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Nathan Goodyear

LRRK2 G2019S Impairs Chaperone-Mediated Autophagy in Neurons (S13.003) -- Kuo et al. 80... - 0 views

www.neurology.org/...S13.003

Parkinsons disease neurology Lewy Bodies Chaperone-mediated autophagy

shared by Nathan Goodyear on 01 Jun 13 - No Cached
  • Nathan Goodyear on 01 Jun 13
     
    impaired auto destruction process leads to the Lewy bodies found in Parkinson's disease.
Nathan Goodyear

Testosterone: a metabolic hormone in health and disease - 0 views

joe.endocrinology-journals.org/...R25.full

male hormone hormones testosterone hypogonadal-obesity-adipocytokine hypothesis

shared by Nathan Goodyear on 08 May 13 - No Cached
  • E2 and the inflammatory adipocytokines tumour necrosis factor α (TNFα) and interleukin 6 (IL6) inhibit hypothalamic production of GNRH and subsequent release of LH and FSH from the pituitary
  • Leptin, an adipose-derived hormone with a well-known role in regulation of body weight and food intake, also induces LH release under normal conditions via stimulation of hypothalamic GNRH neurons
  • In human obesity, whereby adipocytes are producing elevated amounts of leptin, the hypothalamic–pituitary axis becomes leptin resistant
  • ...39 more annotations...
  • there is evidence from animal studies that leptin resistance, inflammation and oestrogens inhibit neuronal release of kisspeptin
  • Beyond hypothalamic action, leptin also directly inhibits the stimulatory action of gonadotrophins on the Leydig cells of the testis to decrease testosterone production; therefore, elevated leptin levels in obesity may further diminish androgen status
  • Prostate cancer patients with pre-existing T2DM show a further deterioration of insulin resistance and worsening of diabetic control following ADT
  • ADT for the treatment of prostatic carcinoma in some large epidemiological studies has been shown to be associated with an increased risk of developing MetS and T2DM
  • Non-diabetic men undergoing androgen ablation show increased occurrence of new-onset diabetes and demonstrate elevated insulin levels and worsening glycaemic control
  • increasing insulin resistance assessed by glucose tolerence test and hypoglycemic clamp was shown to be associated with a decrease in Leydig cell testosterone secretion in men
  • The response to testosterone replacement of insulin sensitivity is in part dependent on the androgen receptor (AR)
  • Low levels of testosterone have been associated with an atherogenic lipoprotein profile, characterised by high LDL and triglyceride levels
  • a positive correlation between serum testosterone and HDL has been reported in both healthy and diabetic men
  • up to 70% of the body's insulin sensitivity is accounted for by muscle
  • Testosterone deficiency is associated with a decrease in lean body mass
  • relative muscle mass is inversely associated with insulin resistance and pre-diabetes
  • GLUT4 and IRS1 were up-regulated in cultured adipocytes and skeletal muscle cells following testosterone treatment at low dose and short-time incubations
  • local conversion of testosterone to DHT and activation of AR may be important for glucose uptake
  • inverse correlation between testosterone levels and adverse mitochondrial function
  • orchidectomy of male Wistar rats and associated testosterone deficiency induced increased absorption of glucose from the intestine
  • (Kelley & Mandarino 2000). Frederiksen et al. (2012a) recently demonstrated that testosterone may influence components of metabolic flexibility as 6 months of transdermal testosterone treatment in aging men with low–normal bioavailable testosterone levels increased lipid oxidation and decreased glucose oxidation during the fasting state.
  • Decreased lipid oxidation coupled with diet-induced chronic FA elevation is linked to increased accumulation of myocellular lipid, in particular diacylglycerol and/or ceramide in myocytes
  • In the Chang human adult liver cell line, insulin receptor mRNA expression was significantly increased following exposure to testosterone
  • Testosterone deprivation via castration of male rats led to decreased expression of Glut4 in liver tissue, as well as adipose and muscle
  • oestrogen was found to increase the expression of insulin receptors in insulin-resistant HepG2 human liver cell line
  • FFA decrease hepatic insulin binding and extraction, increase hepatic gluconeogenesis and increase hepatic insulin resistance.
  • Only one, albeit large-scale, population-based cross-sectional study reports an association between low serum testosterone concentrations and hepatic steatosis in men (Völzke et al. 2010)
  • This suggests that testosterone may confer some of its beneficial effects on hepatic lipid metabolism via conversion to E2 and subsequent activation of ERα.
  • hypogonadal men exhibiting a reduced lean body mass and an increased fat mass, abdominal or central obesity
  • visceral adipose tissue was inversely correlated with bioavailable testosterone
  • there was no change in visceral fat mass in aged men with low testosterone levels following 6 months of transdermal TRT, yet subcutaneous fat mass was significantly reduced in both the thigh and the abdominal areas when analysed by MRI (Frederiksen et al. 2012b)
  • ADT of prostate cancer patients increased both visceral and subcutaneous abdominal fat in a 12-month prospective observational study (Hamilton et al. 2011)
  • Catecholamines are the major lipolysis regulating hormones in man and regulate adipocyte lipolysis through activation of adenylate cyclase to produce cAMP
  • deficiency of androgen action decreases lipolysis and is primarily responsible for the induction of obesity (Yanase et al. 2008)
  • may be some regional differences in the action of testosterone on subcutaneous and visceral adipose function
  • proinflammatory adipocytokines IL1, IL6 and TNFα are increased in obesity with a downstream effect that stimulates liver production of CRP
  • observational evidence suggests that IL1β, IL6, TNFα and CRP are inversely associated with serum testosterone levels in patients
  • TRT has been reported to significantly reduce these proinflammatory mediators
  • This suggests a role for AR in the metabolic actions of testosterone on fat accumulation and adipose tissue inflammatory response
  • testosterone treatment may have beneficial effects on preventing the pathogenesis of obesity by inhibiting adipogenesis, decreasing triglyceride uptake and storage, increasing lipolysis, influencing lipoprotein content and function and may directly reduce fat mass and increase muscle mass
  • Early interventional studies suggest that TRT in hypogonadal men with T2DM and/or MetS has beneficial effects on lipids, adiposity and parameters of insulin sensitivity and glucose control
  • Evidence that whole-body insulin sensitivity is reduced in testosterone deficiency and increases with testosterone replacement supports a key role of this hormone in glucose and lipid metabolism
  • Impaired insulin sensitivity in these three tissues is characterised by defects in insulin-stimulated glucose transport activity, in particular into skeletal muscle, impaired insulin-mediated inhibition of hepatic glucose production and stimulation of glycogen synthesis in liver, and a reduced ability of insulin to inhibit lipolysis in adipose tissue
  • Nathan Goodyear on 08 May 13
     
    Great review of the Hypogonadal-obesity-adipocytokine hypothesis.
Nathan Goodyear

Estriol and Progesterone: A New Role for Sex Hormones - 0 views

www.ncbi.nlm.nih.gov/...PMC3614637

Estriol Progesterone autoimmune disease inflammation hormones

shared by Nathan Goodyear on 09 May 16 - No Cached
  • Pregnancy-associated Th2 shift has been proposed as a mechanism underlying the improvement of Th1-mediated autoimmune diseases (as rheumatoid arthritis, multiple sclerosis (MS), autoimmune thyoriditis, uveitis, and psoriatic arthritis
  • Th2-mediated autoimmune diseases (as systemic lupus erythematosus)
  • During pregnancy PRG serum level increases by a factor of 4, while estrogen estriol (E3) serum concentration increases by a factor of 20
  • ...1 more annotation...
  • In pregnant women at or near term there is a daily production of about 300 μmol (80 mg) of E3 and 1 mmol (300 mg) of PRG
  • Nathan Goodyear on 09 May 16
     
    Estriol and Progesterone associated, as found with pregnancy, associated with decrease in Th1 autoimmune disease.
Nathan Goodyear

Immune Modulation in Multiple Sclerosis Patients Treated with the Pregnancy Hormone Est... - 0 views

www.jimmunol.org/...6267.long

MS RA rheumatoid arthritis psoriasis multiple sclerosis Estriol autoimmune disease inflammation hormone hormones E3

shared by Nathan Goodyear on 19 Mar 14 - No Cached
  • A beneficial effect of pregnancy on clinical symptoms has been observed in MS and other Th1-mediated autoimmune diseases, including rheumatoid arthritis (RA), psoriasis, uveitis, and thyroiditis
  • In general, Th1 lymphocytes secrete proinflammatory cytokines (e.g., IL-2, IL-12, IFN-γ, and TNF-α) that promote cellular immunity, while Th2 lymphocytes produce anti-inflammatory cytokines (e.g., IL-4, IL-5, IL-6, and IL-10) that promote humoral immunity
  • Th2 cytokines are associated with the down-regulation of Th1 cytokines and may confer protection from Th1-mediated autoimmune diseases
  • ...1 more annotation...
  • During pregnancy, there is a shift from Th1 to Th2 that occurs both locally, at the fetal maternal interface, (23, 24, 25), and systemically
  • Nathan Goodyear on 19 Mar 14
     
    MS is in part a Th1 autoimmune disease.  Estriol therapy induces a shift to Th2 through increase in Th10.  Estriol also decreases TNF-alpha cytokine production.
Nathan Goodyear

New roles for estrogens in rheumatoid arthritis. - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...14740444

RA rheumatoid arthritis estradiol inflammation NF-kapppB

shared by Nathan Goodyear on 09 May 16 - No Cached
  • Nathan Goodyear on 09 May 16
     
    Estradiol appears to be pro-inflammatory in the synovial fluids of men/women with RA.  This appears to be mediated through NF-KappaB.
Nathan Goodyear

T-cell subsets (Th1 versus Th2). - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...10923599

interleukins Th1 Th2 immune system autoimmune disease CD4 CD8

shared by Nathan Goodyear on 11 Jan 17 - No Cached
  • Nathan Goodyear on 11 Jan 17
     
    only abstract available: Review of the cell mediated immune system and the interleukin signaling.
Nathan Goodyear

Gender and sex hormones in multiple sclerosis pathology and therapy - 0 views

www.ncbi.nlm.nih.gov/...PMC2689399

hormones MS multiple Sclerosis Estriol progesterone

shared by Nathan Goodyear on 11 Jan 17 - No Cached
  • It is now well recognized that the disease manifestation is reduced in pregnant women with relapsing-remitting MS
  • This occurs particularly during the third trimester when levels of estrogens (estradiol and estriol) and progesterone (see Table 2) are elevated up to about 20 times
  • This seems well correlated with a decrease in active white matter lesions detected by MRI
  • ...12 more annotations...
  • This clinical improvement is however followed by temporary rebound exacerbations at post-partum, when the hormone levels decline
  • a shift from Th1 to Th2 immune response, expansion of suppressive regulatory T lymphocytes and decrease in the number of circulating CD16+ natural killer (NK)-cells
  • Th1 lymphocytes secrete proinflammatory cytokines (e.g. IL-2, IFNgamma, lymphotoxin) while Th2 cells secrete anti-inflammatory cytokines (e.g. IL-4, IL-5, IL-10), which favor humoral-mediated responses
  • Th2 cytokines are associated with down-regulation of Th1 cytokines and this Th2 shift is believed to provide protection from allograft rejection during pregnancy as well as from Th1-mediated autoimmune disease
  • it is worth noting that the levels of other hormones with anti-inflammatory activity (1,25-dihydroxy-vitamin D3, norepinephrine, cortisol) also increase by 2 to 4 times during late pregnancy
  • 1,25-dihydroxy vitamin D3 induces regulatory T-cell function important for development of self-tolerance
  • breast-feeding does not alter the relapse rate in women with MS
  • Leptin is a pleiotropic hormone produced primarily by adipocytes but also by T lymphocytes and neurons
  • Several lines of evidence indicate that leptin contributes to EAE/MS pathogenesis, influencing its onset and clinical severity, by acting as a proinflammatory cytokine which promotes regulatory T cell (Treg) anergy and hyporesponsiveness, resulting in increased Th1 (TNFalpha, INFgamma) and reduced Th2 (IL-4) cytokine production
  • circulating leptin levels are increased in relapsing-remitting MS patients (men and women analyzed together) while the CD4+CD25+Treg population decreases
  • As the leptin plasma concentrations are proportional to the amount of fat tissue, obese/overweight individuals produce higher levels of leptin
  • Nielsen et al found that estradiol and progesterone exert neuroprotection against glutamate neurotoxicity, while MPA antagonizes the neuroprotective effect of estradiol and exacerbated neuron death induced by glutamate excitotoxicity
  • Nathan Goodyear on 11 Jan 17
     
    very good review of the differences in MS and hormones between the sexes.
Nathan Goodyear

Duration of intralipid's suppressive eff... [Am J Reprod Immunol. 2008] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...18782287

intralipid therapy natural killer cells NK infertility reproduction reproductive failure

shared by Nathan Goodyear on 16 Apr 12 - No Cached
  • Nathan Goodyear on 16 Apr 12
     
    Intralipid therapy effect in treating natural killer cell overactivity in those women that have immune mediated recurrent pregnancy loss.
Nathan Goodyear

Direct and Indirect Inhibition of Th1 Development by Progesterone and Glucocorticoids - 0 views

www.jimmunol.org/...1087.abstract

progesterone immune system Th1 Th2

shared by Nathan Goodyear on 20 Apr 12 - No Cached
  • Nathan Goodyear on 20 Apr 12
     
    Progesterone found to modulate the immune system.  Progesterone decreases Th1 activity to increase Th2.  This has significant immune mediated disorders/disease.
Nathan Goodyear

Endogenous Estrogens Influence Endothelial Function in Young Men - 0 views

circres.ahajournals.org/...1127.long

aromatase inhibition anastrozole arimidex men

shared by Nathan Goodyear on 25 Apr 12 - No Cached
  • Nathan Goodyear on 25 Apr 12
     
    aromatase inhibition with anastrozole, in this study, resulted in impaired flow mediated dilation.  No resultant change in inflammatory markers were seen.  Again, my problem with this study is the use of serum for the hormone evaluation.  I would bet not enough aromatase inhibition was provided.
Nathan Goodyear

Cortisol, Testosterone, and Coronary Heart Disease - 0 views

www.cenegenicsfoundation.org/..._From_The_Caerphilly_Study.pdf

cortisol:testosterone cortisol testosterone ischemic heart disease CVD CAD insulin resistance cardiovascular disease

shared by Nathan Goodyear on 29 Jun 12 - No Cached
  • Nathan Goodyear on 29 Jun 12
     
    Cortisol:Testosterone ratio associated with statistical increase risk of ischemic heart disease. This was mediated through the insulin resistance.
Nathan Goodyear

thyroid disease and the heart - 0 views

www.ncbi.nlm.nih.gov/...v084p00455.pdf

thyroid disease heart T3 T4 thyroxine try-idodothyronine

shared by Nathan Goodyear on 31 Jan 12 - No Cached
  • Nathan Goodyear on 31 Jan 12
     
    nice review of how thyroid disease effects cardiac function. Notice the author of this paper describes "thy- roxine (T4) which is a prohormone and tri-iodothyronine (T3) which acts as the final mediator".
Nathan Goodyear

Estrogen receptor (ER) β, a modulator of ERα in the uterus - 0 views

www.pnas.org/...5936.full

receptors ER-alpha ER-beta hormones hormone

shared by Nathan Goodyear on 16 Aug 12 - No Cached
  • induction of PR is an ERα-mediated event and repression of epithelial PR is ERβ mediated.
  • Nathan Goodyear on 16 Aug 12
     
    ER alpha and ER beta have different effects on the uterus in this mice model.  ER beta modulates ER alpha.  ER beta decreases PR, whereas ER alpha increases PR.
Nathan Goodyear

Comparative Studies of the Estrogen Receptors β and α and the Androgen Recept... - 0 views

ajp.amjpathol.org/...fulltext

ER beta ER-beta AR androgen receptors ER alpha ER-alpha prostate disease cancer estrogen receptor hormone hormones men male

shared by Nathan Goodyear on 21 Jan 14 - No Cached
  • ER-β is predominately immunolocalized in basal cells and to a lesser extent in stromal cells of the morphologically normal human prostate
  • ER-α is detected in stromal cells and rarely in basal cells of the normal gland
  • AR was predominately localized in the nuclei of differentiated secretory cells and variably in basal cells of the normal acinar/duct unit as well as in stromal cells
  • ...9 more annotations...
  • Hall and colleagues44 have reported that ER-β functions as a transdominant inhibitor of ER-α transcription and that it acts to decrease overall cellular sensitivity to estradiol
  • The expression of ER-β was diminished in high-grade dysplasias when compared to normal glands and lower grade lesions.
  • The transition from normal to low/moderate dysplastic glands in the peripheral zone was marked by the appearance of ER-β homogeneously immunostained nuclei in secretory as well as basal cells with no changes in the localization of the other receptors.
  • proliferative signals mediated by AR in basal cells or by ER-α and AR in stromal cells may be opposed by the purported growth-inhibitory action of ER-β25, 26, 27, 28 localized in basal cells.
  • The diminution of ER-β expression in high-grade dysplasias and grade 4/5 cancers may be therefore related to the alteration of DNA methylation pattern in CpG islands of the promoter, resulting in down-regulation of the receptor at the transcriptional level
  • based on the proposed anti-proliferative function of the receptor,25, 26, 27, 28 the presence of ER-β in secretory cells of low/moderate-grade lesions may represent a transient abortive attempt to counter growth of these cells
  • the attrition of receptor-positive basal cells in the high-grade dysplasias may signify a continuing loss of growth inhibitory function mediated by ER-β in these precursor lesions
  • Our findings in prostate therefore differ from those reported for human colon cancer in which Folley and colleagues48 demonstrated that a selective loss of ER-β protein but not receptor message expression occurs in these neoplasms
  • Our findings therefore differed from those of Bonkhoff and colleagues33 who found immunostaining for the receptor in high-grade dysplasias and grade 4/5 carcinomas. Using in situ hybridization these authors also reported that a high percentage of dysplasias and carcinomas in their study contained cells that expressed ER-α message
  • Nathan Goodyear on 21 Jan 14
     
    Very nice study.  The authors looked at normal prostate, early disease and late stage prostate cancer.  The authors found that ER beta expression, as a general rule, was lost as progression occurred to the high-grade dysplasias and grad 4/5 carcinomas of the prostate.  Early low/moderate dysplasia was associated with an increase in ER beta--the authors propose that this was due to an attempt of the basal epithelium to counter the paracrine effect of ER alpha.   In contrast, androgen receptors appeared to be equally expressed across all.
Nathan Goodyear

Estrogen attenuates glutamate-induced cell death by inhibiting Ca2+ influx through L-ty... - 0 views

www.ncbi.nlm.nih.gov/...PMC2700344

estrogen estradiol apoptosis neurodegeneration glutamate glutamic acid

shared by Nathan Goodyear on 10 Mar 14 - No Cached
  • Nathan Goodyear on 10 Mar 14
     
    Estradiol inhibits glutamate mediated influx of calcium and thus cell death in cell line.  Glutamate, the principle excitatory neurotransmitter, is involved in neurodegeneration through activation of calcium channels.  This study of cell line cultures found that Estradiol inhibits this process.  I question whether this is applicable to both men and women.  Time will tell.
Nathan Goodyear

Methylmercury induces oxidative injury, alterations in permeability and glutamine trans... - 0 views

www.ncbi.nlm.nih.gov/...PMC1847599

methylmercury mercury astrocytes glutamate mitochondria brain inflammation oxidative ROS

shared by Nathan Goodyear on 26 Nov 13 - No Cached
  • Nathan Goodyear on 26 Nov 13
     
    methylmercury mediates neurotoxicity via mitochondrial damage, inflammation, and oxidative stress.  Astrocytes accumulated the methyl mercury.  The destruction of the astrocytes will result in an increase in glutamate.  Methylmercury is synergistic with other toxins in the development of immunoexcitotoxicity.
Nathan Goodyear

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

www.ncbi.nlm.nih.gov/...11378050

IC interstitial cystitis histamine bladder

shared by Nathan Goodyear on 12 May 15 - No Cached
  • Nathan Goodyear on 12 May 15
     
    Interstitial Cystitis is a histamine mediated inflammatory process.
Nathan Goodyear

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

www.ncbi.nlm.nih.gov/...2750582

IC interstitial cystitis histamine mast cells bladder

shared by Nathan Goodyear on 12 May 15 - No Cached
  • Nathan Goodyear on 12 May 15
     
    Interstitial cystitis is a histamine/mast cell mediated event.
Nathan Goodyear

Chronic Inflammation and Cytokines in the Tumor Microenvironment - 0 views

www.hindawi.com/...149185

inflammation cytokines tumor cancer inflammatory IL-6 IL-10 TNF-alpha

shared by Nathan Goodyear on 26 Jun 15 - No Cached
  • Nathan Goodyear on 26 Jun 15
     
    Acute inflammation is a response to an alteration induced by a pathogen or a physical or chemical insult, which functions to eliminate the source of the damage and restore homeostasis to the affected tissue. However, chronic inflammation triggers cellular events that can promote malignant transformation of cells and carcinogenesis. Several inflammatory mediators, such as TNF-α, IL-6, TGF-β, and IL-10, have been shown to participate in both the initiation and progression of cancer. In this review, we explore the role of these cytokines in important events of carcinogenesis, such as their capacity to generate reactive oxygen and nitrogen species, their potential mutagenic effect, and their involvement in mechanisms for epithelial mesenchymal transition, angiogenesis, and metastasis. Finally, we will provide an in-depth analysis of the participation of these cytokines in two types of cancer attributable to chronic inflammatory disease: colitis-associated colorectal cancer and cholangiocarcinoma.
Nathan Goodyear

Cell - GPR120 Is an Omega-3 Fatty Acid Receptor Mediating Potent Anti-inflammatory and ... - 0 views

www.cell.com/...S0092-8674(10)00888-3

Omega-3 DHA EPA insulin resistance Diabetes

shared by Nathan Goodyear on 15 Feb 11 - No Cached
  • ω-3 FA receptor/sensor and mediates potent insulin sensitizing and antidiabetic effects in vivo
  • Nathan Goodyear on 15 Feb 11
     
    Omega-3 improves insulin sensitivity
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