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Nathan Goodyear

Histamine and histamine intolerance - 0 views

  • Histamine intolerance can develop through both increased availability of histamine and impaired histamine degradation
  • increased availability may be an endogenous histamine overproduction caused by allergies, mastocytosis, bacterias, gastrointestinal bleeding, or increased exogenous ingestion of histidine or histamine by food or alcohol
  • Other biogenic amines, such as putrescine, may also be involved in displacing histamine from its mucosal mucine linkage, which results in an increase of free absorbable histamine in circulation
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  • the main cause of histamine intolerance is an impaired enzymatic histamine degradation caused by genetic or acquired impairment of the enzymatic function of DAO or HNMT
  • The main enzyme for metabolism of ingested histamine is diamine oxidase (DAO)
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    good discussion of histamine and histamine intolerance.  All centers around diamine oxidase function (DAO).
Nathan Goodyear

Histamine and histamine intolerance - 0 views

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    Histamine intolerance?  Can the massive increase in allergies and thus histamine release be creating problems with metabolism of histamine?  Or can some people struggle with inborn deficits of diamine oxidase?  
Nathan Goodyear

Histamine dihydrochloride and low-dose interleukin-2 as post-consolidation im... - 0 views

  • IL-2 is a central T cell-derived cytokine, which induces NK cell and T cell proliferation, differentiation and activation, and also stim-ulates the production of secondary immunostimulatory cytokines
  • combination of histamine and IL-2 thus triggers efficient NK cell-mediated killing of several types of leukemic cells, including freshly recovered human AML blasts
  • histamine improves the effects of IL-2 on T cell activation
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  • principal action of histamine is to protect cytotoxic lymphocytes from myeloid-cell-induced inactivation, thus improving the efficiency of the T and NK cell stimulation achieved by IL-2
  • random-ized Phase II study of patients with renal cell carcinoma further support the suggestion that the combination of HDC and IL-2 improves lymphocyte functions
  • HDC improves the effectiveness of IL-2-induced T and NK cell activation in cancer patients, as predicted in preclinical models
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    histamine dihydrochloride enhances immune effects of NK cells in IL02 therapy; specifically in this analysis in AML, the histamin prevented inactivation of the IL-2 activated NK cells.
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

Histamine: A Novel Approach to Cancer Immunotherapy: Cancer Investigation: Vol 18, No 4 - 0 views

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    histamin augments NK activation with IL-2 therapy. Histamine blocks the monocyte/macrophate inhibition of IL-2 induced NK activity.
Nathan Goodyear

Histamine and Interleukin-2 in Acute Myelogenous Leukemia: Leukemia & Lymphoma: Vol 27,... - 0 views

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    IL-2 + histamine to prolong remission time in AML.
Nathan Goodyear

Adjuvant histamine in cancer immunotherapy, Seminars in Cancer Biology | 10.1006/scbi.2... - 0 views

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    histamine dihydrochloride augments IL-2 stimulation of NK and blocks the monocyte/macrophage inhibition of IL-2 stimulation of NK cells.
Nathan Goodyear

Improved leukemia-free survival after postconsolidation immunotherapy with histamine di... - 0 views

  • several independent lines of evidence suggest that cytotoxic effector cells such as T cells and natural killer (NK) cells participate in protecting patients with AML against relapse
  • A plethora of mechanisms have been proposed to account for the dysfunctional antileukemic lymphocytes in AML, including the production of T-cell- and NK-cell-inhibitory factors by AML blasts,48 a deficient expression of NK-cell receptors on leukemic cells,49 inhibition of antileukemic lymphocytes by mononuclear phagocytes,4 and an impaired stimulatory interaction between the CD28 antigen expressed by T cells and contact antigens on AML blasts
  • This trial met the primary endpoint and thus showed a significantly improved LFS for patients receiving HDC/IL-2 as compared with the current standard of care
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  • T cells and NK cells with antileukemic activity can be recovered from most patients with AML in remission not receiving a transplant,
  • The present study evaluated an approach to immunotherapy in AML in which IL-2 is supplemented with histamine dihydrochloride (HDC) to enhance the function of cytotoxic antileukemic lymphocytes
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    IL-2 plus histamine in patients with AML complete remission improves leukemia free survival.
Nathan Goodyear

Histamine and mucosal mast cells in interstitial cystitis. - PubMed - NCBI - 0 views

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    Interstitial cystitis is a histamine/mast cell mediated event.
Nathan Goodyear

Histidine suppresses food intake through its conversion into neuronal histamine. - PubM... - 0 views

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    neuronal histidine to histamine conversion suppresses appetite via leptin feedback signaling.  
Nathan Goodyear

Gut Microbe-Mediated Suppression of Inflammation-Associated Colon Carcinogenesis by Lum... - 0 views

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    Only abstract available here: Gut bacteria, lactobacillus reuteri, could be the key to colon cancer prevention through inflammation control.  What is fascinating is how the gut bacteria influenced epigenetic expression of histidine decarboxylase to increase histamine production.
Nathan Goodyear

http://circ.ahajournals.org/content/circulationaha/107/18/2348.full.pdf - 0 views

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    histamine increased eNOS gene expression and thus NO production.
Nathan Goodyear

JAMA Network | JAMA | Proton Pump Inhibitor and Histamine 2 Receptor Antagonist Use and... - 0 views

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    PPI therapies and Histamine Rc blockers associated with increased vitamin B12 deficiency.
Nathan Goodyear

PLOS ONE: Mast Cell-Derived Histamine Mediates Cystitis Pain - 0 views

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    Mast cells contribute/cause the pro inflammatory response that results in pain in people with interstitial cystitis.  This is mediated via Histamine type I and type II receptors.
Nathan Goodyear

Mast cell involvement in interstitial cystitis: a review of human and experimental evid... - 0 views

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    Interstitial Cystitis is a histamine mediated inflammatory process.
Nathan Goodyear

Depression, antidepressant medications, and risk of Clostridium difficileinfection | BM... - 0 views

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    PPI therapies, histamine (specifically type II) antagonists and antidepressants are associated with clostridium difficile infection. 
Nathan Goodyear

The mast cell in interstitial cystitis: role in pathophysiology and pathogenesis. - Pub... - 0 views

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    Only abstract available here.  IC is driven by histamine from mast cells.
olivehealthcare

Hay Fever Symptoms | Hay Fever Injection | Hay Fever Treatment - 0 views

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    Between 10-15% of us suffer from hay fever symptoms. For many people it causes significant fatigue and problems with concentration and alertness. Of those 10-15% of people with hay-fever, about 10% do not respond to conventional, easily available treatments like anti-histamine tablets, nasal sprays and eye drops.
Nathan Goodyear

Dexamethasone prevents postoperative nausea and vomiting: Benefit versus risk - Science... - 0 views

  • 2.5–10 mg
  • Dexamethasone is a synthetic form of adrenocorticoid, and acts mainly as a glucocorticoid receptor with almost no mineralocorticoid receptor functions
  • dexamethasone increases synthesis of endorphin in the body,14 uplifting moods and appetite
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  • serotonin Type 3 receptor antagonist (ondansetron, dolasetron, and granisetron), dopamine Type 2 receptor antagonist (droperidol and metoclopramide), muscarinic cholinergic Type 1 receptor antagonist (scopolamine), and histamine Type 1 receptor antagonist (promethazine and prochlorperazine)
  • dexamethasone can effectively prevent PONV7, 8, 9 induced by epidural morphine used to reduce postoperative pain
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    Dexamethasone for nausea
Nathan Goodyear

Opioid-induced nausea and vomiting - Smith - Annals of Palliative Medicine - 0 views

  • Some of the “emetogenic” receptors that have been proposed are dopamine-2 (D2), histamine-1 (H1), DOR, 5-hydroxytryptamine (serotonin) (5-HT3), acetylcholine (ACh), neurokinin-1 (NK-1), and cannabinoid receptor-1 (CB1)
  • Olanzapine decreased morphine-induced nausea and vomiting in a dose-dependent manner.
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    Good review of meds for nausea.
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