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Nathan Goodyear

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

  • 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
       
      Wow
    • Nathan Goodyear
       
      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
       
      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
       
      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
fitspresso

https://www.fitspresso-co.com/ - 0 views

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    FitSpresso™ | Official Site fitspresso-co.com FitSpresso Only $39/Bottle Limited Time Offer! FitSpresso Special Deal + Special 51% Discount Save $660 + 180 Days Money Back Guarantee FitSpresso Herpesyl Five Star A dietary product formulated to assist users in reducing weight can increase other advantages that can support overall health. This product can assist users in getting closer to the desirable body weight. Regular Price: 149/per bottle Only for: $39/per bottle Buy Now What IsFitSpresso? FitSpresso is promoted as a natural supplement that comes in the form of diet pills, and it can aid in rapid and efficient weight loss, similar to many other supplements. The term "natural supplements refers to a nutritional supplement that is made entirely of natural, chemical-free materials. You can utilize these organic ingredients to aid in natural weight loss. It can speed up your body's metabolism and assist with other crucial processes. All parts of our bodies are impacted by weight increase, and not only do we need to deal with the increased weight, but we also need to deal with the numerous problems and illnesses that come along with it. This refers to the risk of developing chronic cardiac conditions, low blood pressure, and, in some circumstances, problems with blood sugar. However, FitSpresso even with its bright and bold claims, can help you efficiently manage your weight and completely avoid these extra uncomfortable problems. FitSpresso is a supplement that comes in the form of a pill, which makes it tasty, simple to swallow, and handy. According to the manufacturer, these diet tablets are GMO-free and toxic-free, making them edible. This is why we have things such as weight loss supplements. Thanks to modern advancements, we can just take a dietary supplement pill to bring about significant weight loss in a completely healthy and natural manner. Not only this, but dietary supplements can also support healthy blood sugar levels and help with
brandnew12

Home Remedies: Longevity Tips - Kindle edition by John Okeniyi. Health, Fitness & D... - 0 views

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    Are you struggling with the fact that you really don't know anything about how to get into shape? If you're busy living in yesterday's errors, many of your decisions will be founded on guilt and shame instead of what you really want (and need) to accomplish to achieve your goals. Real change comes from day-to-day choices and becoming mindful and basing your choices on what you need now (rather than what you did or didn't do yesterday) will make your exercise life much more passable. What if I can offer you a solution that will help you to attain greatness, to become a success and learn about the best ways to get in shape? In this book, you will learn about: - Navigate the Astral Plane - MIRROR MADNESS - The Health Zen - Vitamin Vitality - Native American Healing - Boost your Health with Gua Sha - Beautiful Body Essential - Secret of Food Combination - Lose Weight Fasting - Child Diet - many other useful things!
  •  
    Are you struggling with the fact that you really don't know anything about how to get into shape? If you're busy living in yesterday's errors, many of your decisions will be founded on guilt and shame instead of what you really want (and need) to accomplish to achieve your goals. Real change comes from day-to-day choices and becoming mindful and basing your choices on what you need now (rather than what you did or didn't do yesterday) will make your exercise life much more passable. What if I can offer you a solution that will help you to attain greatness, to become a success and learn about the best ways to get in shape? In this book, you will learn about: - Navigate the Astral Plane - MIRROR MADNESS - The Health Zen - Vitamin Vitality - Native American Healing - Boost your Health with Gua Sha - Beautiful Body Essential - Secret of Food Combination - Lose Weight Fasting - Child Diet - many other useful things!
  •  
    Are you struggling with the fact that you really don't know anything about how to get into shape? If you're busy living in yesterday's errors, many of your decisions will be founded on guilt and shame instead of what you really want (and need) to accomplish to achieve your goals. Real change comes from day-to-day choices and becoming mindful and basing your choices on what you need now (rather than what you did or didn't do yesterday) will make your exercise life much more passable. What if I can offer you a solution that will help you to attain greatness, to become a success and learn about the best ways to get in shape? In this book, you will learn about: - Navigate the Astral Plane - MIRROR MADNESS - The Health Zen - Vitamin Vitality - Native American Healing - Boost your Health with Gua Sha - Beautiful Body Essential - Secret of Food Combination - Lose Weight Fasting - Child Diet - many other useful things!
Nathan Goodyear

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

  • 15%–20%
  • key mediator of cell growth, differentiation, and survival
  • of higher histological grade and are more likely to invade axillary lymph nodes
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  • 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
       
      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
       
      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
       
      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
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    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.
fitspresso

https://www.sightcare-co.com/ - 0 views

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    Sight Care | Official Site sightcare-co.com · by Sight Care Sight Care Only $49/Bottle Limited Time Offer! Sight Care Special Deal + Special 67% Discount Save $600 + 180 Days Money Back Guarantee #1.The Sight Care vision supplement is a dietary supplement for helping you improve your vision and brain health. Sight Care eye supplements are formulated to provide a synergistic blend of vitamins, minerals, antioxidants, and other bioactive compounds that are essential for maintaining healthy vision Regular Price: 147/per bottle Only for: $49/per bottle What Is Sight Care? This powerful vision support supplement is made with a unique blend of natural ingredients and plant extracts that work together synergistically to deliver numerous benefits for your brain and eye health. With Sight Care, you can expect to experience increased energy levels, improved eyesight, and an overall revitalized sense of well-being. Taking care of your vision health is not just about seeing clearly; it's also about maintaining your overall brain health. As we age, our vision deteriorates, and our eyes and brain can experience a decline in function, but there are steps you can take to support your visual and cognitive health. Regular eye exams are crucial for detecting and treating vision problems early on, and making healthy choices such as eating a nutritious diet and exercising regularly can also help. However, with busy schedules, it can be difficult to find the time to devote to a healthy lifestyle. This is where the Sight Care supplement comes in. It's designed to support both vision and brain health with its blend of natural ingredients that have been shown to promote healthy vision and cognitive function You must not compromise your eye health for momentary exhilaration. If you are glued to digital screens day and night, you must take measures to prevent eye diseases like age-related macular degeneration. The SightCare vision supplement has been made using 100% natura
Nathan Goodyear

High Estrogen in Men After Injectable Testo... [Am J Mens Health. 2014] - PubMed - NCBI - 0 views

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    Again, Testosterone and here Estradiol are merely there for libido and sex.  What tunnel vision?!  What about hsCRP?  What about fibrinogen?  What about IL-1beta?  What about TNF-alpha?  These inflammatory cytokines have all been reported to elevate as a result of estrogen production in men.   And PSA?  No mention of it here.   This linear, tunnel vision thinking on hormones has got to stop! The study points out that all clients were using AIs and SERMs irregardless of whether they had elevated estrogens or not.  That is not a well designed study.  One group should have had AI's if elevated estrogens were present and another group should not--this would compare the effects of aromatase activity.  Second, this was simply a retrospective chart review.  Third, a 50% conversion of 34,000 + men is very high when you look at the literature.  Fourth, they point to gynecomastia as a means of negative?  The cardiovascular implications are more significant.  These studies just seem to focus on superficial things.  Fifth, did libido problems exist before?  What were the free levels?   This falls in the paucity of data (2 studies) that point to excessive lowering of estradiol effecting libido and sexual performance.
fnfdoc

Friends And Family Doctor | Health Blog - 0 views

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    Staying in shape can be really tough in today's world. We, at fnfdoc.com, join hands with the community to learn more about health and wellness. We talk about the ways to achieve optimum strength and fitness. Let's learn more about the nature of disease. Because you can only fight what you understand.
learnivfindia

How to get the best out of your IVF journey? - 0 views

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    Goral Gandhi, one of the most talked-about embryologists in India, talks about people's ignorance about the same issues. As per him, only 2 out of every 5 infertile couples are really aware of their medical situation.
fitspresso

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Nathan Goodyear

JISSN | Full text | International Society of Sports Nutrition position stand: creatine ... - 0 views

  • the energy supplied to rephosphorylate adenosine diphosphate (ADP) to adenosine triphosphate (ATP) during and following intense exercise is largely dependent on the amount of phosphocreatine (PCr) stored in the muscle
  • Creatine is chemically known as a non-protein nitrogen
  • It is synthesized in the liver and pancreas from the amino acids arginine, glycine, and methionine
  • ...26 more annotations...
  • Approximately 95% of the body's creatine is stored in skeletal muscle
  • About two thirds of the creatine found in skeletal muscle is stored as phosphocreatine (PCr) while the remaining amount of creatine is stored as free creatine
  • The body breaks down about 1 – 2% of the creatine pool per day (about 1–2 grams/day) into creatinine in the skeletal muscle
  • The magnitude of the increase in skeletal muscle creatine content is important because studies have reported performance changes to be correlated to this increase
  • "loading" protocol. This protocol is characterized by ingesting approximately 0.3 grams/kg/day of CM for 5 – 7 days (e.g., ≃5 grams taken four times per day) and 3–5 grams/day thereafter [18,22]. Research has shown a 10–40% increase in muscle creatine and PCr stores using this protocol
  • Additional research has reported that the loading protocol may only need to be 2–3 days in length to be beneficial, particularly if the ingestion coincides with protein and/or carbohydrate
  • A few studies have reported protocols with no loading period to be sufficient for increasing muscle creatine (3 g/d for 28 days)
  • Cycling protocols involve the consumption of "loading" doses for 3–5 days every 3 to 4 weeks
  • Most of these forms of creatine have been reported to be no better than traditional CM in terms of increasing strength or performance
  • Recent studies do suggest, however, that adding β-alanine to CM may produce greater effects than CM alone
  • These investigations indicate that the combination may have greater effects on strength, lean mass, and body fat percentage; in addition to delaying neuromuscular fatigue
  • creatine phosphate has been reported to be as effective as CM at improving LBM and strength
  • Green et al. [24] reported that adding 93 g of carbohydrate to 5 g of CM increased total muscle creatine by 60%
  • Steenge et al. [23] reported that adding 47 g of carbohydrate and 50 g of protein to CM was as effective at promoting muscle retention of creatine as adding 96 g of carbohydrate.
  • It appears that combining CM with carbohydrate or carbohydrate and protein produces optimal results
  • Studies suggest that increasing skeletal muscle creatine uptake may enhance the benefits of training
  • Nearly 70% of these studies have reported a significant improvement in exercise capacity,
  • Long-term CM supplementation appears to enhance the overall quality of training, leading to 5 to 15% greater gains in strength and performance
  • Nearly all studies indicate that "proper" CM supplementation increases body mass by about 1 to 2 kg in the first week of loading
  • short-term adaptations reported from CM supplementation include increased cycling power, total work performed on the bench press and jump squat, as well as improved sport performance in sprinting, swimming, and soccer
  • Long-term adaptations when combining CM supplementation with training include increased muscle creatine and PCr content, lean body mass, strength, sprint performance, power, rate of force development, and muscle diameter
  • subjects taking CM typically gain about twice as much body mass and/or fat free mass (i.e., an extra 2 to 4 pounds of muscle mass during 4 to 12 weeks of training) than subjects taking a placebo
  • The gains in muscle mass appear to be a result of an improved ability to perform high-intensity exercise via increased PCr availability and enhanced ATP synthesis, thereby enabling an athlete to train harder
  • there is no evidence to support the notion that normal creatine intakes (< 25 g/d) in healthy adults cause renal dysfunction
  • no long-term side effects have been observed in athletes (up to 5 years),
  • One cohort of patients taking 1.5 – 3 grams/day of CM has been monitored since 1981 with no significant side effects
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    Nice review of the data, up to the publication date, on creatine.
fnfdoc

Why You Should Go Gluten Free | Your Health Our Priority - 0 views

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    What is all this hype about a gluten free diet? Why do some people lose their weight after switching to a gluten free diet? What are the health benefits of avoiding grains? Read on to find out what doctors and nutritionists have to say about a gluten free diet plan.
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    You must have heard of a gluten free diet on the TV or from a friend. There is a lot of hype in the press about gluten free diets for people who have been diagnosed with Celiac's disease. At the same time, there are those who wish to go gluten free because of the health benefits involved.
Nathan Goodyear

Access : Neuroimmunology: Estrogen receptor ligands suppress inflammatory responses in ... - 0 views

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    Granted, this study was in an animal model of MS, but signaling through ER-beta was shown to decrease inflammation from astrocytes and microglial cells in the brain.  These immune cells are known to play prominent roles in excitotoxic diseases such as MS.  So, again, it is not just about the message, but also about how the message is interpreted.
Nathan Goodyear

PLOS Medicine: Leisure Time Physical Activity of Moderate to Vigorous Intensity and Mor... - 0 views

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    no surprise that sedentary lifestyle associated with decreased lifespan. Exercise is beneficial in normal weight and obese individuals.  Also of note, one does not need to train for a marathon to see the health benefits.  Exercise is more about intensity than it is about duration/frequency.
Nathan Goodyear

Progesterone metabolites in breast cancer - 1 views

  • 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
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  • 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
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    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.
Nathan Goodyear

Evidence that disputes BCBS saliva policy statement - 0 views

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    This is a summary of just some of the evidence that disputes BCBS saliva policy. The important notes are this is just SOME (much more is available) and that these articles PREDATE the author date of the policy. With BCBS, it is not about scientific evidence, it is just they don't want to pay for saliva testing. That is ok, just be honest about it.
Nathan Goodyear

The Journal of Nutritional Biochemistry - Record - 0 views

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    study shows that smoking cessation, physical inactivity, menopause, hysterectomy and energy intake associated with the perimenopause weight gain.  What is interesting about it is the energy imbalance is small that results in a big weight gain over time.  We need to look closely and be more frank with out clients about the risk that a hysterectomy poses for her health post surgery.
Dr. Jennifer Martinick

Dr Jennifer Martinick - A Review About Her - 1 - 0 views

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    Dr Jennifer Martinick is a prominent hair transplant surgeon. She runs the well established Martinick Hair Restoration clinics at four leading cities of Australia. Read on a Review about her (Part 1).
Dr. Jennifer Martinick

Dr Jennifer Martinick - Warning about Hair Disorders - 0 views

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    Dr Jennifer Martinick shares this informative slide show to spread awareness about Hair Disorders.
Nathan Goodyear

Gonadal Steroids and Body Composition, Strength, and Sexual Function in Men - NEJM - 0 views

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    This study confirms what we know about Testosterone, but this study finds that Estradiol aids libido and fat loss.  The conclusion on Estradiol I believe to be extremely premature.  First, it flies in the face of all the accumulative data on estradiol, second, what normal physiology is being replicated with goserelin???  Goserelin has been shown to decrease Prolactin which can effect libido also.  What about the potential there?  The men included in the study were described as "healthy".  So, you are taking "healthy" normal funcitoning men, throwing in a monkey wrench and looking at the effects of your monkey wrench.  Sorry, not physiologic.  In all my practice, I have seen one man with low Estradiol levels.  There is no reference to the hormone levels in the men preceding the suppression with goserelin.  This is a study that lacks application.
Nathan Goodyear

Vitamin D status and ill health: a systematic review : The Lancet Diabetes & Endocrinology - 0 views

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    Another ill conceived conclusion by the authors.  IF you are going to study something, know everything about it.  They authors make a major statement about vitamin D, yet they seem to understand a basic understanding of vitamin dosing.  The authors stated that dosing 2,000 IU of vitamin D in those with levels < 50 provided no benefit.  That is of course correct, because 2,000 IU daily won't hold any levels stable, let alone increase levels to 70-80 where they need to be.  The authors of this study are stuck in the traditional RDC thinking here. What is interesting is that low vitamin D was associated with CVD, MS, dyslipidemia, inflammation, glucose dysmetabolism, infections, mood disorders, decline in cognition, impaired physical functioning, and all-cause mortality,  But, vitamin D supplementation is only good for bones.  The authors of this study make a mockery of medicine.
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