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Nathan Goodyear

Informa Healthcare - Journal of Immunotoxicology - 8(1):68 - Summary - 0 views

informahealthcare.com/...1547691X.2010.545086

Mercury toxicity Autism ASD

shared by Nathan Goodyear on 19 May 11 - No Cached
  • Nathan Goodyear on 19 May 11
     
    Autism and Mercury toxicity symptoms identical
Nathan Goodyear

Protective effect of reduced glutathione ... [Chem Biol Interact. 1989] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...2736678

glutathione cisplatin chemotherapy toxicity renal kidney systemic

shared by Nathan Goodyear on 12 Sep 11 - No Cached
  • Nathan Goodyear on 12 Sep 11
     
    glutathione protects against cisplatin induced toxicities
Nathan Goodyear

Molecular basis of cadmium toxicity. [Prog Food Nutr Sci. 1984] - PubMed result - 0 views

www.ncbi.nlm.nih.gov/...6385135

cadmium toxicity molecular basis

shared by Nathan Goodyear on 19 Apr 11 - Cached
  • Cadmium inhibits protein synthesis, carbohydrate metabolism and drug metabolizing enzymes in liver of animals.
  • Cadmium affects both humoral and cell mediated immune response in animals
  • cadmium nephropathy
  • ...3 more annotations...
  • produces hypertension
  • It causes an alterations of cellular functions in lungs
  • Cadmium is also toxic to central nervous system
  • Nathan Goodyear on 19 Apr 11
     
    for you biochemistry junkies, the molecular pathophysiology of cadmium oxicity
Nathan Goodyear

Toxic metals and antioxidants: Part II. The role of antioxidants in arsenic and cadmium... - 0 views

cat.inist.fr/?aModele=afficheN&cpsidt=14869409

antioxidants toxic metals arsenic cadmium

shared by Nathan Goodyear on 19 Apr 11 - No Cached
  • Nathan Goodyear on 19 Apr 11
     
    antioxidants aid in cadmium and arsenic chelation
Nathan Goodyear

Recommendations for Medical Management of Adult Lead Exposure - 0 views

www.ncbi.nlm.nih.gov/...PMC1849937

lead toxicity chelation

shared by Nathan Goodyear on 05 Jul 11 - No Cached
  • Nathan Goodyear on 05 Jul 11
     
    recommendations for acute lead toxicity treatment: chelation
Nathan Goodyear

An extensive new literature concerning low-dose ef... [Environ Health Perspect. 2005] -... - 0 views

www.ncbi.nlm.nih.gov/...16079060

BPA toxic Bisphenol A

shared by Nathan Goodyear on 01 Jul 11 - No Cached
  • reports that the median BPA level in human blood and tissues, including in human fetal blood, is higher than the level that causes adverse effects in mice
  • Nathan Goodyear on 01 Jul 11
     
    low dose exposures of BPA toxic
Nathan Goodyear

Parent bisphenol A accumulation in the human mater... [Environ Health Perspect. 2002] -... - 0 views

www.ncbi.nlm.nih.gov/...12417499

BPA endocrine disurptor

shared by Nathan Goodyear on 01 Jul 11 - No Cached
  • Exposure levels of parent BPA were found within a range typical of those used in recent animal studies and were shown to be toxic to reproductive organs of male and female offspring
  • BPA blood concentrations were higher in male than in female fetuses
  • Nathan Goodyear on 01 Jul 11
     
    Mother's exposure to toxic BPA passed to her child
Nathan Goodyear

Reversible Myocarditis Due to Chronic Lead Poisoning in Childhood - 0 views

www.ncbi.nlm.nih.gov/...PMC2019279

lead toxicity EDTA chelation

shared by Nathan Goodyear on 07 Jul 11 - No Cached
  • Nathan Goodyear on 07 Jul 11
     
    chronic lead toxicity treated with EDTA chelation in children
Nathan Goodyear

http://www.jgld.ro/2009/2/15.pdf - 0 views

www.jgld.ro/15.pdf

Lead lead toxicity liver enzymes

shared by Nathan Goodyear on 09 Mar 15 - No Cached
  • Nathan Goodyear on 09 Mar 15
     
    Lead toxicity associated with liver damage and elevated liver enzymes in case study.
Nathan Goodyear

Evolving landscape of human epidermal growth factor receptor 2-positive breast cancer t... - 0 views

www.sciencedirect.com/...S0960977617300103

HER-2 breast cancer cancer herceptin Perjeta

shared by Nathan Goodyear on 06 Aug 18 - No Cached
  • 15%–20%
  • key mediator of cell growth, differentiation, and survival
  • of higher histological grade and are more likely to invade axillary lymph nodes
  • ...15 more annotations...
  • shortened survival and an increased risk of disease recurrence and metastasis
  • Currently, four HER2-directed agents are approved for the treatment of patients with HER2+ breast cancer: trastuzumab, pertuzumab, lapatinib, and ado-trastuzumab emtansine (T-DM1)
  • biosimilars
  • trastuzumab may provide greater benefit when administered concurrently with chemotherapy rather than after, and this has become the standard approach
  • concurrent use of anthracyclines (ie, doxorubicin or epirubicin) and trastuzumab is not recommended because of an increased risk for cardiac toxicity
    • Nathan Goodyear
      Nathan Goodyear on 06 Aug 18
       
      avoid herceptin in conjuction with antracyclines i.e. doxorubicin
  • Sequential doxorubicin plus cyclophosphamide followed by concomitant paclitaxel or docetaxel and trastuzumab is recommended for most patients
    • Nathan Goodyear
      Nathan Goodyear on 06 Aug 18
       
      top recommended regimen combination
  • Guidelines also recommend trastuzumab in combination with paclitaxel, docetaxel and carboplatin, or docetaxel and cyclophosphamide, particularly for patients with increased risk for cardiac toxicity or those with small (≤1 cm), node-negative HER2+ tumors
    • Nathan Goodyear
      Nathan Goodyear on 06 Aug 18
       
      good alternative in patients with increased risk of cardiac toxicity.
  • guidelines recommend up to 1 year of adjuvant trastuzumab
  • Neoadjuvant chemotherapy with trastuzumab is associated with higher rates of pathologic complete response (pCR) than chemotherapy alone or in combination with lapatinib
  • the combination of trastuzumab, lapatinib, and chemotherapy is not recommended because it failed to demonstrate noninferiority versus trastuzumab and chemotherapy in the adjuvant setting
  • recommend the combination of trastuzumab, pertuzumab, and chemotherapy as neoadjuvant treatment for patients with locally advanced HER2+ breast cancer and for some patients (node-positive or tumor ≥2 cm) with early-stage disease
  • neoadjuvant chemotherapy in combination with pertuzumab and trastuzumab reduced the risk of progression or death by 31% and recurrence or death by 40% versus trastuzumab alone
  • Concurrent chemotherapy and HER2-directed therapy improves survival outcomes over chemotherapy alon
  • dual inhibition of HER2 with trastuzumab and pertuzumab in combination with paclitaxel reduced the risk of death or progression by approximately 40% compared with concurrent trastuzumab and paclitaxel
  • the combination of trastuzumab, pertuzumab, and taxane chemotherapy is the preferred first-line regimen
  • Nathan Goodyear on 06 Aug 18
     
    HER-2 + breast cancer = appx 15-20% of all breast cancers and is a marker of worse prognosis and an indication for targeted immunotherapy blockade.
Nathan Goodyear

High-dose parenteral ascorbate enhanced chemosensitivity of ovarian cancer and reduced ... - 1 views

www.ncbi.nlm.nih.gov/...24500406

cancer ovarian cancer ascorbic acid IV vitamin C IV vitamin C dosing vitamin C chemotherapy

shared by Nathan Goodyear on 22 Jan 18 - No Cached
  • Nathan Goodyear on 22 Jan 18
     
    Proof of conept finds IV vitamin C is synergistic with chemotherapy in ovarian cancer.  In addition, a reduction in toxic side effects were also seen.  Why is vitamin C not used???  The results were found in in vivo and in vitro study.
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

Lipid Peroxidation: Production, Metabolism, and Signaling Mechanisms of Malondialdehyde... - 0 views

www.hindawi.com/...360438

MDA malondialdehyde peroxidation oxidative stress free radicals

shared by Nathan Goodyear on 05 Dec 17 - No Cached
  • Hydroxyl radicals cause oxidative damage to cells because they unspecifically attack biomolecules [22] located less than a few nanometres from its site of generation and are involved in cellular disorders such as neurodegeneration [23, 24], cardiovascular disease [25], and cancer [26, 27].
  • It is generally assumed that in biological systems is formed through redox cycling by Fenton reaction, where free iron (Fe2+) reacts with hydrogen peroxide (H2O2) and the Haber-Weiss reaction that results in the production of Fe2+ when superoxide reacts with ferric iron (Fe3+)
  • other transition-metal including Cu, Ni, Co, and V can be responsible for formation in living cells
  • ...20 more annotations...
  • The hydroperoxyl radical () plays an important role in the chemistry of lipid peroxidation
  • The is a much stronger oxidant than superoxide anion-radical
  • Lipid peroxidation can be described generally as a process under which oxidants such as free radicals or nonradical species attack lipids containing carbon-carbon double bond(s), especially polyunsaturated fatty acids (PUFAs) that involve hydrogen abstraction from a carbon, with oxygen insertion resulting in lipid peroxyl radicals and hydroperoxides as described previously
  • under medium or high lipid peroxidation rates (toxic conditions) the extent of oxidative damage overwhelms repair capacity, and the cells induce apoptosis or necrosis programmed cell death
  • The overall process of lipid peroxidation consists of three steps: initiation, propagation, and termination
  • Once lipid peroxidation is initiated, a propagation of chain reactions will take place until termination products are produced.
  • The main primary products of lipid peroxidation are lipid hydroperoxides (LOOH)
  • Among the many different aldehydes which can be formed as secondary products during lipid peroxidation, malondialdehyde (MDA), propanal, hexanal, and 4-hydroxynonenal (4-HNE) have been extensively studied
  • MDA has been widely used for many years as a convenient biomarker for lipid peroxidation of omega-3 and omega-6 fatty acids because of its facile reaction with thiobarbituric acid (TBA)
  • MDA is one of the most popular and reliable markers that determine oxidative stress in clinical situations [53], and due to MDA’s high reactivity and toxicity underlying the fact that this molecule is very relevant to biomedical research community
  • 4-HNE is considered as “second toxic messengers of free radicals,” and also as “one of the most physiologically active lipid peroxides,” “one of major generators of oxidative stress,” “a chemotactic aldehydic end-product of lipid peroxidation,” and a “major lipid peroxidation product”
  • MDA is an end-product generated by decomposition of arachidonic acid and larger PUFAs
  • Identifying in vivo MDA production and its role in biology is important as indicated by the extensive literature on the compound (over 15 800 articles in the PubMed database using the keyword “malondialdehyde lipid peroxidation” in December 2013)
  • MDA reactivity is pH-dependent
  • When pH decreases MDA exists as beta-hydroxyacrolein and its reactivity increases
  • MAA adducts are shown to be highly immunogenic [177–181]. MDA adducts are biologically important because they can participate in secondary deleterious reactions (e.g., crosslinking) by promoting intramolecular or intermolecular protein/DNA crosslinking that may induce profound alteration in the biochemical properties of biomolecules and accumulate during aging and in chronic diseases
  • MDA is an important contributor to DNA damage and mutation
  • This MDA-induced DNA alteration may contribute significantly to cancer and other genetic diseases.
  • Dietary intake of certain antioxidants such as vitamins was associated with reduced levels of markers of DNA oxidation (M1dG and 8-oxodG) measured in peripheral white blood cells of healthy subjects, which could contribute to the protective role of vitamins on cancer risk
  • 4-HNE is an extraordinarily reactive compound
  • Nathan Goodyear on 05 Dec 17
     
    Great review of lipid peroxidation
Nathan Goodyear

Dietary serine-microbiota interaction enhances chemotherapeutic toxicity without alteri... - 0 views

www.nature.com/...s41467-020-16220-w

cancer nutrition diet

shared by Nathan Goodyear on 16 Jun 20 - No Cached
  • Nathan Goodyear on 16 Jun 20
     
    Diet can increase chemotherapy toxicity by up to 100 fold through alterations in gut microbiome
Nathan Goodyear

Environmental Chemicals in Pregnant Women in the United States: NHANES 2003-2004 - 0 views

www.ncbi.nlm.nih.gov/...PMC3114826

environmental chemicals toxins pregnant women pregnant women

shared by Nathan Goodyear on 04 Dec 12 - No Cached
  • Nathan Goodyear on 04 Dec 12
     
    2011 study finds that 43 toxic chemicals of 163 evaluated found in "virtually all" 268 pregnant women in small study.  Many of these chemical have not been commercially available for 30 years.
Nathan Goodyear

Erectile dysfunction and depression in patients with chronic lead poisoning - Gonulalan... - 0 views

onlinelibrary.wiley.com/...abstract

erectile dysfunction ED lead Pb

shared by Nathan Goodyear on 10 Jun 13 - No Cached
  • Nathan Goodyear on 10 Jun 13
     
    chronic lead toxicity linked with increased ED in men.
Nathan Goodyear

Tolerance and safety of vitamin E: a toxicological position report. - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...1628854

vitamin E vitamins alternative medicine

shared by Nathan Goodyear on 13 Jun 16 - No Cached
  • Nathan Goodyear on 13 Jun 16
     
    Only abstract available here.  The quote that "the toxicity of vitamin E is very low" tells the story.  Always have levels evaluated to ensure need.  In this review of human studies, doses up to 3,200 IU daily "led to no consistent adverse effects".  Also consider the effects of vitamin K effects in those on vitamin E therapy.
Nathan Goodyear

Deficient Glutathione in the Pathophysiology of Mycotoxin-Related Illness - 0 views

www.ncbi.nlm.nih.gov/...PMC3942754

myctotoxins glutathione GSH mold

shared by Nathan Goodyear on 12 Jan 15 - No Cached
  • Decreased function of the enzymes of glutathione production results in a microenvironment depleted of glutathione on a chronic basis
  • In humans, deficiency of glutathione can lead to chronic conditions [97], including chronic asthma
  • Nathan Goodyear on 12 Jan 15
     
    Mycotoxins deplete glutathione production and this depletion of glutathione is a portion go the toxicity/ill effects related to mycotoxins.  This article also points to evidence that glutathione can actually be employed in the treatment of mycotoxin related conditions/illnesses.
wheelchairindia9

Tynor Hot and Cold Pack - 0 views

www.wheelchairindia.com/...Tynor-Hot-and-Cold-Pack

Tynor Hot and Cold Pack hot and cold packs hot and cold pack hot and cold pack buy online hot and cold pack india hot and cold pack therapy buy hot and cold pack tynor hot and cold pack prices

shared by wheelchairindia9 on 01 Apr 16 - No Cached
  • wheelchairindia9 on 01 Apr 16
     
    Tynor Hot and Cold Pack is a convenient device to provide hot fomentation or cold compress. Hot fomentation of the injured or inflamed area enhances the threshold of pain and thus reduces the perception of pain. It has a synergistic effect along with pain relieving drugs. Raising temperature of the injured tissue also enhances the blood profusion and the healing process. Hot fomentation has a relaxing effect. Cold compress helps in reduction of inflammation in injuries, protects by slowing the metabolic rate around the tissue, reduce oedema and bleeding. Cold compress helps in immediately lowering fever, in very high fever conditions. It can be used after an acute injury or surgical procedure. No heat or cryo burns. Requires no holding. Reusable. Easy application. Appealing aesthetics. Tynor Hot and Cold Pack Features Multi functionality Reduce swelling and odema at the site of injury. Muscles spasm and pain. Headache and minor injuries. Versatile design Can be used as either cold or hot pack. Reusable in either hot & cold condition. Temperature range - Can be used from 0 Cº to 75Cº. Longer temperature retention time. Fabric cover ensures no cryo burns or hot skin burns. Physical features Non-toxic, and biodegradable. Gel remains soft and flexible upto 0 degree. Durable, and puncture resistant. Soft, "frost free" PVC cover. Flexible conforms to the body contours. Easy to clean and maintain. Excellent workmanship. Good aesthetics. Elastic belt Holds the pack against the body, No need to hold by hand. Enhances convenience. Tynor Hot and Cold Pack Measurements
Nathan Goodyear

Potential Therapeutic Effects of Curcumin, the Anti-inflammatory Agent, Against Neurode... - 0 views

www.ncbi.nlm.nih.gov/...PMC2637808

curcumin inflammation disease turmeric natural cardiovascular disease CVD autoimmune disease myeloperoxidase Diabetes IBD inflammatory bowel disease

shared by Nathan Goodyear on 15 Oct 13 - No Cached
  • The starting dose was 500 mg/day and if no toxicity was noted, the dose was then escalated to another level in the order of 1,000, 2,000, 4,000, 8,000, and 12,000 mg/day. There was no treatment-related toxicity up to 8 g/day but the bulky volume of the drug was unacceptable to the patients beyond 8 g/day.
  • The serum concentration of curcumin usually peaked at 1 to 2 hours after oral intake of curcumin and gradually declined within 12 hours
  • Nathan Goodyear on 15 Oct 13
     
    Great article on the benefits of curcumin in therapy for inflammation and disease.
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