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wheelchairindia9

Wheelchair Lightweight - 0 views

www.wheelchairindia.com/...Ultra-Lightweight-Wheelchair

Lightweight And Folding Transport Wheelchair Transport Wheelchair Wheelchair Lightweight Ultra Lightweight Wheelchair Lightweight Wheelchair Karma KM 2500 transport chair

shared by wheelchairindia9 on 06 May 15 - No Cached
  • wheelchairindia9 on 06 May 15
     
    Transport chairs, also known as companion wheelchairs, have four small wheels instead of two small and two large. A transport chair is designed to only be push by caregiver, other common names are 'companion chair' or 'rollabout chair'. A huge variety of different widths and weight capacities are available. A transport wheelchair is a mobility chair designed for convenience, short-distance use and easy handling by a caregiver. Lightweight and foldable, these wheelchairs are easily moved and typically fit in the trunk of most vehicles. There is even a model designed to fold into a bag to be carried over the shoulder. They are much smaller than standard manual wheelchairs and similar in size to the front wheels. Without large rear wheels, the user must rely on someone else to push the chair, which is why the transport chair is often referred to as a companion wheelchair. Karma Travel Wheelchair KM TV 20.2: Karma Travel Wheelchair KM TV 20.2 - 606 T-6 aircraft-grade aluminum-alloy frame provides incredible strength. Easy-to-fold in three seconds. Karma Travel Wheelchair KM TV 20.2 Features: Type: Travel Wheelchair T-6 aircraft-grade aluminum Secure brake improve safety Padded flip back armrest PU front caster & rear wheel Karma Travel Wheelchair KM TV 20.2 Measurements: Weight: 8.9kg Seat width: 39.5cm Tyre: PU front casters and rear wheels Capacity: 100kg Folded size: (L/W/H): 610mm x 350mm x710mm. Ultra Lightweight Wheelchair: Its compact design and feather light weight makes it suitable for people on the go. Ultra Lightweight Wheelchair Specifications: Frame Style : Foldable Frame Material : Aluminium (Light weight) Rear wheel to wheel width in open position (inches) : 20" Handle to Handle : 16" Seat Width (inches): 13" Rear Wheel Size: 7" Front Wheel Size: 5" Seat to floor height (inches): 19" Seat Depth (inches): 13" Back height (inches): 16" Total height (inches): 35" Max User Weight Capacity (kgs): 80 k.g. Net Weigh
Nathan Goodyear

Long-term treatment with the oncolytic ECHO-7 virus Rigvir of a melanoma stage IV M1c p... - 0 views

www.ncbi.nlm.nih.gov/...27457663

Cancer RIGVIR immunotherapy immunotherapy cancer

shared by Nathan Goodyear on 19 Oct 18 - No Cached
  • Nathan Goodyear on 19 Oct 18
     
    3 cases reports of the use of the oncolytic RIGVIR virus in stage III and stage IV disease.
Nathan Goodyear

Rare Occurrence of 3 "H": Hypercalcemia, Hemolytic Anemia and Hodgkin's Lymphoma - 0 views

www.ncbi.nlm.nih.gov/...PMC4925562

Hodgkin's lymphoma Hodgkin's disease hypercalcemia lymphoma

shared by Nathan Goodyear on 21 Aug 18 - No Cached
  • administered zoledronic acid (4 mg). Prednisolone (1 mg/kg/day) was started and simultaneously, she was administered first cycle of ABVD (Adriamycin: 25 mg/m2, Bleomycin: 10 U/m2, Vinblastine: 6 mg/m2 and Dacarbazine: 375 mg/m2), which led to normalisation of serum calcium levels over 4 days and improvement in her hemoglobin levels
  • Etiology of anemia in Hodgkin’s lymphoma is multifactorial. Anemia of chronic disease, decreased red cell survival, infiltration of bone marrow by tumor and marrow suppression by chemotherapy/radiotherapy are the common mechanisms
  • Our case had only a transient response to steroids and chemotherapy. Therefore, she was treated with Rituximab which brought hemolysis under control
  • ...7 more annotations...
  • Mechanism of hypercalcemia in HL has long been suggested to involve extra-renal activation of 1α-hydroxylase leading to production of 1, 25(OD)2 Vitamin D3 or Calcitriol, an active metabolite of Vitamin D, which leads to increased re-absorption of calcium and phosphate from intestine, increased osteoclast activation and bone resorption as well as increased phosphate re-absorption in renal tubules
  • Hypercalcemia of malignancy involves three mechanisms: 1. Humoral hypercalcemia mediated by PTHrP—seen in solid tumors like breast cancer and adult T cell leukemia/lymphoma (ATLL), 2. Direct osteoclast mediated bone resorption due to bony metastasis—seen in solid tumors and multiple myeloma, 3. Calcitriol mediated hypercalcemia—seen in Hodgkin’s and non-Hodgkin’s lymphoma as well as granulomatous disorders like tuberculosis, sarcoidosis, leprosy and disseminated Candidiasis
  • Hypercalcemia in HL is rare and its incidence has been reported as 0.9, 1.6 and 5.4 % in different series
  • The source of 1α-hydroxylase in HL has been postulated as monocytes and macrophages infiltrating the tumor akin to tuberculosis or sarcoidosis and is stimulated by IFN-γ secreted by T-lymphocytes
  • Like sarcoidosis, patients with HL exhibit increased sensitivity to Vitamin D supplements and sunlight, which have been found to precipitate hypercalcemia in these patients
  • Classical biochemical profile in Calcitriol mediated hypercalcemia include: an elevated calcium, normal/slightly elevated phosphate, normal 25(OH) Vitamin D, suppressed PTHrP and PTH, elevated Calcitriol and a normal/increased tubular reabsorption of phosphate
  • not been associated with a poorer prognosis and tends to subside after treatment of the underlying disease
  • Nathan Goodyear on 21 Aug 18
     
    great read on hypercalcemia in hodgkin's lymphoma.
Nathan Goodyear

The Pharmacokinetics and Interactions of Ivermectin in Humans-A Mini-review - 0 views

www.ncbi.nlm.nih.gov/...PMC2751445

Ivermectin

shared by Nathan Goodyear on 19 Mar 18 - No Cached
  • This drug is extensively metabolized by human liver microsomes by cytochrome P450
  • cytochrome P-4503A4, converting the drug to at least 10 metabolites
  • its elimination half-life is around a day
  • ...12 more annotations...
  • second rise in plasma levels (mostly occurring between 6 and 12 h after the dose) suggesting an enterohepatic recycling of the drug
  • Ivermectin is exceptionally potent, with effective dosages levels that are unusually low.
  • the optimal dose of ivermectin is 150 μg/kg, but the frequency of administration is still controversial, ranging from 150 μg/kg once to three times yearly.
  • high lipid solubility of ivermectin, this compound is widely distributed within the body.
  • To interrupt the transmission of onchocerciasis in humans, the combination of ivermectin and doxycycline is highly effective as, in infested patients, the ingestion of the anthelmintic (200 μg/kg, single dose) and the antibacterial (100 mg/kg, daily for 6 weeks)
  • ivermectin interactions with another concurrently administered drugs can occur.
  • This issue becames important, as combination chemotherapy is being used with increasing frequency as resistance to antiparasitic agents is becoming more widespread.
  • haematomatous swellings
  • prothrombin times were significantly above baseline by one week to one month after drug ingestion, suggesting an antagonist effect against vitamin K
  • bleeding disorders were not found in 15,000 patients treated with ivermectin (150 μg/kg)
  • prolonged prothrombin ratios were observed in 148 subjects given ivermectin orally. Although no patients suffered bleeding complications, factor II and VII levels were reduced in most of them, suggesting interference with vitamin K metabolism
  • Ivermectin has a minimal effect on coagulation and concern about mass treatment for this reason appears to be unjustified
  • Nathan Goodyear on 19 Mar 18
     
    Review of Ivermectin as an anti-parasitic.
Nathan Goodyear

The rate of cellular hydrogen peroxide removal shows dependency on GSH: Mathematical in... - 0 views

www.ncbi.nlm.nih.gov/...PMC2268624

GSH glutathione cancer H202

shared by Nathan Goodyear on 30 Jan 18 - No Cached
  • High levels of ROS will lead to a more oxidized redox environment thereby inducing cell damage or even cell death
  • Catalase
  • six members of the peroxiredoxin family of enzymes
  • ...2 more annotations...
  • glutathione peroxidases
  • all reduce H2O2 to water (organic hydroperoxides are reduced to water and the corresponding alcohol) with the electrons coming from GSH, a necessary and specific cofactor.
  • Nathan Goodyear on 30 Jan 18
     
    good review of the interaction between H202 and the glutathione pathway.  This has significant implications in the mechanism of action in cancer cells with IV vitamin C.
Nathan Goodyear

microRNA Expression in Ethnic Specific Early Stage Breast Cancer: an Integration and Co... - 0 views

www.nature.com/...s41598-017-16978-y

genetics cancer epigenetics breast cancer

shared by Nathan Goodyear on 06 Feb 18 - No Cached
mamdouh_hfz liked it
  • dysregulated miRNA could be involved in tumor cell proliferation and growth as well as cell cycle progression
  • under-expression of miR-497, 376c and 1271 in Lebanese breast cancer tissues
  • The upregulated miR-183 in our samples was predicted to be responsible for the decrease in expression of the BTG1 mRNA whose protein is involved in cell cycle arrest and apoptosis in breast cancer cells18.
  • ...9 more annotations...
  • nother molecule related to cell proliferation that was over-expressed in our data and suggested as a target of downregulated miR-376c is AURKA
  • the over-expression of miR-183 and miR-21 in Lebanese breast cancer tissues is consistent with downregulation of two important tumor suppressor predicted targets: AKAP12 whose protein regulates cellular adhesion dynamics by controlling cytoskeletal architecture, cell migration, and mitogenic signaling20; and LATS2 whose protein causes cell cycle arrest
  • dysregulation in cancer particularly in breast cancer highlights their importance in tumor development
  • mRNA-miRNA integration analysis of early breast cancer revealed a potential role of miRNA in increasing cellular proliferation and progression, and decreasing invasion and migration
  • most of the miRNA dysregulated in Lebanese breast cancer patients are similar to those dysregulated in American patients, differences in miRNA expression exist and could be attributed either to the patients’ age at diagnosis or to ethnic variation in miRNA epigenetic regulation and sequence variation of pre-miRNA
  • the number one cancer killer of women worldwide
  • microRNA (miRNA) are small non-coding 18–25 nucleotide RNA molecules currently being studied as potential diagnostic, prognostic and therapeutic biomarkers for cancer and other diseases
  • Extensive research on these post-transcriptional modulators has proven that they are deregulated in breast cancerous tissues and even in biological fluids from breast cancer patients
  • five candidate miRNAs (miR-10b, miR-148b, miR-221, miR-21, and miR-155)
  • Nathan Goodyear on 06 Feb 18
     
    Epigenetics plays a role, via disregulated miRNA, in increased cell growth, progression, and invasion in Lebanese women with breast cancer.  It is not just genetics that play a role, but epigenetics.
Nathan Goodyear

Immune responses to malignancies - 0 views

www.ncbi.nlm.nih.gov/...PMC3721350

cancer immune system

shared by Nathan Goodyear on 18 Apr 18 - No Cached
  • increased densities of T-cell infiltrates with a high proportion of CD8+ T cells within primary colorectal carcinomas were associated with a significant protection against tumor recurrence
  • coexpression of genes mediating cytotoxicity and TH1 adaptive immune responses accurately predicted survival in patients with colorectal carcinoma independently of the metastatic status.
  • tumor-specific cytolytic T lymphocytes (CTLs)
  • ...10 more annotations...
  • tumor-associated antigens (TAs)
  • Proinflammatory cytokines secreted by inflammatory cells can contribute to tumor progression, and soluble factors produced by the tumor in response to nonspecific or tumor-specific signals, such as prostaglandin E2 (PGE2), adenosine, or TGF-β, downregulate functions of immune cells
  • they are largely ineffective in arresting tumor growth, although they can proliferate and mediate antitumor cytotoxicity on their removal from the tumor bed and ex vivo IL-2 activation.42
  • DCs (HLA-DR+CD86+CD80+CD14−) are nature’s best APCs
  • They are a common component of tumor immune infiltrates and are responsible for the uptake, processing, and cross-presentation of TAs to naive or memory T cells, thus playing a crucial role in the generation of tumor-specific effector T cells
  • DCs control the induction of Treg cells. In patients with cancer, cellular interactions between antigen-presenting DCs and T cells lead to expansion and accumulation of Treg cells at the tumor site and in the periphery
  • NK cells (CD3−CD56+CD16+), which mediate innate immunity and contain both perforin-rich and granzyme-rich granules, are well equipped to mediate lysis of tumor cells
  • B cells (CD19+, CD20+) are also rare in most human tumors, with the exception of breast cancer and melanoma
  • The initial acute inflammation involving the recruitment and influx of antitumor effector cells is replaced by chronic inflammation in later stages of tumor progression
  • Tissue hypoxia plays a major role in shaping the nature of immune infiltrates in tumors
  • Nathan Goodyear on 18 Apr 18
     
    Another great review of the immune system during different stages of carcinogenesis; how the cancer manipulates the immue system to cloak itself from the immune system.
Nathan Goodyear

The Contribution of Cytotoxic Chemotherapy to 5-year Survival in Adult Malignancies | C... - 0 views

www.scribd.com/...Survival-in-Adult-Malignancies

chemotherapy cancer

shared by Nathan Goodyear on 15 May 18 - No Cached
  • In this group, the 5-year survivalrateduesolelytocytotoxicchemotherapywas14%
  • There is also no convincing evidence that usingregimens with newer and more expensive drugs are anymore beneficial than the regimens used in the 1970s
  • two systematic reviews of chemotherapy inrecurrent or metastatic breast cancer have not been able toshow any survival benefit
  • ...12 more annotations...
  • The five most common adult malignancies (colorectal, breast, prostate, melanoma and lung cancer)
  • n breast cancer, the optimal regimen(s) for cytotoxicchemotherapy in recurrent/metastatic disease are still notdefined, despite over 30 years of ‘research’ and a plethora of RCTs since the original Cooper regimen was published in1969
  • The five most ‘chemo-sensitive’ cancers,namely testis, Hodgkin’s disease and non-Hodgkin’s lym- phoma, cervix and ovary
  • only 13 out of the 22 malignancies evaluated showed any improvement in 5-year survival, and theimprovement was greater than 10% in only three of those13 malignancies
  • the contribution of curative and adjuvant cytotoxic chemotherapy to 5-year survival in adults is 2.3% in Australia and 2.1% in the USA
  • a benefit of less than 2.5% is likely to be applicable in other developed countries
  •   Overview The Contribution o
  • the benefit of cytotoxic chemotherapy may have been overestimated for cancers of oesophagus, stomach,rectum and brain.
  • this reflects the presentation of results as a ‘reduction in risk’ rather than asan absolute survival benefit[89,90]and by exaggerating theresponse rates by including ‘stable disease’
  • recent studies have documented impaired cognitive function inwomen receiving adjuvant treatment for breast cancer
  • the 5-year survival rate due solely to cytotoxicchemotherapy was 1.6%
  • the value of palliative chemotherapy has beenquestioned
  • Nathan Goodyear on 15 May 18
     
    Incredibly low impact of cytotoxic chemotherapy despite its wide spread utilization.  This article referenced cost yet did not evaluate the cost of cytotoxic side effect.  The question to answer: is Cytotoxic chemotherapy a valid treatment, at all, for the majority of cancers.
Nathan Goodyear

Frontiers | Management of Glioblastoma Multiforme in a Patient Treated With Ketogenic M... - 0 views

www.frontiersin.org/...full

press-pulse therapy hyperbaric ketogenic metabolic therapy cancer ketogenic diet Glioblastoma glioblastoma multiforme HBOT nutrition

shared by Nathan Goodyear on 01 Apr 18 - No Cached
  • The SOC for GBM was modified in this patient to initiate KMT prior to surgical resection, to eliminate steroid medication, and to include HBOT as part of the therapy
  • the greatest therapeutic benefit for patients (near 1.0)
  • The observed reduction in blood glucose in our patient would reduce lactic acid fermentation in the tumor cells, while the elevation of ketone bodies would fuel normal cells thus protecting them from hypoglycemia and oxidative stress
  • ...30 more annotations...
  • Previous studies showed that GBM survival and tumor growth was correlated with blood glucose levels
  • Evidence indicates that glioma cells cannot effectively use ketone bodies for energy due to defects in the number, structure, and function of their mitochondria
  • The accuracy of the GKI as a predictor for therapeutic efficacy, however, is better when ketone bodies are measured from the blood than when measured from the urine
  • A reduction of glucose-driven lactic acid fermentation would not only increase tumor cell apoptosis, but would also reduce inflammation and edema in the tumor microenvironment thus reducing tumor cell angiogenesis and invasion
  • Besides serving as a metabolic fuel for GBM, glutamine is also an essential metabolite for normal immune cells
  • therapies that inhibit glutamine availability and utilization must be strategically employed to avoid inadvertent impairment of immune cell functions
  • we used the non-toxic green tea extract, EGCG, and chloroquine in an attempt to limit glutamine availability to the tumor cells
  • EGCG is thought to target the glutamate dehydrogenase activity that facilitates glutamine metabolism in GBM cells
  • Chloroquine, on the other hand, will inhibit lysosomal digestion thus restricting fermentable amino acids and carbohydrates from phagocytosed materials in the tumor microenvironment
  • HBOT to increase oxidative stress in the tumor cells
  • As glucose and glutamine fermentation protect tumor cells from oxidative stress, reduced availability of these metabolites under ketosis could enhance the therapeutic action of HBOT, as we recently described
  • Prior to subtotal tumor resection and standard of care (SOC), the patient conducted a 72-h water-only fast
  • Following the fast, the patient initiated a vitamin/mineral-supplemented ketogenic diet (KD) for 21 days that delivered 900 kcal/day
  • KD (increased to 1,500 kcal/day at day 22
  • the patient received metformin (1,000 mg/day), methylfolate (1,000 mg/day), chloroquine phosphate (150 mg/day), epigallocatechin gallate (400 mg/day), and hyperbaric oxygen therapy (HBOT) (60 min/session, 5 sessions/week at 2.5 ATA)
  • Biomarkers showed reduced blood glucose and elevated levels of urinary ketones with evidence of reduced metabolic activity (choline/N-acetylaspartate ratio) and normalized levels of insulin, triglycerides, and vitamin D
  • This is the first report of confirmed GBM treated with a modified SOC together with KMT and HBOT, and other targeted metabolic therapies
  • Glioblastoma multiforme (GBM) is the most common and malignant of the primary adult brain cancers
  • less than 20% of younger adults generally survive beyond 24 months
  • glucose and glutamine are the primary fuels that drive the rapid growth of most tumors including GBM
  • Glucose drives tumor growth through aerobic fermentation (Warburg effect), while glutamine drives tumor growth through glutaminolysis
  • The fermentation waste products of these molecules, i.e., lactic acid and succinic acid, respectively, acidify the tumor microenvironment thus contributing further to tumor progression
  • Glucose and glutamine metabolism is also responsible for the high antioxidant capacity of the tumor cells thus making them resistant to chemo- and radiotherapies
  • The reliance on glucose and glutamine for tumor cell malignancy comes largely from the documented defects in the number, structure, and function of mitochondria and mitochondrial-associated membranes
  • These abnormalities cause the neoplastic GBM cells to rely more heavily on substrate level phosphorylation than on oxidative phosphorylation for energy
  • dexamethasone not only increases blood glucose levels but also increases glutamine levels through its induction of glutamine synthetase activity
    • Nathan Goodyear
      Nathan Goodyear on 21 May 18
       
      use mannitol instead
  • Calorie restriction and restricted KD are anti-angiogenic, anti-inflammatory, anti-invasive, and also kill tumor cells through a proapoptotic mechanism
  • Evidence also shows that therapeutic ketosis can act synergistically with several drugs and procedures to enhance cancer management improving both progression free and overall survival
  • hyperbaric oxygen therapy (HBOT) increases oxidative stress on tumor cells especially when used alongside therapies that reduce blood glucose and raise blood ketones
  • The glutamine dehydrogenase inhibitor, epigallocatechin gallate (EGCG) is also proposed to target glutamine metabolism
  • Nathan Goodyear on 01 Apr 18
     
    Case study of Glioblastoma treated with ketogenic metabolic therapy as an adjuct to modified standard therapy.
Nathan Goodyear

Therapeutic hyperthermia: The old, the new, and the upcoming - Critical Reviews in Onco... - 1 views

www.croh-online.com/...fulltext

hyperthermia hyperthermic therapy cancer oncology

shared by Nathan Goodyear on 30 Aug 18 - No Cached
  • not well understood, but it is felt to be a combination of both heat-induced necrosis and of protein inactivation (e.g., repair enzymes) as opposed to DNA damage
  • alterations in tumor cytoskeletal and membrane structures, which disrupt cell motility and intracellular signal transduction
  • A common explanation for HT-enhancement of RT and CT involves inhibition of homologous recombination repair of double-strand DNA breaks, preventing cells from repairing sub-lethal damage
  • ...15 more annotations...
  • it does appear to inhibit rejoining of RT-induced DNA breaks more than is commonly observed after RT alone
  • HT damages cells and enhances RT and CT sensitivity as a function of both temperature and duration of treatment
  • as temperature or duration increase, the rate of cell killing also increases
  • At temperatures above 42 °C, tumor vasculature is damaged, resulting in decreased blood flow
  • Cancer cells are particularly vulnerable to heating; in vivo studies have shown that temperatures in the range of 40–44 °C cause more selective damage to tumor cells
  • cancerous blood vessels are chaotic, leaky, and inefficient
  • selective cytotoxic effect on tumor cells include inhibition of key cancer cell-signaling pathways such as AKT, inducing apoptosis, suppression of cancer stem cell proliferation, and others
  • increase in immunological attacks against tumors after HT, which were believed to be achieved through activation of HSPs and subsequent modulation of the innate and adaptive immune responses against tumor cells
  • HT does lead to activation of the immune system and HSP-induced cell death through modification of the tumor cell surface
  • These HSPs and tumor antigens are taken up by dendritic cells and macrophages and go on to induce specific anti-tumor immunity
  • In vivo studies demonstrate HT-enhancement of NK cell activity, and HT has been shown to increase neutrophilic granulocytes with anti-tumor activity
  • it has become increasingly clear that HT results in immune stimulation, through both direct heat-mediated cell killing as well as innate and adaptive immune system modulation
  • The term hyperthermia is used in this review to refer to heating within the clinically accepted range of 40–45 °C
  • temperatures above 42.5–43 °C the exposure time can be halved with each 1 °C increase while maintaining equivalent cell killing
  • gradual heating at 43 °C for 1 h worked through an apoptotic pathway
  • Nathan Goodyear on 30 Aug 18
     
    Comprehensive review of hyperthemic therapy.
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

Substantial contribution of extrinsic risk factors to cancer development - 0 views

www.ncbi.nlm.nih.gov/...PMC4836858

cancer lifestyle

shared by Nathan Goodyear on 03 Jan 18 - No Cached
  • Here we provide evidence that intrinsic risk factors contribute only modestly (<10~30%) to cancer development
  • we conclude that cancer risk is heavily influenced by extrinsic factors. These results carry immense consequences for strategizing cancer prevention
  • cancers are proposed to originate from the malignant transformation of normal tissue progenitor and stem cells
  • ...14 more annotations...
  • “Intrinsic processes” include those that result in mutations due to random errors in DNA replication whereas “extrinsic factors” are environmental factors that affect mutagenesis rates (such as UV radiation, ionizing radiation, and carcinogens
  • intrinsic factors do not play a major causal role.
  • intrinsic cancer risk should be determined by the cancer incidence for those cancers with the least risk in the entire group controlling for total stem cell divisions
  • if one or more cancers would feature a much higher cancer incidence, for example, lung cancer among smokers vs. non-smokers, then this most likely reflects additional (and probably extrinsic) risk factors (smoking in this case)
  • Particularly, for breast and prostate cancers, it has long been observed that large international geographical variations exist in their incidences (5-fold for breast cancer, 25-fold for prostate cancer)14, and immigrants moving from countries with lower cancer incidence to countries with higher cancer rates soon acquire the higher risk of their new country
  • Colorectal cancer is another high-incidence cancer that is widely considered to be an environmental disease17, with an estimated 75% or more colorectal cancer risk attributable to diet
  • melanoma, its risk ascribed to sun exposure is around 65–86%
  • non-melanoma basal and squamous skin cancers, ~90% is attributable to UV
  • 75% of esophageal cancer, or head and neck cancer are caused by tobacco and alcohol
  • HPV may cause ~90% cases in cervical cancer23, ~90% cases in anal cancer24, and ~70% in oropharyngeal cancer
  • HBV and HCV may account for ~80% cases of hepatocellular carcinoma
  • H pylori may be responsible for 65–80% of gastric cancer
  • While a few cancers have relatively large proportions of intrinsic mutations (>50%), the majority of cancers have large proportions of extrinsic mutations, for example, ~100% for Myeloma, Lung and Thyroid cancers and ~80–90% for Bladder, Colorectal and Uterine cancers, indicating substantial contributions of carcinogen exposures in the development of most cancers
  • onsistent estimate of contribution of extrinsic factors of >70–90% in most common cancer types. This concordance lends significant credibility to the overall conclusion on the role of extrinsic factors in cancer development
  • Nathan Goodyear on 03 Jan 18
     
    Really great read.  Cancer is a majority lifestyle disease.
Nathan Goodyear

A survey on anticancer effects of artemisinin, iron, miconazole, and butyric acid on 56... - 0 views

www.cancerjournal.net/article.asp

artesunate artemisinin cancer Miconazole

shared by Nathan Goodyear on 14 Jun 19 - No Cached
  • Nathan Goodyear on 14 Jun 19
     
    Miconazole found to augment artemisinin + fe in treatment of cancer.
Nathan Goodyear

Melatonin enhances hyperthermia-induced apoptotic cell death in human leukemia cells - ... - 0 views

scholars.uthscsa.edu/...uced-apoptotic-cell-death-in-h

hyperthermia melatonin apoptosis cancer leukemia

shared by Nathan Goodyear on 13 Oct 20 - No Cached
  • Nathan Goodyear on 13 Oct 20
     
    Melatonin and hyperthermia synergistic in stimulation of apoptosis.
indian-health

How Long to Wait For New Aortic Valve Replacement Surgery Procedures? - 0 views

www.briefingwire.com/...replacement-surgery-procedures

Valve Replacement Top Cardiac Surgery Hospitals Mumbai India Valve Replacement Surgery India Cost of Valve Replacement Surgery India Valve Replacement Surgery Cost in India Top Cardiac Surgery Hospitals Mumbai Best Hospitals for Heart surgery Mumbai Top H

shared by indian-health on 29 Nov 21 - No Cached
  • indian-health on 29 Nov 21
     
    More than 50,000 #TAVRprocedures have been executed with the #lowCostof #Valvereplacementsurgery in #India by #Tophearthospitals of #Mumbai. Read Full Press https://bit.ly/3xBbOOQ
Nathan Goodyear

Toxicity of the spike protein of COVID-19 is a redox shift phenomenon: A novel therapeu... - 0 views

www.sciencedirect.com/...S0891584923005014

COVID19 COVID-19 cancer inflammation SARS-CoV-2 spike proteins COVID spikeopathy

shared by Nathan Goodyear on 01 Sep 23 - No Cached
  • Redox shift is due to Warburg effect and mitochondrial impairment.
  • Redox shift is due to Warburg effect and mitochondrial impairment.
  • Redox shift is due to Warburg effect and mitochondrial impairment.
  • ...88 more annotations...
  • The cytokine storm is a consequence of mitochondrial dysfunction
  • The cytokine storm is a consequence of mitochondrial dysfunction
  • The cytokine storm is a consequence of mitochondrial dysfunction
  • The cytokine storm is a consequence of mitochondrial dysfunction
  • Lipoic acid, Methylene Blue and Chlorine dioxide relieve COVID-19 spike protein toxicity
  • Lipoic acid, Methylene Blue and Chlorine dioxide relieve COVID-19 spike protein toxicity
  • Lipoic acid, Methylene Blue and Chlorine dioxide relieve COVID-19 spike protein toxicity
  • Lipoic acid, Methylene Blue and Chlorine dioxide relieve COVID-19 spike protein toxicity
  • most diseases display a form of anabolism due to mitochondrial impairment
  • most diseases display a form of anabolism due to mitochondrial impairment
  • most diseases display a form of anabolism due to mitochondrial impairment
  • infection by Covid-19 follows a similar pattern
  • chronic inflammation
  • Long-term effects include redox shift and cellular anabolism as a result of the Warburg effect and mitochondrial dysfunction
  • Long-term effects include redox shift and cellular anabolism as a result of the Warburg effect and mitochondrial dysfunction
  • Long-term effects include redox shift and cellular anabolism as a result of the Warburg effect and mitochondrial dysfunction
  • Long-term effects include redox shift and cellular anabolism as a result of the Warburg effect and mitochondrial dysfunction
  • infection by Covid-19 follows a similar pattern
  • unrelenting anabolism leads to the cytokine storm,
  • unrelenting anabolism leads to the cytokine storm,
  • unrelenting anabolism leads to the cytokine storm,
  • chronic inflammation
  • chronic inflammation
  • infection by Covid-19 follows a similar pattern
  • Lipoic acid and Methylene Blue have been shown to enhance the mitochondrial activity, relieve the Warburg effect and increase catabolism
  • Lipoic acid and Methylene Blue have been shown to enhance the mitochondrial activity, relieve the Warburg effect and increase catabolism
  • Lipoic acid and Methylene Blue have been shown to enhance the mitochondrial activity, relieve the Warburg effect and increase catabolism
  • Methylene Blue, Chlorine dioxide and Lipoic acid may help reduce long-term Covid-19 effects by stimulating the catabolism
  • Methylene Blue, Chlorine dioxide and Lipoic acid may help reduce long-term Covid-19 effects by stimulating the catabolism
  • Methylene Blue, Chlorine dioxide and Lipoic acid may help reduce long-term Covid-19 effects by stimulating the catabolism
  • direct consequence of redox iMeBalance, itself a consequence of decreased energy yield by the mitochondria
  • direct consequence of redox iMeBalance, itself a consequence of decreased energy yield by the mitochondria
  • mitochondrial dysfunction and increased levels of lactate, which are important characteristics of metabolic shift and Warburg effect in many diseases
  • mitochondrial dysfunction and increased levels of lactate, which are important characteristics of metabolic shift and Warburg effect in many diseases
  • increased lactate dehydrogenase activity (LDH) was observed in COVID-19 patients
  • increased lactate dehydrogenase activity (LDH) was observed in COVID-19 patients
  • almost every disease presents an increased anabolism
  • almost every disease presents an increased anabolism
  • cell division is the most sophisticated way to release entropy
  • cell division is the most sophisticated way to release entropy
    • Nathan Goodyear
      Nathan Goodyear on 01 Sep 23
       
      Wow
    • Nathan Goodyear
      Nathan Goodyear on 01 Sep 23
       
      Wow
  • transition from catabolism to anabolism is driven by a redox shift
  • transition from catabolism to anabolism is driven by a redox shift
  • viral spike protein binds to ACE2 receptor of the host cell [22,23].
  • redox signaling plays an important role in regulating immune function and inflammation, and disruptions in this signaling can lead to excessive cytokine production and immune system activation
  • Aging is associated with a poor control of the redox balance
  • thiol/disulfide homeostasis
  • reduced extracellular environment in the elderly and the increased susceptibility to Covid-19 infection
  • reduced extracellular environment in the elderly and the increased susceptibility to Covid-19 infection
  • Redox signaling tightly modulates the inflammatory response and oxidative stress has been reported in acute Covid-19
  • People at high risk are the elderly, patients suffering from metabolic syndrome such as obesity, or those suffering from chronic diseases such as cancer or inflammation
  • COVID-19 patients with severe disease have higher levels of oxidative stress markers and lower antioxidant levels
  • oxidative stress can activate the NLRP3 inflammasome, which is a protein complex that plays a key role in the cytokine storm
  • inflammation leads to the formation of ROS and RNS, while redox iMeBalance results in cellular damage, which in turn triggers an inflammatory response
  • persistently elevated mtROS triggers endothelial dysfunction and inflammation, which results in a vicious loop involving ROS, inflammation, and mitochondrial dysfunction
  • Damaged mitochondria releasing ROS induce inflammation via the NLRP3 inflammasome
  • Damaged mitochondria releasing ROS induce inflammation via the NLRP3 inflammasome
  • reduced environment during the cytokine storm
  • IL-2 is highly up-regulated in Covid-19 patients [37], and IL-2 is known to significantly stimulate the generation of NO in patients
  • Nitric acid is also the key mediator of IL-2-induced hypotension and vascular leak syndrome
  • mitochondrial dysfunction has been linked to the pathogenesis of Covid-19
  • mitochondrial dysfunction triggered by SARS-CoV-2 leads to damage to the mitochondria
  • mitochondrial dysfunction triggered by SARS-CoV-2 leads to damage to the mitochondria
  • As catabolism is decreased, entropy is released through anabolism
  • Elevated levels of lactate, a characteristic of the Warburg effect, were also reported in the high-risk Covid-19
  • elevated levels of ventricular lactic acid consistent with oxidative stress
  • A decrease of ΔΨm is implicated in several inflammation-related diseases
  • decrease in ΔΨm in leucocytes from Covid-19 patients
  • vaccinated with RNA or DNA vaccines triggering the synthesis of the viral spike protein in human cells
  • viral reactivation in varicella-zoster virus [55] or hepatitis [56], coagulopathy and resulting stroke and myocarditis following both DNA-based vaccines [57] and RNA-based vaccines
  • Covid-19, mitochondrial impairment
  • characteristic of the Warburg effect is present in almost every disease and appears to be a central feature in most of the hallmarks of cancer
  • inflammation, mitochondrial dysfunction and increased lactate concentrations in the extracellular fluid
  • In Covid-19, like any inflammation, there is a metabolic rewiring where cells rely on glycolysis
  • As the mitochondria are impaired, the infected cell cannot catabolize efficiently. It will release lactic acid in the blood stream
    • Nathan Goodyear
      Nathan Goodyear on 01 Sep 23
       
      Mitochondrial impairment
  • Striking similarities are seen between cancer, Alzheimer's disease and Covid-19, all related to the Warburg effect
  • Cancer, inflammation, Alzheimer's, and Parkinson's diseases share a common peculiarity, the inability of the cell to export entropy outside the body in the harmless form of heat
    • Nathan Goodyear
      Nathan Goodyear on 01 Sep 23
       
      Entropy: lack of order or predictability; gradual decline into disorder.
  • MEB relieves the Warburg effect [87], improves memory [77], is active in the treatment of depressive episodes [79,80] and reduces the importance of ischemic strokes
  • MEB relieves the Warburg effect [87], improves memory [77], is active in the treatment of depressive episodes [79,80] and reduces the importance of ischemic strokes
  • MEB has been shown to inhibit SARS-Cov-2 replication in vitro
  • MEB has been shown to inhibit SARS-Cov-2 replication in vitro
  • It has been shown that Covid-19-patients treated with MEB, have a significant reduction in hospital stay duration and mortality
  • MeB is an acceptor-donor molecule
  • MeB + can take a pair of electrons (of H atoms) and MeBH can release this pair easily, so that MeB is partially recycled like a catalyst
  • MeB acts as an electron bridge between a donor (FADH2, FMNH, NADH) and an acceptor (complex IV of ETC or oxygen itself)
  • As a coenzyme of pyruvate dehydrogenase (PDH), alpha-lipoic acid (ALA) initiates the formation of acetyl-CoA to feed the TCA cycle
  • ALA enhances the catabolism of carbon. cycle and therefore may reduce the Warburg effect and consequently, lactate production
  • Methylene Blue plays a similar role after the TCA cycle, by carrying electrons to complex IV of the electron transport chain
  • Drugs such as lipoic acid and MeB, which target the metabolism, decrease the redox shift by increasing catabolism
Nathan Goodyear

Ascorbic Acid Chemosensitizes Colorectal Cancer Cells and Synergistically Inhibits Tumo... - 0 views

www.ncbi.nlm.nih.gov/...PMC6064950

cancer vitamin C ascorbic acid colorectal cancer

shared by Nathan Goodyear on 26 Mar 22 - No Cached
  • therapeutic potential has been supported by a large and consistent body of evidences from in vitro
  • Ascorbic acid might act as a way to deliver hydrogen peroxide (H2O2) to the tissues
  • pharmacological concentrations of AA were capable of inducing anti-proliferative, cytotoxic and genotoxic effects
  • ...12 more annotations...
  • chemosensitizing
  • pharmacological concentrations of AA can sensitize cancer cells to chemotherapy, enhancing its antineoplastic effect
  • synergistic effect with conventional chemotherapeutic drugs is a fact already reported, in various types of cancer, by numerous authors, namely in pancreatic (Espey et al., 2011), prostate (Gilloteaux et al., 2014), lung (Lee et al., 2017), breast (Kurbacher et al., 1996; Wu et al., 2017) and ovarian (Ma et al., 2014) cancers.
  • chemosensitizing effect of vitamin C has already been proven by several authors in various types of cancer
  • intravenous pharmacological concentrations, may not only potentiate the effects of conventional chemotherapy, but also improve the quality of life of cancer patients
  • AA reinforced the anti-proliferative activity of 5-FU
  • Combined treatment induced a reduction of 11.5% and 43% in cell viability compared with AA or Iri therapies, respectively, emphasizing the synergistic effect
  • cytotoxic effect occurred with treatment with Iri alone, but also this effect was further potentiated by the presence of AA.
  • association of AA with Oxa showed very promising results, considering that a synergistic effect was demonstrated, in almost all conditions
  • AA and Oxa seem to act synergistically by the activation of the intrinsic pathway of apoptosis, translated on the statistically significant increase of the ratio between BAX and BCL-2 proteins, which in turn is associated with a decrease of Δψm
    • Nathan Goodyear
      Nathan Goodyear on 26 Mar 22
       
      Apoptosis -> decrease in mitochondrial membrane potential
  • Previous results obtained by our group showed that AA mediates reactive oxygen species (ROS) formation capable of irreparably damaging DNA
  • oxidative role of AA may be a key factor on the synergistic anti-cancer mechanism
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