease.com/adiology-simpler-and-pain-free

Dr. Vipul Gupta Artemis Dr. Vipul Gupta interventional neuroradiology Best Interventional Neurologist in Delhi India

shared by spineneuro on 16 Dec 21 - No Cached
  • spineneuro on 16 Dec 21
     
    Dr. Vipul Gupta Artemis said, "Our researchers take part in tasks that discover a couple of factors of interventional neuroradiology, with selected attention at the layout of intracranial stents. Dr. Vipul Gupta Director- Neurointerventional Surgery Email: dr.vipulgupta@neurospinehospital.com Phone No.: +91-9325887033
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