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Nathan Goodyear

Estrogen Receptor β: Expression Profile and Possible Anti-Inflammatory Role i... - 0 views

jpet.aspetjournals.org/...83.long

estrogen receptor ER-beta ER beta anti-inflammation anti-inflammatory disease

shared by Nathan Goodyear on 23 Nov 12 - No Cached
  • Nathan Goodyear on 23 Nov 12
     
    Estrogen receptor beta and it's anti-inflammatory role in disease.
Nathan Goodyear

JAMA Network | JAMA | Antidepressant Drug Effects and Depression Severity:  A... - 0 views

jama.jamanetwork.com/article.aspx

depression anti-depressants

shared by Nathan Goodyear on 11 Nov 13 - No Cached
  • Nathan Goodyear on 11 Nov 13
     
    The benefits of anti-depressants in mild to moderate depression is no better than placebo.  However, in severe depression and with increasing severity, anti-depressants are better than placebo.
wheelchairindia9

Recliner Wheelchair - 0 views

www.wheelchairindia.com/...RECLINING-WHEELCHAIR

Prepare Complete Flexibility With Reclining Wheelchair positioned for maximum comfort available in foldable frames reclining under desks legs and feet can also be re-positioned extended head supports and seat using high quality material

shared by wheelchairindia9 on 20 May 15 - No Cached
  • wheelchairindia9 on 20 May 15
     
    Reclining wheelchairs, since the product class is built around one key feature: the capability to adjust the backrest and/or footrest into a reclined position. This feature is especially important to users who find it difficult or impossible to sit in a fully upright position, and users who sleep in their chairs frequently. For those that are looking for a more portable chair. When compared with a similar, non-reclining chair, a reclining wheelchair tends to weigh more and - unlike other manual models - manual wheelchairs that recline typically aren't foldable. reclining wheelchair compensates mechanically for body positioning by automatically readjusting armrests and lateral supports.

    Recliner wheelchair is low profile allowing to comfortably fit under tables and desks. Enjoy numerous activities with increased comfort such as stretching, napping and watching television. The ability to recline also improves circulation and the ability for sore spots to heal.

    Karma Reclining Wheelchair KM 5000:
    The karma reclining wheelchair km-5000 Transport Wheelchair is an ultra lightweight folding aluminum reclining wheelchair. With full length padded armrests, an adjustable height head pillow, and more this wheelchair has added comfort for any user. This chair also features swing-away elevating footrests and adjustable length leg supports and footplates. With a weight of 33 Lbs this chair can be transported with ease.

    Karma Reclining Wheelchair KM 5000 Features:
    Folding 6061 T-6 Aircraft-grade aluminum frame in black
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    Backrest Reclines 90°~163° and includes anti-tippers
    Full length padded detachable armrests with side panels
    Swing-away detachable elevating footrests
    Adjustable length leg supports & footplates
    Adjustable-height head pillow
    14" Mag wheels with flat free polyurethane tires
    7" x 1" Flat free front polyurethane casters
    Adjustab
Nathan Goodyear

Antidepressants inhibit interferon-gamma-induced ... [Exp Neurol. 2007] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...17481608

anti-depressants inflammation IL-6 depression

shared by Nathan Goodyear on 14 Sep 11 - No Cached
  • Nathan Goodyear on 14 Sep 11
     
    anti-depressants inhibit inflammatory IL-6 production from microglial cells in brain, suggesting anti-inflammatory effects of antidepressants as role in improving depression symptoms
Meredith Blige

Proven Very Effective Anti-Snoring Products - 1 views

My husband kept asking me the question "how can I stop snoring" because I always told him that I cannot get enough sleep due to his loud snoring. He was worried that I might get sick, so we searche...

how can I stop snoring

started by Meredith Blige on 25 Oct 11 no follow-up yet
Nathan Goodyear

Cancer cells metabolically "fertilize" the tumor microenvironment with hydrogen peroxid... - 0 views

www.ncbi.nlm.nih.gov/...PMC3180189

cancer reverse warburg effect warburg effect NF-kapppB HIF-1alpha Cav-1 H2O2

shared by Nathan Goodyear on 12 Nov 14 - No Cached
  • reducing oxidative stress with powerful antioxidants, is an important strategy for cancer prevention, as it would suppress one of the key early initiating steps where DNA damage and tumor-stroma metabolic-coupling begins. This would prevent cancer cells from acting as metabolic “parasites
  • Oxidative stress in cancer-associated fibroblasts triggers autophagy and mitophagy, resulting in compartmentalized cellular catabolism, loss of mitochondrial function, and the onset of aerobic glycolysis, in the tumor stroma. As such, cancer-associated fibroblasts produce high-energy nutrients (such as lactate and ketones) that fuel mitochondrial biogenesis and oxidative metabolism in cancer cells. We have termed this new energy-transfer mechanism the “reverse Warburg effect.
  • Then, oxidative stress, in cancer-associated fibroblasts, triggers the activation of two main transcription factors, NFκB and HIF-1α, leading to the onset of inflammation, autophagy, mitophagy and aerobic glycolysis in the tumor microenvironment
  • ...38 more annotations...
  • oxidative stress and ROS, produced in cancer-associated fibroblasts, has a “bystander effect” on adjacent cancer cells, leading to DNA damage, genomic instability and aneuploidy, which appears to be driving tumor-stroma co-evolution
  • tumor cells produce and secrete hydrogen peroxide, thereby “fertilizing” the tumor microenvironment and driving the “reverse Warburg effect.”
  • This type of stromal metabolism then produces high-energy nutrients (lactate, ketones and glutamine), as well as recycled chemical building blocks (nucleotides, amino acids, fatty acids), to literally “feed” cancer cells
  • loss of stromal caveolin (Cav-1) is sufficient to drive mitochondrial dysfunction with increased glucose uptake in fibroblasts, mimicking the glycolytic phenotype of cancer-associated fibroblasts.
  • oxidative stress initiated in tumor cells is transferred to cancer-associated fibroblasts.
  • Then, cancer-associated fibroblasts show quantitative reductions in mitochondrial activity and compensatory increases in glucose uptake, as well as high ROS production
  • These findings may explain the prognostic value of a loss of stromal Cav-1 as a marker of a “lethal” tumor microenvironment
  • Interruption of this process, by addition of catalase (an enzyme that detoxifies hydrogen peroxide) to the tissue culture media, blocks ROS activity in cancer cells and leads to apoptotic cell death in cancer cells
  • our results may also explain the “field effect” in cancer biology,5 as hydrogen peroxide secreted by cancer cells, and the propagation of ROS production, from cancer cells to fibroblasts, would create an increasing “mutagenic field” of ROS production, due to the resulting DNA damage
  • aerobic glycolysis takes place in cancer-associated fibroblasts, rather than in tumor cells, as previously suspected.
  • In this new paradigm, cancer cells induce oxidative stress in neighboring cancer-associated fibroblasts
  • cancer-associated fibroblasts have the largest increases in glucose uptake
  • cancer cells secrete hydrogen peroxide, which induces ROS production in cancer-associated fibroblasts
  • Then, oxidative stress in cancer-associated fibroblast leads to decreases in functional mitochondrial activity, and a corresponding increase in glucose uptake, to fuel aerobic glycolysis
  • cancer cells show significant increases in mitochondrial activity, and decreases in glucose uptake
  • fibroblasts and cancer cells in co-culture become metabolically coupled, resulting in the development of a “symbiotic” or “parasitic” relationship.
  • cancer-associated fibroblasts undergo aerobic glycolysis (producing lactate), while cancer cells use oxidative mitochondrial metabolism.
  • We have previously shown that oxidative stress in cancer-associated fibroblasts drives a loss of stromal Cav-1, due to its destruction via autophagy/lysosomal degradation
  • a loss of stromal Cav-1 is sufficient to induce further oxidative stress, DNA damage and autophagy, essentially mimicking pseudo-hypoxia and driving mitochondrial dysfunction
  • loss of stromal Cav-1 is a powerful biomarker for identifying breast cancer patients with early tumor recurrence, lymph-node metastasis, drug-resistance and poor clinical outcome
  • this type of metabolism (aerobic glycolysis and autophagy in the tumor stroma) is characteristic of a lethal tumor micro-environment, as it fuels anabolic growth in cancer cells, via the production of high-energy nutrients (such as lactate, ketones and glutamine) and other chemical building blocks
  • the upstream tumor-initiating event appears to be the secretion of hydrogen peroxide
  • one such enzymatically-active protein anti-oxidant that may be of therapeutic use is catalase, as it detoxifies hydrogen peroxide to water
  • numerous studies show that “catalase therapy” in pre-clinical animal models is indeed sufficient to almost completely block tumor recurrence and metastasis
  • by eliminating oxidative stress in cancer cells and the tumor microenvironment,55 we may be able to effectively cut off the tumor's fuel supply, by blocking stromal autophagy and aerobic glycolysis
  • breast cancer patients show systemic evidence of increased oxidative stress and a decreased anti-oxidant defense, which increases with aging and tumor progression.68–70 Chemotherapy and radiation therapy then promote further oxidative stress.69 Unfortunately, “sub-lethal” doses of oxidative stress during cancer therapy may contribute to tumor recurrence and metastasis, via the activation of myofibroblasts.
  • a loss of stromal Cav-1 is associated with the increased expression of gene profiles associated with normal aging, oxidative stress, DNA damage, HIF1/hypoxia, NFκB/inflammation, glycolysis and mitochondrial dysfunction
  • cancer-associated fibroblasts show the largest increases in glucose uptake, while cancer cells show corresponding decreases in glucose uptake, under identical co-culture conditions
  • Thus, increased PET glucose avidity may actually be a surrogate marker for a loss of stromal Cav-1 in human tumors, allowing the rapid detection of a lethal tumor microenvironment.
  • it appears that astrocytes are actually the cell type responsible for the glucose avidity.
  • In the brain, astrocytes are glycolytic and undergo aerobic glycolysis. Thus, astrocytes take up and metabolically process glucose to lactate.7
  • Then, lactate is secreted via a mono-carboxylate transporter, namely MCT4. As a consequence, neurons use lactate as their preferred energy substrate
  • both astrocytes and cancer-associated fibroblasts express MCT4 (which extrudes lactate) and MCT4 is upregulated by oxidative stress in stromal fibroblasts.34
  • In accordance with the idea that cancer-associated fibroblasts take up the bulk of glucose, PET glucose avidity is also now routinely used to measure the extent of fibrosis in a number of human diseases, including interstitial pulmonary fibrosis, postsurgical scars, keloids, arthritis and a variety of collagen-vascular diseases.
  • PET glucose avidity and elevated serum inflammatory markers both correlate with poor prognosis in breast cancers.
  • PET signal over-estimates the actual anatomical size of the tumor, consistent with the idea that PET glucose avidity is really measuring fibrosis and inflammation in the tumor microenvironment.
  • human breast and lung cancer patients can be positively identified by examining their exhaled breath for the presence of hydrogen peroxide.
  • tumor cell production of hydrogen peroxide drives NFκB-activation in adjacent normal cells in culture6 and during metastasis,103 directly implicating the use of antioxidants, NFκB-inhibitors and anti-inflammatory agents, in the treatment of aggressive human cancers.
  • Nathan Goodyear on 12 Nov 14
     
    Good description of the communication between cancer cells and fibroblasts.  This theory is termed the "reverse Warburg effect".
Nathan Goodyear

The river blindness drug Ivermectin and related macrocyclic lactones inhibit WNT-TCF pa... - 0 views

www.ncbi.nlm.nih.gov/...PMC4287931

ivermectin cancer WTF Selamectin

shared by Nathan Goodyear on 19 Mar 18 - No Cached
  • WNT signaling
  • early colon cancers commonly display loss of function of the tumor suppressor Adenomatous polyposis coli (APC), a key component of the β-CATENIN destruction complex
  • Other cancers also show an active canonical WNT pathway; these include carcinomas of the lung, stomach, cervix, endometrium, and lung as well as melanomas and gliomas
  • ...31 more annotations...
  • In normal embryogenesis and homeostasis, the canonical WNT pathway is activated by secreted WNT ligands produced in highly controlled context-dependent manners and in precise amounts. WNT activity is transduced in the cytoplasm, inactivates the APC destruction complex, and results in the translocation of activate β-CATENIN to the nucleus, where it cooperates with DNA-binding TCF/LEF factors to regulate WNT-TCF targets and the ensuing genomic response
  • beyond the loss of activity of the APC destruction complex, for instance throughAPC mutation, phosphorylation of β-CATENIN at C-terminal sites is required for the full activation of WNT-TCF signaling and the ensuing WNT-TCF responses in cancer.
  • The WNT-TCF response blockade that we describe for low doses of Ivermectin suggests an action independent to the deregulation of chloride channels
  • involve the repression of the levels of C-terminally phosphorylated β-CATENIN forms and of CYCLIN D1, a critical target that is an oncogene and positive cell cycle regulator.
  • the Avermectin single-molecule derivative Selamectin, a drug widely used in veterinarian medicine (Nolan & Lok, 2012), is ten times more potent acting in the nanomolar range
  • Ivermectin also diminished the protein levels of CYCLIN D1, a direct TCF target and oncogene, in both HT29 and H358 tumor cells
  • Activated Caspase3 was used as a marker of apoptosis by immunohistochemistry 48 h after drug treatment. Selamectin and Ivermectin induced up to a sevenfold increase in the number of activated Caspase3+ cells in two primary (CC14 and CC36) and two cell line (DLD1 and Ls174T) colon cancer cell types (Fig​(Fig2C).2C). All changes were significative
  • The strong downregulation of the expression of the intestinal stem cell genesASCL2 andLGR5 (van der Flieret al, 2009; Scheperset al, 2012; Zhuet al, 2012b) by Ivermectin and Selamectin (Fig​(Fig2D)2D) raised the possibility that these drugs could affect WNT-TCF-dependent colon cancer stem cell behavior
  • Pre-established H358 tumors responded to Ivermectin showing a ˜ 50% repression of growth
  • Ivermectin hasin vivo efficacy against human colon cancer xenografts sensitive to TCF inhibition with no discernable side effects
  • Ivermectin (Campbellet al, 1983), an off-patent drug approved for human use, and related macrocyclic lactones, have WNT-TCF pathway response blocking and anti-cancer activities
  • these drugs block WNT-TCF pathway responses, likely acting at the level of β-CATENIN/TCF function, affecting β-CATENIN phosphorylation status.
  • anti-WNT-TCF activities of Ivermectin and Selamectin
  • Ivermectin has a well-known anti-parasitic activity mediated via the deregulation of chloride channels, leading to paralysis and death (Hibbs & Gouaux, 2011; Lynagh & Lynch, 2012). The same mode of action has been suggested to underlie the toxicity of Ivermectin for liquid tumor cells and the potentiation or sensitization effect of Avermectin B1 on classical chemotherapeutics
  • the specificity of the blockade of WNT-TCF responses we document, at low micromolar doses for Ivermectin and low nanomolar doses for Selamectin, indicate that the blockade of WNT-TCF responses and chloride channel deregulation are distinct modes of action
  • What is key then is to find a dose and a context where the use of Ivermectin has beneficial effects in patients, paralleling our results with xenografts in mice.
  • Cell toxicity appears at doses greater (> 10 μM for 12 h or longer or > 5 μM for 48 h or longer for Ivermectin) than those required to block TCF responses and induce apoptosis.
  • Our data point to a repression of WNT-β-CATENIN/TCF transcriptional responses by Ivermectin, Selamectin and related macrocylic lactones.
  • (i) The ability of Avermectin B1 to inhibit the activation of WNT-TCF reporter activity by N-terminal mutant (APC-insensitive) β-CATENIN as detected in our screen
  • (ii) The ability of Avermectin B1, Ivermectin, Doramectin, Moxidectin and Selamectin to parallel the modulation of WNT-TCF targets by dnTCF
  • (iii) The finding that the specific WNT-TCF response blockade by low doses of Ivermectin and Selamectin is reversed by constitutively active TCF
  • (iv) The repression of key C-terminal phospho-isoforms of β-CATENIN resulting in the repression of the TCF target and positive cell cycle regulator CYCLIN D1 by Ivermectin and Selamectin
  • (v) The specific inhibition ofin-vivo-TCF-dependent, but notin-vivo-TCF-independent cancer cells by Ivermectin in xenografts.
  • These results together with the reduction of the expression of the colon cancer stem cell markersASCL2 andLGR5 (e.g., Hirschet al, 2013; Ziskinet al, 2013) raise the possibility of an inhibitory effect of Ivermectin, Selamectin and related macrocyclic lactones on TCF-dependent cancer stem cells.
  • the capacity of cancer cells to form 3D spheroids in culture, as well as the growth of these, is also WNT-TCF-dependent (Kanwaret al, 2010) and they were also affected by Ivermectin treatment
  • If Ivermectin is specific, it should only block TCF-dependent tumor growth. Indeed, the sensitivity and insensitivity of DLD1 and CC14 xenografts to Ivermectin treatment, respectively, together with the desensitization to Ivermectin actionin vivo by constitutively active TCF provide evidence of the specificity of this drug to block an activated WNT-TCF pathway in human cancer.
  • Ivermectin has a good safety profile since onlyin-vivo-dnTCF-sensitive cancer xenografts are responsive to Ivermectin treatment, and we have not detected side effects in Ivermectin-treated mice at the doses used
  • previous work has shown that side effects from systemic treatments with clinically relevant doses in humans are rare (Yang, 2012), that birth defects were not observed after exposure of pregnant mothers (Pacquéet al, 1990) and that this drug does not cross the blood–brain barrier (Kokozet al, 1999). Similarly, only dogs with mutantABCB1 (MDR1) alleles leading to a broken blood–brain barrier show Ivermectin neurotoxicity (Mealeyet al, 2001; Orzechowskiet al, 2012)
  • Indications may include treatment for incurable β-CATENIN/TCF-dependent advanced and metastatic human tumors of the lung, colon, endometrium, and other organs.
  • Ivermectin, Selamectin, or related macrocyclic lactones could also serve as topical agents for WNT-TCF-dependent skin lesions and tumors such as basal cell carcinomas
  • they might also be useful as routine prophylactic agents, for instance against nascent TCF-dependent intestinal tumors in patients with familial polyposis and against nascent sporadic colon tumors in the general aging population
  • Nathan Goodyear on 19 Mar 18
     
    Ivermectin, a common anti-parasitic, found to inhibit WTF-TCF pathway and decrease c-terminal phosophorylaiton of Beta-CATENIN all resulting in increased aptosis and inhibition of cancer growth in colon cancer cell lines and lung cancer cell lines.
Nathan Goodyear

The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic... - 0 views

www.ncbi.nlm.nih.gov/...PMC3962576

microglia LDN low dose naltrexone pain inflammation

shared by Nathan Goodyear on 05 Jul 17 - No Cached
  • orally active competitive opioid receptor antagonist
  • 4.5 mg, though the dosage can vary a few milligrams below or above that common value
  • At the low dosage level, naltrexone exhibits paradoxical properties, including analgesia and anti-inflammatory actions
  • ...10 more annotations...
  • LDN may be an effective treatment for FM
  • In addition to the antagonist effect on mu-opioid and other opioid receptors, naltrexone simultaneously has an antagonist effect on non-opioid receptors (Toll-like receptor 4 or TLR4) that are found on macrophages such as microglia
  • It is via the non-opioid antagonist path that LDN is thought to exert its anti-inflammatory effects
  • Once activated, microglia produce inflammatory and excitatory factors that can cause sickness behaviors such as pain sensitivity, fatigue, cognitive disruption, sleep disorders, mood disorders, and general malaise
  • The neuroprotective action appears to result when microglia activation in the brain and spinal cord is inhibited
  • By suppressing microglia activation, naloxone reduces the production of reactive oxygen species and other potentially neuroexcitatory and neurotoxic chemicals
  • suppressed TNF-alpha, IL-6, MCP-1, and other inflammatory agents in peripheral macrophages
  • individuals with greater ESR at baseline experienced a greater drop in pain when taking LDN
  • LDN has been reported to reduce not only self-reported pain in that condition but also objective markers of inflammation and disease severity
  • Naltrexone has also shown some promise in improving disease severity in multiple sclerosis
  • Nathan Goodyear on 05 Jul 17
     
    LDN maybe useful in treating chronic pain via anti-inflammatory effects on microglia.
Nathan Goodyear

Cancers | Free Full-Text | A Second WNT for Old Drugs: Drug Repositioning against WNT-D... - 0 views

www.mdpi.com/htm

cancer Niclosamide ivermectin Wnt

shared by Nathan Goodyear on 16 Apr 18 - No Cached
  • To date nearly half of known human tumors show a dysregulation of the WNT signaling pathway
  • It should be also noted that the WNT pathway is not exclusively employed during development or overactivated in cancer. In adults many healthy tissues rely on it for renewal and homeostasis maintenance, most notably the intestine, haematopoietic system, hair, bones and skin. Therefore one might expect adverse reactions in all these organ systems, which has indeed been observed for many WNT-targeting compounds upon attempts to push them into the clinics
  • The intestine seems to be the most vulnerable in this regard
  • ...8 more annotations...
  • Ivermectin inhibits proliferation of human colon cancer and lung cancer cells both in vitro and in vivo
  • The anti-proliferative action, affecting both the bulk tumor cells and CSCs, was linked in this study to inhibition of WNT signaling
  • the anti-WNT IC50 of ivermectin is 5–10 times (~1–2 µM vs. 10 µM) lower than that of its toxic effect against chloride channels
  • oral bioavailability of the drug, as for other antiparasitic drugs discussed in this section, is very low
  • Toxicity studies in vivo have also demonstrated a wide therapeutic index for ivermectin
  • Its anti-proliferative activity has been demonstrated in a wide array of cancer cell lines representative of WNT-dependent cancers: non-small lung carcinoma [96], multiple myeloma [97], hepatoma [98], adrenocortical carcinoma [99], ovarian cancer [100] and glioblastoma
  • Niclosamide inhibits the canonical WNT pathway
  • In addition to inhibiting the canonical WNT pathway, niclosamide may mediate its anticancer activities through several other signaling pathways such as NOTCH [107], MTOR [108], NF-κB [97] and STAT3 [96]
  • Nathan Goodyear on 16 Apr 18
     
    review article highlights older medications that have anti-Wnt pathway effects in cancer.  Roughly, 50% of cancer involve upregulated Wnt pathway activity. Other drugs of note: metformin
Rachel Renner

Superb Anti-Snoring Device - 1 views

Noiselezz is the best anti-snoring device that I have ever tried. My wife was about to kick me out of our bedroom until I have found KVG Australia's anti-snoring product. Honestly, I have already t...

started by Rachel Renner on 15 Oct 12 no follow-up yet
Nathan Goodyear

Estrogen Receptor β: Expression Profile and Possible Anti-Inflammatory Role i... - 0 views

jpet.aspetjournals.org/...83.full

ER-beta estrogen hormone hormones receptor inflammation anti-inflammatory asthma disease

shared by Nathan Goodyear on 11 Oct 12 - No Cached
  • Nathan Goodyear on 11 Oct 12
     
    ER-beta, known to have anti-inflammatory effects, not shown to have positive effect on asthma.
Nathan Goodyear

Incensole acetate, an incense component, elicits psychoactivity by activating TRPV3 cha... - 0 views

www.fasebj.org/...3024.full

Boswellia Frankincense anxiety depression essential oils brain

shared by Nathan Goodyear on 11 Apr 12 - No Cached
  • Nathan Goodyear on 11 Apr 12
     
    Boswellia shown to have potential anti-anxiety and anti-depressive properties.
Nathan Goodyear

Inflammation and insulin resistance 10.1016/j.febslet.2007.11.057 : FEBS Letters | Scie... - 0 views

www.sciencedirect.com/...S0014579307012082

inflammation insulin resistance IR PPAR TNF-alpha IL-6 IL-10 IL-1Beta JNK GLT-4 Resistin adiponectin Gherlin NF-kapppB iNOS lkkb obesity TLR-4

shared by Nathan Goodyear on 10 Jan 12 - No Cached
  • A subsequent study by Yuan et al. showed that Tnf treatment of 3T3L1 adipocytes induces insulin resistance and that this could be prevented by pretreatment of cells with aspirin
  • Activation of the Tnf receptor results in stimulation of NFκB signaling via Ikkb
  • Insulin is a pleiotropic hormone
  • ...25 more annotations...
  • the percentage of macrophages in a given adipose tissue depot is positively correlated with adiposity and adipocyte size
  • Il-10 is an anti-inflammatory cytokine produced by macrophages and lymphocytes
  • Il-10 exerts its anti-inflammatory activity by inhibiting Tnf-induced NFκB activation by reducing IKK activity [38]
  • adipose tissue macrophages are responsible for nearly all adipose tissue Tnf expression and a significant portion of Nos2 and Il6 expression
  • One theory holds that the expansion of adipose tissue leads to adipocyte hypertrophy and hyperplasia and that large adipocytes outstrip the local oxygen supply leading to cell autonomous hypoxia with activation of cellular stress pathways
  • The use of the anti-inflammatory compounds, salicylate and its derivative aspirin, for treating symptoms of T2DM dates back over 100 years
  • elevated levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin (IL-8) have all been reported in various diabetic and insulin resistant states
  • overnutrition and obesity are often accompanied by elevations in tissue and circulating FFA concentrations, and saturated FFAs can directly activate pro-inflammatory responses
  • Adipokines such as resistin, leptin and adiponectin, which are secreted by adipocytes, can also affect inflammation and insulin sensitivity
  • In skeletal muscle insulin promotes glucose uptake by stimulating translocation of the GLUT4 glucose transporter
  • macrophages are also capable of undergoing a phenotypic switch from an M1 state, which was defined as the “classically activated” pro-inflammatory macrophage, to the M2 state or the “alternatively activated” non-inflammatory cell
  • saturated fatty acids are the most potent inducers of this inflammatory response
  • Several inducers of insulin resistance, including FFAs, pro-inflammatory cytokines and oxidative stress, activate the expression of Nos2, the gene that encodes iNOS (reviewed in [33]
  • Adipose tissue insulin signaling results in decreased hormone sensitive lipase activity and this anti-lipolytic effect inhibits free fatty acid (FFA) efflux out of adipocytes.
  • In the liver, insulin inhibits the expression of key gluconeogenic enzymes and, therefore, insulin resistance in liver leads to elevated hepatic glucose production
  • elevated JNK activity in liver, adipose tissue and skeletal muscle of obese insulin resistant mice, and knockout of Jnk1 (Jnk1−/−) leads to amelioration of insulin resistance in high fat diet
  • Adipose tissue from obese mice contains proportionately more M1 macrophages, whereas, lean adipose tissue contains more M2 macrophages, and increased M1 content positively correlates with inflammation, macrophage infiltration and insulin resistance
  • C-reactive protein (CRP)
  • these studies highlight the possibility that increased iNOS activity plays a direct role in the pathogenesis of insulin resistance
  • the important role of Ikkb in the development of obesity and inflammation-induced insulin resistance.
  • It is probable that local concentrations of inflammatory mediators, such as FFAs, Tnf or other cytokines/adipokines contribute to this polarity switch
  • Tnf and other cytokines/chemokines are symptomatic of inflammation, and while they propagate and/or maintain the inflammatory state, they are not the initial cause(s) of inflammation
  • Tlr4, in particular, is stimulated by lipopolysaccharide (LPS), an endotoxin released by gram-negative bacteria
  • Tlr4 belongs to the family of Toll-like receptors that function as pattern recognition receptors that guard against microorganismal infections as part of the innate immune system.
  • Tlr4 stimulation results in the activation of both Ikkb/NFκB and JNK/AP-1 signaling, culminating in the expression and secretion of pro-inflammatory cytokines/chemokines, including, Il1b, IL-6, Tnf, Mcp1, etc. (reviewed in [57
  • Nathan Goodyear on 10 Jan 12
     
    Great review of all the known components in the inflammation, insulin resistance link
Nathan Goodyear

Effects of supplemental vitamin D and calcium on biomarkers of inflammation in colorect... - 0 views

www.spectracell.com/...calciumoncolorectaladenoma.pdf

inflammation cancer colorectal vitamin D3 CRP TNF IL-6 IL-1B IL-8

shared by Nathan Goodyear on 01 Feb 12 - No Cached
  • Nathan Goodyear on 01 Feb 12
     
    Vitamin D3 shown to reduce CRP, TNF, IL-6, IL-1B, IL-8 in colorectal adenoma patients. This study supports the anti-inflammatory, anti-cancer benefits of vitamin D3.
Nathan Goodyear

Activity and expression of progesterone metabolizing 5α-reductase, 20α-hydrox... - 0 views

www.ncbi.nlm.nih.gov/...PMC154104

progesterone metabolites breast cancer 5alpha-reductase 5-alpha pregnene 5-alpha pregnenes 4-pregnene 4-pregnenes

shared by Nathan Goodyear on 30 Jan 14 - No Cached
  • Exposure of human breast cell lines (MCF-7, MCF-10A, and ZR-75-1) to 5α-pregnanes results in changes associated with neoplasia, including increased proliferation and decreased attachment [1], depolymerization of F-actin [2] and decreases in adhesion plaque-associated vinculin
  • Exposure to 4-pregnenes results, in general, in opposite (anti-cancer-like) effects
  • 5αR1 has been detected in various androgen-independent organs, such as the liver and brain
  • ...10 more annotations...
  • 5αR2 has been found predominantly in androgen-dependent organs, such as epididymis and prostate
  • The 5α-pregnanes:4-pregnenes ratio was about 8-fold higher in tumorous than in nontumorous breast tissue after an 8-hour incubation with [14C]progesterone
  • Studies with breast cell lines, showing that 5α-pregnanes stimulate proliferation and decrease attachment of cells
  • both tissue and breast cell line studies suggest that an elevated level of progesterone 5α-reductase activity may be an indicator of breast tumorigenesis, regardless of presence or absence of ER and/or PR
  • 5αR1 is the main isoform expressed in human breast carcinomas [29] and that 5αR2 may not be associated with risk of breast cancer
  • the differences in 5α-pregnane production between the cells is due primarily to a difference in 5αR1 expression
  • As in the case of 5α-reductase activity, the presence or absence of ER and PR do not appear to be related to 5α-reductase expression.
  • the conversion of progesterone to the cancer promoting 5α-pregnanes is significantly higher in the human tumorigenic breast cell lines
  • lthough both 5αR1 and 5αR2 are expressed by these cells, the elevated 5α-reductase activity appears to be the result of significantly greater expression of 5αR1
  • Changes in progesterone metabolizing enzyme expression (resulting in enzyme activity changes) may be responsible for promoting breast cancer progression due to increased production of tumor-promoting 5α-pregnanes and decreased production of anti-cancer 20α – and 3α-4-pregnenes
  • Nathan Goodyear on 30 Jan 14
     
    balance of enzyme production between 5alpha-reductase and 20alpha-hydroxysteroid oxidoreductase and 3alpha(beta)-hydroxysteroid oxidoreductase play role in carcinogenesis and proliferation in the balance of production of progesterone metabolites. The 5alpha pregnenes are pro carcinogenic  and the 4-pregnenes are anti carcinogenic.
Nathan Goodyear

Clinical and Pathological Roles of Ro/SSA Autoantibody System - 0 views

www.hindawi.com/...606195

Anti-SSA antibodies Anti-Ro Lupus Sjogren's syndrome autoimmune disease

shared by Nathan Goodyear on 12 Aug 13 - No Cached
  • Nathan Goodyear on 12 Aug 13
     
    Clinical use of anti-SSA antibodies.  Most commonly linked with Lupus and Sjogren's syndrome.  
Nathan Goodyear

Perspectives on sesquiterpene lactones in ... [Curr Drug Targets. 2011] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...21561425

sesquiterpenes inflammation cancer

shared by Nathan Goodyear on 01 Dec 13 - No Cached
  • Nathan Goodyear on 01 Dec 13
     
    sespquiterpenes show anti-inflammatory and anti-cancer effects.
wheelchairindia9

Choosing Correct Power wheel chair - 0 views

www.apsense.com/...correct-power-wheel-chair.html

Choosing Correct Power wheel chair Electric Power Wheel Chair folding or rigid design comfortable seating moving freely Life Mobility Center convenient to transport

shared by wheelchairindia9 on 22 Apr 15 - No Cached
  • wheelchairindia9 on 22 Apr 15
     
    Power wheel chair is one type of wheel chairs which is also referred and known as Electric Power Wheel Chair or (EPW). An Power wheel chair is used to move such wheel chairs instead of pushing by some attendant or by hand rims. It also has navigational controls so that it can be moved to any desired direction. Power wheel chairs are suitable for those, who are weaker to move the manual wheel chair using the hand rims and also provides its users a level of comfort. The user can control its speed and direction by a joystick sort of control while sitting on the chair. There are many different types of Power wheel chair and finding the appropriate one will depend on each individual's medical condition. Wheelchairs can be manual or electrically powered. Manual wheelchairs can come in either a folding or rigid design. Rigid type wheelchairs tend to be lighter and more easily maneuvered and should be used by more active wheelchair users. Folding wheelchairs would be an excellent choice for individuals needing to use the wheelchair for travel on a frequent basis. Many people have disabilities that make it difficult to propel themselves in a manual wheelchair and in this situation an electrically powered wheelchair may prove more useful. Power chairs are little bit more complex and the user can control it with minimum effort. This kind of chair will give extraordinary maneuverability, stability and power and it is perfect for people who want more from their wheelchairs. Better Life Mobility Center offers various models, so sure that won't have problem to choose one that will suit completely. All the power chairs that offer are the result of the extensive research and designed with the user's needs in mind. Karma latest power standing wheelchair is now available in India. Power Wheelchairs For Sale - Increase freedom Stand up again improve independence and be find of body. Karma KP 10.2 Power Wheelchair: Features: Seat, base & battery quickly detach f
wheelchairindia9

Choosing Correct Power wheel chair - 0 views

www.articlepoint.org/...correct-power-wheel-chair.aspx

Choosing Correct Power wheel chair Electric Power Wheel Chair folding or rigid design comfortable seating moving freely Life Mobility Center convenient to transport

shared by wheelchairindia9 on 23 Apr 15 - No Cached
  • wheelchairindia9 on 23 Apr 15
     
    Power wheel chair is one type of wheel chairs which is also referred and known as Electric Power Wheel Chair or (EPW). An Power wheel chair is used to move such wheel chairs instead of pushing by some attendant or by hand rims. It also has navigational controls so that it can be moved to any desired direction. Power wheel chairs are suitable for those, who are weaker to move the manual wheel chair using the hand rims and also provides its users a level of comfort. The user can control its speed and direction by a joystick sort of control while sitting on the chair. There are many different types of Power wheel chair and finding the appropriate one will depend on each individual's medical condition. Wheelchairs can be manual or electrically powered. Manual wheelchairs can come in either a folding or rigid design. Rigid type wheelchairs tend to be lighter and more easily maneuvered and should be used by more active wheelchair users. Folding wheelchairs would be an excellent choice for individuals needing to use the wheelchair for travel on a frequent basis. Many people have disabilities that make it difficult to propel themselves in a manual wheelchair and in this situation an electrically powered wheelchair may prove more useful. Power chairs are little bit more complex and the user can control it with minimum effort. This kind of chair will give extraordinary maneuverability, stability and power and it is perfect for people who want more from their wheelchairs. Better Life Mobility Center offers various models, so sure that won't have problem to choose one that will suit completely. All the power chairs that offer are the result of the extensive research and designed with the user's needs in mind. Karma latest power standing wheelchair is now available in India. Power Wheelchairs For Sale - Increase freedom Stand up again improve independence and be find of body. Karma KP 10.2 Power Wheelchair: Features: Seat, base & battery quickly detach f
wheelchairindia9

Choosing Correct Power wheel chair - 0 views

www.blogroll.net/article.php

Choosing Correct Power wheel chair Electric Power Wheel Chair folding or rigid design comfortable seating moving freely Life Mobility Center convenient to transport

shared by wheelchairindia9 on 25 Apr 15 - No Cached
  • wheelchairindia9 on 25 Apr 15
     
    Power wheel chair is one type of wheel chairs which is also referred and known as Electric Power Wheel Chair or (EPW). An Power wheel chair is used to move such wheel chairs instead of pushing by some attendant or by hand rims. It also has navigational controls so that it can be moved to any desired direction. Power wheel chairs are suitable for those, who are weaker to move the manual wheel chair using the hand rims and also provides its users a level of comfort. The user can control its speed and direction by a joystick sort of control while sitting on the chair. There are many different types of Power wheel chair and finding the appropriate one will depend on each individual's medical condition. Wheelchairs can be manual or electrically powered. Manual wheelchairs can come in either a folding or rigid design. Rigid type wheelchairs tend to be lighter and more easily maneuvered and should be used by more active wheelchair users. Folding wheelchairs would be an excellent choice for individuals needing to use the wheelchair for travel on a frequent basis. Many people have disabilities that make it difficult to propel themselves in a manual wheelchair and in this situation an electrically powered wheelchair may prove more useful. Power chairs are little bit more complex and the user can control it with minimum effort. This kind of chair will give extraordinary maneuverability, stability and power and it is perfect for people who want more from their wheelchairs. Better Life Mobility Center offers various models, so sure that won't have problem to choose one that will suit completely. All the power chairs that offer are the result of the extensive research and designed with the user's needs in mind. Karma latest power standing wheelchair is now available in India. Power Wheelchairs For Sale - Increase freedom Stand up again improve independence and be find of body. Karma KP 10.2 Power Wheelchair: Features: Seat, base & battery quickly detach f
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