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Nathan Goodyear

Unveiling the Mechanisms for Decreased Glutathione in Individuals with HIV Infection - 0 views

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    men with HIV have GSH depleted macrophages.  GSH is the reduced, ready to act form of Glutathione.  In contrast, the macrophages were high in the oxidized form of Glutathione--GSSG.  In HIV, the high inflammation increased oxidative stress, likely overwhelmed Nrf2 activation and resulted in decreased GSH synthase transcription and thus decreased Glutathione production balance.
Nathan Goodyear

Does increased aromatase activity in adipose fibroblasts cause low sexual desire in pat... - 0 views

  • high oestrogen levels in men do not necessarily result in a fall in androgen levels
  • These high oestrogen levels, therefore, seem capable of decreasing sexual libido and lowering sexual activity
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    Increased aromatase activity and resultant estrogen production negatively effects libido in HIV men.  I don't believe that this effect is just found in those with HIV, but can be extrapolated to all.
Nathan Goodyear

Morning free and total testosterone in HIV-infected men: implications for the assessmen... - 0 views

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    low T is found in 20-70% of men with HIV.  What is interesting about this article is that Total Testosterone was found to be a poor assessment of biological active Testosterone.  Free Testosterone assessed in the am was shown to be a better functional assessment in these men.  Serum is a poor choice though.  The process of equilibrium dialysis to calculate free Testosterone is filled with variables that will effect reliability.  Increases SHBG was found associated.
Nathan Goodyear

Effect of Increasing Glutathione With Cysteine and Glycine Supplementation on Mitochond... - 0 views

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    Supporting glutathione levels with the precursors cysteine and glycine improved insulin receptor function, body fat, and muscle strength in HIV individuals.
Nathan Goodyear

Glutathione supplementation improves macrophage functions in HIV. - PubMed - NCBI - 0 views

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    reduced glutathione, via increased oxidative stress, levels lost in HIV.  NAC and liposomal Glutathione increased innate immune function--macrophages.
Nathan Goodyear

HUMAN VIRAL ONCOGENESIS: A CANCER HALLMARKS ANALYSIS - 0 views

  • pproximately twelve percent of all human cancers are caused by oncoviruses
  • hepatitis B virus, (HBV) hepatitis C virus (HCV), Epstein Barr Virus (EBV), high-risk Human Papillomaviruses (HPVs), Human T lymphotropic Virus-1 (HTLV-1), HIV and Kaposi’s sarcoma herpesvirus (KSHV)
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    good review of the oncoviruses: EBV, HBV, HCV, HPV, HTLV-1, HIV, and KSHV.  UP to 12% of cancers are caused by oncoviruses
Nathan Goodyear

Counteracting muscle wasting in HIV-infected individuals - 0 views

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    HIV/AIDS patients are plagues with muscle loss through varying mechanism. This article discusses the various contributors to the muscle mass found in these men. However, this can be applicable to other men with chronic muscle loss, low T, HGH deficiency...
Nathan Goodyear

Does increased aromatase activity in adipose fibroblasts cause low sexual desire in pat... - 0 views

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    increased testosterone to estrogen conversion, in part, stimulated by inflammatory cytokines: TNF, and IL-6.  They propose aromatase inhibition to decrease testosterone to estrogen conversion.  This study looked at individuals with HIV.
Nathan Goodyear

Effect of increasing glutathione with cysteine and glycine supplementation on mitochond... - 0 views

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    Abstract only available due to pre-release.  Cysteine and glycine supplementation feed the glutathione pathways.  In HIV men, this improved insulin sensitivity, body composition, and muscle strength.
Nathan Goodyear

PLOS ONE: Candida dubliniensis: An Appraisal of Its Clinical Significance as a Bloodstr... - 0 views

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    It is hard to differentiate between Candida albicans and candida dubliniensis.  Candida dubliniensis was first found in HIV positive individuals.
Nathan Goodyear

Low testosterone is associated with poor health status in men with ... - PubMed - NCBI - 0 views

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    Lower Testosterone levels are found in men with more advanced HIV.  This relationship is bidirectional.  This decreased biomarker is likely more a biomarker of poor health than one of a direct relationship.  As in the fT3 is lower in hypogonadal men versus eugonadal men.  This points to the significant problems in the way Testosterone is thought of and used in therapy for men today.  For many men, low T is the effect and not the cause.
Nathan Goodyear

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC54720/ - 0 views

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    Vitamin C found to inhibit HIV replication/production. This require 4 days of exposure to cause effect as 1 day did not provide effect.
Nathan Goodyear

The telomerase activator TA-65 elongates short telomeres and increases health span of a... - 0 views

  • studies have demonstrated that the shortest telomeres are causal of reduced cell viability
  • a stable and enforced expression of telomerase leads to an improved health-span, accompanied by an extension of lifespan
  • TA-65 influences the percentage of cellular short telomeres through the activation of telomerase
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  • TA-65 administration during 4 months significantly improved the capacity to uptake glucose after a glucose pulse
  • liver protective action of TA-65
  • A disadvantage of mTERT potentiation could be associated to its capacity to favor proliferation of cancerous cells in murine models
  • TA-65 treated mice presented a similar incidence of malignant cancers at time of death, with a tendency to show decreased sarcomas and slightly increased lymphomas
  • We demonstrate here that TA-65 leads to a significant rescue of short telomeres through telomerase activation
  • TA-65 treatment increases proliferation and mobilization potential of mouse keratinocytes in vitro, a situation mimicking telomerase overexpression
  • TAT2, a similar molecule, have beneficial effects in the activation of CD8+ T lymphocytes from HIV-infected patients where they observe an increase of the proliferative potential and enhancement of cytokine/chemokine production
  • TA-65 resulted in a similar rescue of short telomeres in leukocytes post-treatment as observed with humans, most likely through an activation of telomerase
  • we observe that TA-65 lead to 10 fold increase of telomerase RNA levels in the liver of treated mice comparing to the non-treated same-age cohorts
  • TA-65 regulates telomerase at the transcription level, probably through the regulation of the MAPK pathway
  • TA-65 dependent telomerase activation results in a better organ fitness as demonstrated by the improved scores at the glucose tolerance test and insulin levels at fasting
  • TA-65 supplemented mice also present modest enhancement of the subcutaneous and epidermal thickness, as well as higher bone density, representative of an overall fitness status improvemen
  • TA-65 treated mice present higher levels of RBC and hemoglobin comparing to the control cohorts
  • improved health-span of TA-65 treated mice is not accompanied by increased cancer incidence, which may be related to the fact that TERT levels are very modestly increased in all tissues tested except for the liver
  • systemic telomerase overexpression from the germline leads to protection from aging associated pathologies
  • similar situation could be mimicked expressing telomerase late in life in a telomerase deficient background
  • we observed a higher proliferation rate and a partial protection from cell death in some tissues of TA65 treated mice
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    TA-65 shown to increase telomerase activity, and thus telomere length of short telomeres, in mouse study.  
Jackson Samuel

Small breakthroughs offer big hope of AIDS 'cure' - 0 views

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    Small but significant breakthrough studies on people who have been able to overcome or control HIV were presented at a major world conference on ways to stem the three-decade-old disease. One study focused on a group of 12 patients in France who began treatment on antiretroviral drugs within 10 weeks of becoming infected with human immunodeficiency virus, but then stopped the therapy after nearly three years.
Nathan Goodyear

Impact of vitamin B6 status on psychological distress in a longitudinal study of HIV-1 ... - 0 views

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    Vitamin B6 very important in brain physiologic function
Nathan Goodyear

Testosterone Deficiency, Cardiac Health, and Older Men - 0 views

  • 2.1 standard deviations in total testosterone was associated with a 25% increase in mortality
  • Erectile dysfunction is an established marker for future cardiovascular risk and the major presenting symptom leading to a diagnosis of low testosterone
  • There is a considerable body of evidence that low testosterone is associated with increased cardiovascular and cancer mortality
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  • There is considerable evidence of modest cardiac and metabolic benefits that are shown to reduce cardiovascular risk plus sexual, mood, and quality of life changes associated with restoring testosterone levels
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    low Testosterone is associated with increased mortality in men and Testosterone therapy in men with low T is associated with a reduction in mortality in men.
Nathan Goodyear

Demystified . . . Human endogenous retroviruses - 0 views

  • HERVs have been inherited by successive generations and it is possible that some have conferred biological benefits
  • However, several HERVs have been implicated in certain cancers and autoimmune diseases
  • HERVs constitute about 1% of the human genome
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  • Human endogenous retroviruses (HERVs) represent footprints of previous retroviral infection and have been termed “fossil viruses”
  • HERVs possess a similar genomic organisation to present day exogenous retroviruses such as human immunodeficiency virus (HIV) and human T cell leukaemia virus (HTLV)
  • Retroviruses in effect are retrograde, because the flow of genetic information is reversed compared with the normal pathway of molecular biosynthesis—DNA → RNA → protein. Indeed, all retroviruses necessitate the conversion of viral RNA into a cDNA intermediary, which is catalysed by the enzyme reverse transcriptase
  • Overall, human endogenous retroviruses constitute about 1% of the human genome”
  • some HERVs have been implicated in certain autoimmune diseases and cancers
  • A unit of sugar, phosphate, and base is strictly termed a nucleotide
  • human genes are composed of exons, which are transcribed and translated into amino acids
  • introns, which are interspersed between exons and represent non-translated regions that contribute to the large size of some genes
  • convincing argument for the possible involvement of HERVs in malignancy
  • HERVs may be involved in carcinogenesis by virtue of the expression of HERV mRNA,26 functional proteins,27 or retroviral-like particles
  • They may also be associated with the generation of new promoters29 or the activation of proto-oncogenes
  • inhibition of an effective immune response,
  • encode immunosuppressive proteins
  • “It has been suggested that HERV-K may be important in the progression of testicular germ cell tumours through inhibition of an effective immune response”
  • HERV-K might be important in the pathogenesis of human breast cancer
  • activation of proto-oncogenes of the ras family is common in many tumour types, and some studies have suggested a potential role for HERVs in ras activation
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    good review of HERVs.
Nathan Goodyear

How is the Immune System Suppressed by Cancer - 1 views

  • nitric oxide (NO) released by tumor cells
  • Excellent work by Prof de Groot of Essen, indicated by adding exogenous xanthine oxidase ( XO) in hepatoma cells, hydrogen peroxide was produced to destroy the hepatoma cells
  • NO from eNOS in cancer cells can travel through membranes and over long distances in the body
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  • NO also is co linked to VEGF which in turn increases the antiapoptotic gene bcl-2
  • The other important influence of NO is in its inhibition of the proapoptoic caspases cascade. This in turn protects the cells from intracellular preprogrammed death.
  • nitric oxide in immune suppression in relation to oxygen radicals is its inhibitory effect on the binding of leukocytes (PMN) at the endothelial surface
  • Inhibition of inducible Nitric Oxide Synthase (iNOS)
  • NO from the tumor cells actually suppresses the iNOS, and in addition it reduces oxygen radicals to stop the formation of peroxynitrite in these cells. But NO is not the only inhibitor of iNOS in cancer.
  • Spermine and spermidine, from the rate limiting enzyme for DNA synthases, ODC, also inhibit iNOS
  • tolerance in the immune system that decreases the immune response to antigens on the tumors
  • Freund’s adjuvant
  • increase in kinases in these cells which phosphorylate serine, and tyrosine
  • responsible for activation of many growth factors and enzymes
  • phosphorylated amino acids suppress iNOS activity
  • Hexokinase II
  • Prostaglandin E2, released from tumor cells is also an inhibitor of iNOS, as well as suppressing the immune system
  • Th-1 subset of T-cells. These cells are responsible for anti-viral and anti-cancer activities, via their cytokine production including Interleukin-2, (IL-2), and Interleukin-12 which stimulates T-killer cell replication and further activation and release of tumor fighting cytokines.
    • Nathan Goodyear
       
      Th1 cells stimulate NK and other tumor fighting macrophages via IL-2 and IL-12; In contrast, Th2, which is stimulated in allergies and parasitic infections, produce IL-4 and IL-10.  IL-4 and IL-10 inhibit TH-1 activation and the histamine released from mast cell degranulation upregulates T suppressor cells to further immune suppression.
  • Th-2 subset of lymphocytes, on the other hand are activated in allergies and parasitic infections to release Interleukin-4 and Interleukin-10
  • These have respectively inhibitory effects on iNOS and lymphocyte Th-1 activation
  • Mast cells contain histamine which when released increases the T suppressor cells, to lower the immune system and also acts directly on many tumor Histamine receptors to stimulate tumor growth
  • Tumor cells release IL-10, and this is thought to be one of the important areas of Th-1 suppression in cancer patients
  • IL-10 is also increased in cancer causing viral diseases such as HIV, HBV, HCV, and EBV
  • IL-10 is also a central regulator of cyclooxygenase-2 expression and prostaglandin production in tumor cells stimulating their angiogenesis and NO production
  • nitric oxide in tumor cells even prevents the activation of caspases responsible for apoptosis
    • Nathan Goodyear
       
      NO produced by cancer cells inhibits proapoptotic pathways such as the caspases.
  • early stages of carcinogenesis, which we call tumor promotion, one needs a strong immune system, and fewer oxygen radicals to prevent mutations but still enough to destroy the tumor cells should they develop
  • later stages of cancer development, the oxygen radicals are decreased around the tumors and in the tumor cells themselves, and the entire cancer fighting Th-1 cell replication and movement are suppressed. The results are a decrease in direct toxicity and apoptosis, which is prevented by NO, a suppression of the macrophage and leukocyte toxicity and finally, a suppression of the T-cell induced tumor toxicity
  • cGMP is increased by NO
  • NO in cancer is its ability to increase platelet-tumor cell aggregates, which enhances metastases
  • the greater the malignancies and the greater the metastatic potential of these tumors
  • The greater the NO production in many types of tumors,
  • gynecological
  • elevated lactic acid which neutralizes the toxicity and activity of Lymphocyte immune response and mobility
  • The lactic acid is also feeding fungi around tumors and that leads to elevated histamine which increases T-suppressor cells.  Histamine alone stimulates many tumor cells.
    • Nathan Goodyear
       
      The warburg effect in cancer cells results in the increase in local lactic acid production which suppresses lymphocyte activity and toxicity as well as stimulates histamine production with further stimulates tumor cell growth.
  • T-regulatory cells (formerly,T suppressor cells) down regulate the activity of Natural killer cells
  • last but not least, the Lactic acid from tumor cells and acidic diets shifts the lymphocyte activity to reduce its efficacy against cancer cells and pathogens in addition to altering the bacteria of the intestinal tract.
  • intestinal tract bacteria in cancer cells release sterols that suppress the immune system and down regulate anticancer activity from lymphocytes.
  • In addition to the lactic acid, adenosine is also released from tumors. Through IL-10, adenosine and other molecules secreted by regulatory T cells, the CD8+ cells can be inactivated to an anergic state
  • Adenosine up regulates the PD1 receptor in T-1 Lymphocytes and inhibits their activity
  • Adenosine is a purine nucleoside found within the interstitial fluid of solid tumors at concentrations that are able to inhibit cell-mediated immune responses to tumor cells
  • Adenosine appears to up-regulate the PD1 receptor in T-1 Lymphocytes and inhibits the immune system further
  • Mast cells with their release of histamine lower the immune system and also stimulate tumor growth and activate the metalloproteinases involved in angiogenesis and metastases
  • COX 2 inhibitors or all trans-retinoic acid
  • Cimetidine, an antihistamine has been actually shown to increase in apoptosis in MDSC via a separate mechanism than the antihistamine effect
    • Nathan Goodyear
       
      cimetidine is an H2 blocker
  • interleukin-8 (IL-8), a chemokine related to invasion and angiogenesis
  • In vitro analyses revealed a striking induction of IL-8 expression in CAFs and LFs by tumor necrosis factor-alpha (TNF-alpha)
  • these data raise the possibility that the majority of CAFs in CLM originate from resident LFs. TNF-alpha-induced up-regulation of IL-8 via nuclear factor-kappaB in CAFs is an inflammatory pathway, potentially permissive for cancer invasion that may represent a novel therapeutic target
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    Great review of the immunosuppression in cancer driven by the likes of NO.
Nathan Goodyear

Sars-Cov-2 Kills T-Cells, Just Like HIV - by Igor Chudov - 0 views

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    Just an article.
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