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Nathan Goodyear

Progesterone metabolites in breast cancer - 1 views

erc.endocrinology-journals.org/...717.full

progesterone metabolism tumor tumorigenesis cancer risk growth hormone hormones 5-beta-pregnanediol 5-alpha-pregnanediol 4-pregnenediol 5-alpha reductase

shared by Nathan Goodyear on 20 Feb 12 - No Cached
  • P metabolites produced within breast tissues might be independently active hormones functioning as cancer-promoting or -inhibiting regulatory agents
  • these P metabolites function as independent pro-or anti-cancer autocrine/paracrine hormones that regulate cell proliferation, adhesion, apoptosis and cytoskeletal, and other cell status molecules via novel receptors located in the cell membrane and intrinsically linked to cell signaling pathways
  • only a fraction of all breast cancer patients respond to this estrogen-based therapy and the response is only temporary
  • ...30 more annotations...
  • P serves as the precursor for the major steroid hormones (androgens, estrogens, corticosteroids) produced by the gonadal and adrenal cortical tissues.
  • 5α-pregnane, 5β-pregnane, and 4-pregnene metabolites of P
  • These P-metabolizing enzymes included 5α-reductase, 5β-reductase, 3α-hydroxysteroid oxido-reductase (3α-HSO), 3β-HSO, 20α-HSO, 20β-HSO, 6α(β)-, 11β-, 17-, and 21-hydroxylase, and C17–20-lyase
  • Reduction of P to 5α-pregnanes is catalyzed by 5α-reductase and the direct 5α-reduced metabolite of P is 5α-pregnane-3,20-dione (5αP). The 5α-reductase reaction is irreversible
  • The two 4-pregnenes resulting from direct P conversion are 4-pregnen-3α-ol-20-one (3αHP) and 4-pregnen-20α-ol-3-one (20αHP), catalyzed by the actions of 3α-HSO and 20α-HSO respectively
  • the P-metabolizing enzyme activities identified in human breast tissues and cell lines were: 5α-reductase, 3α-HSO, 3β-HSO, 20α-HSO, and 6α-hydroxylase
  • In normal breast tissue, conversion to 4-pregnenes greatly exceeded the conversion to 5α-pregnanes, whereas in tumorous tissue, conversion to 5α-pregnanes greatly exceeded that to 4-pregnenes
  • The results indicated that P 5α-reductase activity is significantly higher, whereas P 3α-HSO and 20α-HSO activities are significantly lower in tumor than in normal tissues
  • he results showed that production of 5α-pregnanes was higher and that of 4-pregnenes was lower in tumorigenic (e.g. MCF-7) than in nontumorigenic (e.g. MCF-10A) cells (Fig. 3c⇑), while differences in ER/P status did not appear to play a role
  • The 5α-pregnane-to-4-pregnene ratios were 7- to 20-fold higher in the tumorigenic than in the nontumorigenic cell lines
  • altered direction in P metabolism, and hence in metabolite ratios, was due to significantly elevated 5α-reductase and depressed 3α- and 20α-HSO activities in breast tumor tissues and tumorigenic cells. It appeared, therefore, that changes in P-metabolizing enzyme activities might be related to the shift toward mammary cell tumorigenicity and neoplasia
  • In vivo, changes in enzyme activity can result from changes in levels of the enzyme due to changes in expression of the mRNA coding for the enzyme, or from changes in the milieu in which the enzyme operates (such as temperature and pH, and concentrations of cofactors, substrates, products, competitors, ions, phospholipids, and other molecules)
  • Overall, the enzyme activity and expression studies strongly suggest that 5α-reductase stimulation and 3α- and 20α-HSO suppression are associated with the transition from normalcy to cancer of the breast
  • The level of expression of 5α-reductase is up-regulated by estradiol and P in the uterus (Minjarez et al. 2001) and by 5α-dihydrotestosterone (DHT) in the prostate
  • 3αHP inhibited whereas 5αP-stimulated proliferation
  • Stimulation in cell numbers was also observed when cells were treated with other 5α-pregnanes, such as 5α-pregnan-3α-ol-20-one, 5α-pregnan-20α-ol-3-one, and 5α-pregnane-3α,20α-diol, whereas other 4-pregnenes such as 20α-HP and 4-pregnene-3α,20α-diol resulted in suppression of cell proliferation
  • Stimulation of cell proliferation with 5αP and inhibition with 3αHP were also observed in all other breast cell lines examined, whether ER/P-negative (MCF-10A, MDA-MB-231) or ER/P-positive (T47D, ZR-75-1) and whether requiring estrogen for tumorigenicity (MCF-7, T47D) or not (MDA-MB-231), or whether they are nontumorigenic (
  • αHP resulted in significant increases in apoptosis and decreases in mitosis, leading to significant decreases in total cell numbers. In contrast, treatment with 5αP resulted in decreases in apoptosis and increases in mitosis.
  • The opposing actions of 5αP and 3αHP on both cell anchorage and proliferation strengthen the hypothesis that the direction of P metabolism in vivo toward higher 5α-pregnane and lower 4-pregnene concentrations could promote breast neoplasia and lead to malignancy.
  • he effects on proliferation and adhesion were not due to P, but due to the 5α-reduced metabolites
  • The studies showed that binding of 5αP or 3αHP occurs in the plasma membrane fractions, but not in the nuclear or cytosolic compartments
  • separate high-specificity, high-affinity, low- capacity receptors for 5αP and 3αHP that are distinct from each other and from the well-studied nuclear/cytosolic P, estrogen, and androgen and corticosteroid receptors
  • The studies thus provided the first demonstration of the existence of specific P metabolite receptors
  • the receptor results suggest that the putative tumorigenic actions of 5αP may be significantly augmented by the estradiol-induced increases in 5αP binding and decreases in 3αHP binding.
  • Estradiol and 5αP resulted in significant dose-dependent increases, whereas 3αHP and 20αHP each resulted in dose-dependent decreases in total ER
  • In combination, estradiol + 5αP or 3αHP + 20αHP resulted in additive increases or decreases respectively in ER numbers.
  • The data suggest that the action of 5αP on breast cancer cells involves modulation of the MAPK signaling pathway
  • current evidence does not appear to support the notion that increased 5α-reductase activity/ expression might significantly alter androgen influences on breast tumor growth.
  • both testosterone and DHT inhibit cell growth more or less to the same extent
  • Note that 5α-reductase reaction is not reversible
  • Nathan Goodyear on 20 Feb 12
     
    Fantastic read on the effects of progesterone metabolism on tumor and cancer growth.  Tumorigenesis is not just about the hormone, hormone balance, but about the metabolism of hormones.  This is why premarin is so carcinogenic: it is primarily metabolized by the 4-OH estrone pathway.
Edgar Anderson

Highly Competent Dieticians - 1 views

started by Edgar Anderson on 27 Feb 13 no follow-up yet
Nathan Goodyear

The Ketogenic Diet and Sport: A Possible Marriage? : Exercise and Sport Sciences Reviews - 0 views

journals.lww.com/..._and_Sport___A_Possible.8.aspx

nutrition diet ketogenic ketogenic diet sports athletes exercise sports medicine

shared by Nathan Goodyear on 16 Nov 16 - No Cached
  • It is important to note that, although the blood level of glucose drops, it still remains at a physiological level (23), which is maintained through gluconeogenesis involving glucogenic amino acids and also glycerol released from triglycerides
  • “physiological ketosis” where KB levels may rise to 7 to 8 mmol L-1 (but without any pH change). In “pathological diabetic ketoacidosis,” on the other hand, ketonemia can exceed 20 mmol L-1 and also cause lowering of blood pH
  • in the initial phase of KD, about 16% of glucose comes from glycerol (released from triglyceride hydrolysis) and the bulk (60–65 g) from proteins via gluconeogenesis (proteins may be of either dietary or endogenous origin
  • ...5 more annotations...
  • the protein supply consumed during a KD “preserves,” as demonstrated, lean body mass
  • The importance of glycerol as a glucose source increases progressively during ketosis; in fact, glycerol passes from supplying 16% of total glucose to an average of 60% after many days (>7 d) of complete fasting (from 38% in lean individual to 79% in the obese).
  • The possible reasons for the effectiveness of KD for weight loss may be listed as follows, in order of evidence, strongest first: Figure 3Image Tools 1. Appetite reduction: protein satiety, effects on appetite-related hormones such as ghrelin, and possibly a sort of direct appetite-blocking effect of KB 2. Reduced lipogenesis and increased fat oxidation 3. A reduction in respiratory quotient may indicate a greater metabolic efficiency in fat oxidation 4. A thermic effect of proteins and increased energy usage by gluconeogenesis
  • all data regarding biochemical and molecular mechanisms suggest that it is very difficult to increase muscle mass during a KD; use of which really should be limited to the few days immediately before competition in bodybuilding.
  • a long-term KD can interfere with some muscle hypertrophy mechanisms and this could be counterproductive if the aim of the athlete is to gain muscle mass
  • Nathan Goodyear on 16 Nov 16
     
    Great read on the ketogenic  and its application to sports/training...
Nathan Goodyear

Thieme E-Journals - Hormone and Metabolic Research / Abstract - 0 views

www.thieme-connect.com/...DOI

hormone hormones estradiol pancreatic cancer

shared by Nathan Goodyear on 17 Sep 13 - No Cached
  • Nathan Goodyear on 17 Sep 13
     
    small study, but males with pancreatic cancer were found to have higher levels of FSH (p < 0.01), LH and oestradiol (p < 0.001) and lower levels of progesterone (p < 0.01) and testosterone (p < 0.05) than the controls. Female patients with pancreatic cancer were found to have higher levels of oestradiol (p < 0.001) and lower levels of LH, FSH and progesterone.  Though cause and effect is not known, the expression of ER alpha in pancreatic cancer is known and the inflammatory and pro-growth signal of ER alpha is known, thus heavy stimulation would be unwise.
Nathan Goodyear

Influences of percutaneous administration of estra... [Fertil Steril. 1995] - PubMed re... - 0 views

www.ncbi.nlm.nih.gov/...7890063

Progesterone Estradiol breast cancer BHRT bioidentical hormones

shared by Nathan Goodyear on 07 Nov 10 - No Cached
  • Increased P concentration significantly decreases the number of cycling epithelial cells.
  • CONCLUSION: Exposure to P for 10 to 13 days reduces E2-induced proliferation of normal breast epithelial cells in vivo.
  • Nathan Goodyear on 07 Nov 10
     
    Progesterone reduces Estradiol breast cell growth
Nathan Goodyear

Beneficial effects of a long-term oral L-arginine treatment added to a hypocaloric diet... - 0 views

ajpendo.physiology.org/...E906.full

L-Arginine weight loss diet overweight obesity insulin-resistant diabetic patients

shared by Nathan Goodyear on 09 Jul 11 - No Cached
  • L-arginine supplementation further decreased FM (P &lt; 0.05) and waist circumference (P &lt; 0.0001), preserving FFM (P &lt; 0.03), and improved mean daily glucose profiles (P &lt; 0.0001) and fructosamine (P &lt; 0.03). Moreover, change in area under the curve of cGMP (second messenger of nitric oxide; P &lt; 0.001), superoxide dismutase (index of antioxidant capacity; P &lt; 0.01), and adiponectin levels (P &lt; 0.02) increased, whereas basal endothelin-1 levels (P &lt; 0.01) and leptin-to-adiponectin ratio (P &lt; 0.05) decreased in the L-arginine group.
  • Nathan Goodyear on 09 Jul 11
     
    L-Arginine helps to preserve muscle, while increase fat loss.  This will help to prevent fat rebound in weight loss programs.  Additionally, insulin resistance improved.
medicraft

Automated medical billing software - 0 views

Automated medical billing software streamlines the billing process, reducing errors and administrative burdens. By automating tasks like claims submission and payment tracking, healthcare providers...

Automated medical billing software

started by medicraft on 21 Feb 25 no follow-up yet
Nathan Goodyear

'Spikeopathy': COVID-19 Spike Protein Is Pathogenic, from Both Virus and Vaccine mRNA -... - 0 views

europepmc.org/...PMC10452662

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

shared by Nathan Goodyear on 01 Sep 23 - No Cached
  • toxicity of the spike protein—both from the virus and also when produced by gene codes in the novel COVID-19 mRNA and adenovectorDNA vaccines
  • ‘spikeopathy’;
  • A central issue has been growing evidence of pathogenic effects of the SARS-CoV-2 spike protein—whether as part of the virus or produced by genetic codes in the mRNA and adenovectorDNA vaccines
  • ...10 more annotations...
  • It is apparent that the original Wuhan strain and early variants of SARS-CoV-2 in 2020 were more pathogenic than later variants. This is consistent with typical viral adaptive evolution to more infectious but less pathogenic strains, a natural phenomenon
  • SARS-CoV-2 spike protein is pathogenic, whether from the virus or created from genetic code in mRNA and adenovectorDNA vaccines.
  • Evidence suggests reverse transcription of mRNA into a DNA copy is possible
  • further suggests the possibility of intergenerational transmission if germline cells incorporate the DNA copy into the host genome
    • Nathan Goodyear
      Nathan Goodyear on 01 Sep 23
       
      Intergenerational and transgenerational!
  • (‘spikeopathy’) via several mechanisms that lead to inflammation, thrombogenesis, and endotheliitis-related tissue damage
  • Interaction of the vaccine-encoded spike protein with ACE-2, P53 and BRCA1 suggests a wide range of possible biological interference with oncological potential
  • Repeated COVID-19 vaccine booster doses appear to induce tolerance and may contribute to recurrent COVID-19 infection and ‘long COVID’.
  • spike protein is not only toxic through binding of ACE-2 receptors
  • interaction with cancer suppressor genes BRCA and P53
  • mitochondrial damage
medicraft

Fast &amp; Secure Medical Billing Software - 0 views

Unify Medicraft provides the leading medical billing software system for clinics and hospitals along with their solution.&nbsp;Our simple platform helps speed up claim processing and error reductio...

medical billing

started by medicraft on 29 Jan 25 no follow-up yet
medicraft

Scheduling Software Improves Patient Experience - 0 views

With patient scheduling software, booking an appointment becomes simple - even for those who do not speak English. It says, patients can choose when to come, saving time and effort. This software a...

medical billing software

started by medicraft on 06 Feb 25 no follow-up yet
medicraft

How Expert Services Can Help You to Simplify Your Billing Process - 0 views

Medical billing is a complicated process that makes it even hard for small practitioners to accomplish. Unify medicraft provide correct coding and claims' denial, early submission of claims. This r...

medical billing

started by medicraft on 17 Jan 25 no follow-up yet
Nathan Goodyear

Chorionic Gonadotropin in Weight Control, November 29, 1976, Young et al. 236 (22): 249... - 0 views

jama.ama-assn.org/...2495.short

HCG human chorionic gonadotropin

shared by Nathan Goodyear on 21 Apr 11 - No Cached
  • There was no statistically significant difference between those receiving HCG vs placebo during any phase of this study (P&gt;.1).
  • Nathan Goodyear on 21 Apr 11
     
    ditto: HCG no better than placebo in weight loss
Nathan Goodyear

Inborn-like errors of metabolism are determinants of breast cancer risk, clinical respo... - 0 views

www.ncbi.nlm.nih.gov/...PMC6114970

cancer metabolism breast cancer glutamine glutamate aspartate oncogenes

shared by Nathan Goodyear on 24 Sep 18 - No Cached
  • We now recognize that human cancers evolve in an environment of metabolic stress. Rapidly proliferating tumor cells deprived of adequate oxygen, nutrients, hormones and growth factors up-regulate pathways that address these deficiencies to overcome hypoxia (HIF), vascular insufficiency (VEGF), growth factor deprivation (EGFR, HER2) and the loss of hormonal support (ER, PR, AR) all to enhance survival and proliferation
  • RAS, PI3K, TP53 and MYC
  • The results suggest that breast cancer could be preceded by systemic subclinical disturbances in glucose-insulin homeostasis characterized by mild, likely asymptomatic, IEM-like biochemical changes
  • ...16 more annotations...
  • The process would include variable periods of hyperinsulinemia with the consequent systemic MYC activation of glycolysis, glutaminolysis, structural lipidogenesis and further exacerbation of hypoglycemia, the result of MYC's known role as an inhibitor of liver gluconeogenesis
  • The metabolic changes we describe in breast cancer arise in concert with IEM-like changes in oxidative phosphorylation as detected by increased values of the ratio lactate/pyruvate (Supplementary Table 2A, 2B) characteristic of Ox/Phos deficiency [25]. In our study, 76% (70/92) of the European breast cancer patients had lactate/pyruvate ratios values higher than the normal value of 25.8
  • four-fold higher frequency of cancer (including breast) in patients with energy metabolism disorders
  • growing recognition that cancer cells differ from their normal counterparts in their use of nutrients, synthesis of biomolecules and generation of energy
  • glutamine concentrations in the cancer patients were reduced to nearly 1/8 of the levels observed in the normal population
  • blood concentrations of aspartate (p = 1.7e-67, FDR = 8.3e-67) (Figure ​(Figure1E)1E) and glutamate (p = 6.4e-96, FDR = 6.2e-95) (Figure ​(Figure1F)1F) were nearly 10 fold higher than the normal ranges of 0–5 μM/L and 40 μM/L, respectively
  • glutamine consumption associated with parallel increases in glutamate and aspartate (Figure ​(Figure1A1A red arrows) is considered a hallmark of MYC-driven “glutaminolysis”
  • Gln/Glu ratio inversely correlates with i- late stage metabolic syndrome and with ii- increased chance of death
  • changes in glutamine consumption, reflected by the Gln/Glu ratio could provide a metabolic link between breast cancer initiation and diabetes, reflective of a systemic metabolic reprogramming from glucose to glutamine as the preferred source of precursors for biosynthetic reactions and cellular energy
  • lower Gln/Glu ratios inversely correlated with insulin resistance and the risk of diabetes
  • the metabolic dependencies of cancer characterized by excessive glycolysis, glutaminolysis and malignant lipidogenesis, previously considered a consequence of local tumor DNA aberration [23] could, instead, represent a systemic biochemical aberration that predates and very likely promotes tumorigenesis
  • these metabolic disturbances would be expected to remain extant after therapeutic interventions
  • accumulation of very long chain acylcarnitines such as C14:1-OH (p = 0.0, FDR = 0.0), C16 (p = 0.0, FDR = 0.0), C18 (p = 0.0, FDR = 0.0) and C18:1 (p = 1.73e-322, FDR = 1.16-321) and lipids containing VLCFA (lysoPC a C28:0) (p = 1.14-e95, FDR = 1.65e-95) in the blood of breast and colon cancer patients
  • Among the most powerful metabolic equations for MYC-activation is that which links the widely used MYC-driven desaturation marker ratio of SFA/MUFA to the MYC glutaminolysis-associated ratio of (Asp/Gln)
  • liver dysfunction shares many features with both IEM and cancer suggesting a role for hepatic dysfunction in carcinogenesis
  • cancer “conscripts” the human genome to meet its needs under conditions of systemic metabolic stress
  • Nathan Goodyear on 24 Sep 18
     
    Breast cancer is a metabolic disease.  Now, where have I heard that cancer is a metabolic disease?
Nathan Goodyear

PLOS ONE: Increased Risk of Non-Fatal Myocardial Infarction Following Testosterone Ther... - 0 views

www.plosone.org/...10.1371%2Fjournal.pone.0085805

Testosterone therapy cardiovascular disease men male hormones

shared by Nathan Goodyear on 30 Jan 14 - No Cached
  • For all TT prescription subjects combined, the post/pre prescription rate ratio for MI (RR)was 1.36
  • In men aged 65 years and older the RR was 2.19 (1.27, 3.77), while in men under age 65 years the RR was 1.17
  • increasing RR with increasing age.
  • ...20 more annotations...
  • The RRs were 0.95 (0.54, 1.67) under 55 years
  • 1.35 (0.77, 2.38) at 55–59
  • 1.29 (0.71, 2.35) at 60–64,
  • 1.35 (0.44, 4.18) at 65–69, 1.62
  • 3.43 (1.54, 7.66) at 75 years and older
  • The adjusted post/pre RR for PDE5I across all ages was 1.08
  • For TT prescription, in men under age 65 years, the RR was 2.90 (1.49, 5.62) for those with a history of heart disease and 0.90 (0.61, 1.34) for those without
  • In men aged 65 year and older, the RR was 2.16 (0.92, 5.10) for those with a history of heart disease and 2.21 (1.09, 4.45) for those without.
  • Among men aged 65 years and older, we observed a two-fold increase in the risk of MI in the 90 days after filling an initial TT prescription
  • Among younger men with a history of heart disease, we observed a two to three-fold increased risk of MI in the 90 days following an initial TT prescription and no excess risk in younger men without such a history
  • Among older men, the two-fold increased risk was associated with TT prescription regardless of cardiovascular disease history
  • our own findings appear consistent with a higher frequency of thrombotic events following TT prescription among men with more extensive coronary vascular disease.
  • Our findings are consistent with a recent meta-analysis of placebo-controlled randomized trials of testosterone therapy lasting 12 or more weeks among mainly older men, which reported that testosterone therapy increased the risk of adverse cardiovascular-related events (OR = 1.54, 95%CI:1.09, 2.18), as well as serious adverse cardiovascular-related events (OR = 1.61, 95%CI:1.01, 2.56) which included myocardial infarction along with other conditions
  • This association appeared unrelated to average baseline testosterone level (p = 0.70) but varied by source of funding (p = 0.03), with a stronger summary effect in a meta-analysis of studies not funded by the pharmaceutical industry (OR = 2.06, 95%CI:1.34, 3.17) compared with studies funded by the pharmaceutical industry
    • Nathan Goodyear
      Nathan Goodyear on 30 Jan 14
       
      This supports prior analysis that studies done by pharmaceutical corps will be more favorable to their product(s) than those independently funded.  This is called bias.
  • the evidence supports an association between testosterone therapy and risk of serious, adverse cardiovascular-related events–including non-fatal myocardial infarction–in men
  • there is some evidence that low endogenous testosterone levels may also be positively associated with cardiovascular events
  • effects of endogenous and exogenous testosterone may differ. Exogenous testosterone (TT) is associated with physiologic changes that predispose to clotting and thrombotic disorders including increased blood pressure [18], polycythemia [19], reductions in HDL cholesterol [18], [20], and hyperviscosity of the blood and platelet aggregation. [20]–[23]; TT also increases circulating estrogens [24], [25] which may play a role in the observed excess of adverse cardiovascular-related events, given that estrogen therapy has been associated with this excess in both men and women
  • did not include information on the serologic or diagnostic indications for treatment.
  • no association between PDE5I prescriptions and the risk of MI
  • Recently TT has been increasing extraordinarily rapidly, including among younger men and among those without hormone measurement
  • Nathan Goodyear on 30 Jan 14
     
    New cohort study finds increased risk of Testosterone in men > 65 and those : these are based in marketing-based medicine not evidence based medicine.
felipp windsor

Thank You The Dental Co. - 1 views

I really got worried when I found out that I got some tooth problems. For one thing, I have low tolerance to pain and I do not want to lose any of my teeth. That is why I looked for the best dentis...

teeth whitening windsor

started by felipp windsor on 03 Dec 13 no follow-up yet
felipp windsor

Restoring My Daughter's Shiny White Teeth - 1 views

I was surprised when I noticed that the teeth of my 13 year -old- daughter were discoloured. They were no longer that shiny and that white anymore. Maybe it was because of the food that she eats ev...

teeth whitening windsor

started by felipp windsor on 05 Dec 13 no follow-up yet
felipp windsor

Restoring My Daughter's Shiny White Teeth - 1 views

I was surprised when I noticed that the teeth of my 13 year -old- daughter were discoloured. They were no longer that shiny and that white anymore. Maybe it was because of the food that she eats ev...

teeth whitening windsor

started by felipp windsor on 31 Oct 13 no follow-up yet
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