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Nathan Goodyear

Favorable Outcome After Physiologic Dose of Sodium-d,l-3-Hydroxybutyrate in Severe MADD... - 0 views

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    high dose of ketone therapy via 3-HB ketone salt, in this case study, tolerated fine.  Most important, the higher, physiologic dose provided clinical improvement.
Nathan Goodyear

The physiological role of hormones in saliva. [Bioessays. 2009] - PubMed result - 0 views

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    The physiologic role of hormones in saliva
Nathan Goodyear

Nature vs. nurture: can exercise really alter fiber type composition in human skeletal ... - 0 views

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    Muscle fiber types exist on a continuum.
Nathan Goodyear

Vitamin C increases viral mimicry induced by 5-aza-2′-deoxycytidine | PNAS - 0 views

  • Vitamin C alone at concentrations up to 57 μM had little effect on cell growth but was toxic at 228 μM (SI Appendix, Fig. S1B), in line with recent studies of high vitamin C concentrations (125–2,000 μM)
  • In our combination approach, vitamin C increased the effects of low doses of 5-aza-CdR, with 57 μM vitamin C almost doubling the growth inhibition
  • Using the Chou–Talalay method (28), we found that the two compounds indeed acted synergistically, rather than additively, to inhibit cancer cell growth over the physiological ranges of vitamin C in healthy individuals (26–84 μM)
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  • These results show that targeting the cancer DNA methylome by combining low-dose 5-aza-CdR and vitamin C stimulates the expression of ERVs, the induction of a cell-autonomous immune activation response, and increased apoptosis of cancer cells
  • The addition of vitamin C to treatment protocols therefore may be a straightforward way to increase the clinical efficacy of such drugs in MDS and leukemia patients
  • Vitamin C deficiency has been seen previously in patients with multiple types of cancer, including hematological malignancies (35⇓–37). We predict that these patients might receive the most benefits from the combination treatment.
  • induction of an innate immune response
  • We therefore measured plasma concentrations of vitamin C in a small number of patients with miscellaneous hematologic malignancies. Strikingly, 58% of patients with hematological neoplasia who were not taking vitamin C supplements had severe vitamin C deficiency (serum concentration <11.4 μM, at which clinical features of scurvy may be manifested) (34), and 33% had vitamin C levels below the normal range
  • it is possible that vitamin C was oxidized to DHA before it was transported into the cells
  • Oral administration of vitamin C should be sufficient for the therapeutic strategy, because the concentrations reported in this study would not require i.v. administration.
    • Nathan Goodyear
       
      This statement lacks a basic understanding of vitamin C pharmacokinetics.
  • Vitamin C is an essential nutrient for humans and has been reported to increase IFN levels in human cells upon virus infection
  • daily treatment with vitamin C alone at physiological concentrations enhanced the expression of viral-defense genes relative to untreated cells
  • When combined with low-dose 5-aza-CdR, physiological concentrations of vitamin C synergistically inhibited cancer-cell growth and induced apoptosis. Such synergy was associated with increased ERV expression and dsRNA in treated cells. The mechanism of action differs from that of vitamin C at higher doses, which involves its pro-oxidant activity, including GSH inhibition, to generate reactive oxygen species
  • This activity has been shown to induce DNA damage and to enhance the sensitivities of myeloid malignancies, multiple myeloma, and cutaneous T-cell lymphoma to arsenic trioxide (41⇓⇓–44). It also can increase chemosensitivity of ovarian cancer cells (27) and selectively kill KRAS or BRAF mutant colorectal cancer cells by inhibiting GAPDH
  • reactive oxygen species
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    91% of patients with hematologic malignancies have vitamin C levels that are either low or severly deficient. This study found that vitamin C plus low dose DNA methyltransferase inhibitors have synergistic inhibition of cancer cell proliferation and increased apoptosis.  Unfortunately, the authors claimed that oral vitamin C would be sufficient which indicates an incredible lack of understanding of vitamin C pharmacokinetics.
Nathan Goodyear

Higher Free Thyroxine Levels Predict Increased Incidence of Dementia in Older Men: The ... - 0 views

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    what a silly study!  They look at free T4, the weakest thyroid hormone and found high levels to be associated with dementia.  However, they failed to assess free T3, the most biologically active, and reverse T3, inactive.  This study was like they intentionally blinded themselves of the body's physiology to study dementia.  This is the problem with a lot of research today: they have forgotten their foundation. Many older adults struggle with poor free T4 to free T3 conversion and high reverse T3 conversion.  So, without knowing what these clients were doing in these pathways makes their conclusion obsolete.
Nathan Goodyear

Update in TSH Receptor Agonists and Antagonists - 0 views

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    Just abstract is available to this just released article, but the opening sentence shows the importance of receptors: "the physiological role of the TSH receptor (TSHR) as a major regulator of thyroid functions is well understood..."
Nathan Goodyear

Interaction between a peroxisome proliferator-activated receptor γ gene polym... - 0 views

  • uniform dietary recommendations may not be appropriate for all individuals
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    Peroxisome proliferator-activated receptor gamma plays an important role in obesity and fat generation.  In this study, they showed how the genetic expression of different PPAR gamma genotypes results in altered physiologic response to fat intake in humans.  The interaction between genetics and the environment.
Nathan Goodyear

Thematic review series: The Pathogenesis of Atherosclerosis. An interpretive history of... - 0 views

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    great read on the underlying pathogenesis of atherosclerosis.  There is so much falsehood out there as it relates to the physiology behind atherosclerosis.  This reviews the biochemistry.
Nathan Goodyear

Effect of oral administration of testosterone on brachial arterial vasoreactivity in me... - 0 views

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    physiologic replacement of testosterone shown to increase NO synthesis, increased vasorelaxation, and reduced CVD symptoms, like hypertension.
Nathan Goodyear

Dehydroepiandrosterone in systemic lupus erythematosus - 0 views

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    DHEA therapy has provided benefit in autoimmune disease.  IN this study they review the previous articles and physiology behind DHEA's proposed benefit in autoimmune disease.
Nathan Goodyear

The endocrinology of sexual arousal - 0 views

  • A number of age-related changes may be relevant: altered negative feedback of testosterone and hence less increase in luteinizing hormone (LH) with falling testosterone levels, increased sex hormone binding globulin (SHBG) and hence relatively reduced free testosterone and the likelihood of an age-related decline in testosterone receptor sensitivity
  • In the older male, the picture is complicated by various aging effects, including altered hypothalamo–pituitary feedback, increased testosterone binding and reduced receptor sensitivity
  • The neurophysiological basis of NPT is still disputed, but one plausible explanation is that REM sleep is associated with a ‘switching off’ of the noradrenergic cells in the locus coeruleus
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  • the impact of testosterone on the emergence of sexual arousability is less clear
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    Good discussion of the arousal/sexual response differences between men and women from a physiological perspective.  
Nathan Goodyear

Metabolic management of brain cancer - 0 views

  • Glutamine is a major metabolic fuel for both brain tumor cells and tumor-associated macrophages (TAMs)
  • the malignant phenotype of brain tumor cells that survive radiotherapy is often greater than that of the cells from the original tumor.
  • Conventional chemotherapy has faired little better than radiation therapy for the long-term management of malignant brain cancer
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  • most conventional radiation and brain cancer chemotherapies can enhance glioma energy metabolism and invasive properties, which would contribute to tumor recurrence and reduced patient survival [34].
  • We contend that all cancer regardless of tissue or cellular origin is a disease of abnormal energy metabolism
  • complex disease phenotypes can be managed through self-organizing networks that display system wide dynamics involving oxidative and non-oxidative (substrate level) phosphorylation
  • As long as brain tumors are provided a physiological environment conducive for their energy needs they will survive; when this environment is restricted or abruptly changed they will either grow slower, growth arrest, or perish [8] and [19]
  • New information also suggests that ketones are toxic to some human tumor cells and that ketones and ketogenic diets might restrict availability of glutamine to tumor cells [68], [69] and [70].
  • The success in dealing with environmental stress and disease is therefore dependent on the integrated action of all cells in the organism
  • Tumor cells survive in hypoxic environments not because they have inherited genes making them more fit or adaptable than normal cells, but because they have damaged mitochondria and have thus acquired the ability to derive energy largely through substrate level phosphorylation
  • Cancer cells survive and multiply only in physiological environments that provide fuels (mostly glucose and glutamine) subserving their requirement for substrate level phosphorylation
  • Integrity of the inner mitochondrial membrane is necessary for ketone body metabolism since β-hydroxybutyrate dehydrogenase, which catalyzes the first step in the metabolism of β-OHB to acetoacetate, interacts with cardiolipin and other phospholipids in the inner membrane
  • the mitochondria of many gliomas and most tumors for that matter are dysfunctional
  • Cardiolipin is essential for efficient oxidative energy production and mitochondrial function
  • Any genetic or environmental alteration in the content or composition of cardiolipin will compromise energy production through oxidative phosphorylation
  • The Crabtree effect involves the inhibition of respiration by high levels of glucose
  • the Warburg effect involves elevated glycolysis from impaired oxidative phosphorylation
  • the Crabtree effect can be reversible, the Warburg effect is largely irreversible because its origin is with permanently damaged mitochondria
  • The continued production of lactic acid in the presence of oxygen is the metabolic hallmark of most cancers and is referred to as aerobic glycolysis or the Warburg effect
  • We recently described how the retrograde signaling system could induce changes in oncogenes and tumor suppressor genes to facilitate tumor cell survival following mitochondrial damage [48].
  • In addition to glycolysis, glutamine can also increase ATP production under hypoxic conditions through substrate level phosphorylation in the TCA cycle after its metabolism to α-ketoglutarate
  • mitochondrial lipid abnormalities, which alter electron transport activities, can account in large part for the Warburg effect
  • targeting both glucose and glutamine metabolism could be effective for managing most cancers including brain cancer
  • The bulk of experimental evidence indicates that mitochondria are dysfunctional in tumors and incapable of generating sufficient ATP through oxidative phosphorylation
  • Cardiolipin defects in tumor cells are also associated with reduced activities of several enzymes of the mitochondrial electron transport chain making it unlikely that tumor cells with cardiolipin abnormalities can generate adequate energy through oxidative phosphorylation
  • The Crabtree effect involves the inhibition of respiration by high levels of glucose
  • Warburg effect involves elevated glycolysis from impaired oxidative phosphorylation
  • TCA cycle substrate level phosphorylation could therefore become another source of ATP production in tumor cells with impairments in oxidative phosphorylation
  • Caloric restriction, which lowers glucose and elevates ketone bodies [63] and [64], improves mitochondrial respiratory function and glutathione redox state in normal cells
  • DR naturally inhibits glycolysis and tumor growth by lowering circulating glucose levels, while at the same time, enhancing the health and vitality of normal cells and tissues through ketone body metabolism
  • DR is anti-angiogenic
  • DR also reduces angiogenesis in prostate and breast cancer
  • We suggest that apoptosis resistance arises largely from enhanced substrate level phosphorylation of tumor cells and to the genes associated with elevated glycolysis and glutaminolysis, e.g., c-Myc, Hif-1a, etc, which inhibit apoptosis
  • Modern medicine has not looked favorably on diet therapies for managing complex diseases especially when well-established procedures for acceptable clinical practice are available, regardless of how ineffective these procedures might be in managing the disease
  • More than 60 years of clinical research indicates that such approaches are largely ineffective in extending survival or improving quality of life
  • The process is rooted in the well-established scientific principle that tumor cells are largely dependent on substrate level phosphorylation for their survival and growth
  • Glucose and glutamine drive substrate level phosphorylation
  • targeting the glycolytically active tumor cells that produce pro-cachexia molecules, restricted diet therapies can potentially reduce tumor cachexia
  • It is important to recognize, however, that “more is not better” with respect to the ketogenic diet
  • Blood glucose ranges between 3.0 and 3.5 mM (55–65 mg/dl) and β-OHB ranges between 4 and 7 mM should be effective for tumor management
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    Dr Seyfriend presents his metabolic approach to the treatment of brain cancer.
Nathan Goodyear

Chapter 8: Estrogen Receptor-Mediated Processes in Normal and Cancer Cells - 0 views

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    review of estrogen receptors and their role in normal physiology and cancer.
Nathan Goodyear

Fatigue and underperformance in athletes: the overtraining syndrome - 0 views

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    Good review of the physiology behind over training syndrome.
Nathan Goodyear

Testosterone: a vascular hormone in health and disease - 0 views

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    testosterone therapy has tremendous cardiovascular benefit in men with low T.  The key here is physiologic replacement of Testosterone.  Testosterone is a vasodilator and anti-inflammatory agent in men with low T.  Testosterone therapy improves cardiac function in those with DHF and angina.  Testosterone is found to be a Ca++ channel blocker--anyone say hypertension treatment?
Nathan Goodyear

Risk Factors Associated With Cardiovascular Events During Testosterone Administration i... - 0 views

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    This study proves the problems rampant in science today.  This study looked at older men with mobility limitations: safe to say, not optimal health.  They give 10 grams of testosterone daily to these men.  Physiologic doses are 5-10 mg.  And they are surprise that there is an increase in side effects, here in this study CVD.  They did look at cytokines, I'll give them that; but they did not look at aromatase activity and E2, E1 levels which have been shown to be the driving forces behind these inflammatory cytokines in men.  Testosterone has in fact been shown to downregulate these inflammatory cytokines.  Poor study.  No conclusion can be taken from this study.
wheelchairindia

Pediatric Wheelchair - 0 views

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    The body size differences are paralleled by maturational changes. The smaller body of an infant or neonate is substantially different physiologically from that of an adult. Congenital defects, genetic variance, and developmental issues are of greater concern to pediatricians than they often are to adult physicians. A major difference between pediatrics and adult medicine is that children are minors and, in most jurisdictions, cannot make decisions for themselves. The issues of guardianship, privacy, legal responsibility and informed consent must always be considered in every pediatric procedure. In a sense, pediatricians often have to treat the parents and sometimes, the family, rather than just the child. Adolescents are in their own legal class, having rights to their own health care decisions in certain circumstances. In basic terms, pediatricians take care of all of the children's needs from emotional support to medical support. Wheelchair india as Pediatric Wheelchair Manufacturers and Pediatric Wheelchair supplier sale at low cost - price, We Sale online Pediatric Powered Wheelchair and Pediatric Electric Wheelchair at wholesale prices...
Nathan Goodyear

Stressed Memories: How Acute Stress Affects Memory Formation in Humans - 0 views

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    good article on how acute, short term stress, effects memory.  Stress is a real physiologic response with real effects.
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