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seth morris

Feeling the Gyrating Beat with Herbal Highs - 1 views

Dancing in club parties is one way of relieving stress contained for many hours while working in the office. My friends and I love to spend an all-night party in order to unwind and forget the dead...

legal highs

started by seth morris on 09 May 11 no follow-up yet
Nathan Goodyear

Exposure to Bisphenol A Prenatally or in Adulthood Promotes TH2 Cytokine Production Associated with Reduction of CD4+CD25+ Regulatory T Cells - 0 views

www.ncbi.nlm.nih.gov/...PMC2290985

BPA plastics endocrine disruptor immune T reg cells

shared by Nathan Goodyear on 01 Jul 11 - No Cached
  • BPA promotes the development of TH2 cells in adulthood and both TH1 and TH2 cells in prenatal stages by reducing the number of regulatory T cells.
  • Bisphenol A (BPA), an estrogenic endocrine-disrupting chemical (EDC
  • BPA is one of the most widespread EDCs.
  • ...12 more annotations...
  • BPA antagonizes the actions of thyroid hormone
  • Prenatal exposure to BPA has been shown to alter a variety of reproductive endocrine parameters, such as testosterone and luteinizing hormone levels
  • arly onset of sexual maturation of female mice
  • imbalanced T-helper (TH)1/TH2 immune responses have been demonstrated on exposure to BPA
  • indicating that BPA exerted its effects by reducing the number of Treg cells.
  • Exposure to BPA by subcutaneous injection in adulthood significantly promoted antigen-stimulated production of IL-4, IL-10, and IL-13 in TH2-skewed
  • BPA can leak from the placenta and accumulate in the fetus
  • We showed that prenatal exposure to BPA increased the production of a TH1 cytokine, IFN-γ, and a TH2 cytokine, IL-4, after the offspring developed, suggesting that prenatal exposure to BPA can induce persistent immunologic effects lasting into adulthood.
  • These results are consistent with a previous report that fetal exposure to BPA augmented TH1 and TH2 immune responses
  • our results clearly demonstrate that the production of TH2 cytokines is promoted by BPA in adult mice and in offspring during developmental exposure.
  • The decrease of Treg cells would predispose to immune dysfunction in aged individuals, explaining their higher risk of immune-mediated diseases, cancer, and infections.
  • BPA might cause these diseases. Thus, avoiding exposure to or promoting the excretion of BPA and other EDCs would help in preventing diseases and adverse health effects.
  • Nathan Goodyear on 01 Jul 11
     
    BPA as endocrine disruptor and as immune disruptor
Nathan Goodyear

Sensitivity and specificity of six tests for the diagnosis of adult... - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...11994342

HGH GH human growth hormone IGF-1 growth hormone

shared by Nathan Goodyear on 04 Nov 14 - No Cached
  • ARG plus GHRH test, high sensitivity (96 and 95%, respectively) and specificity (92 and 91%, respectively) for GH deficiency were achieved
  • The greatest diagnostic accuracy occurred with the ITT and the ARG plus GHRH test
  • 95% specificity could be achieved with the ARG plus L-DOPA and ARG tests only with very low peak GH cut-points (0.25 and 0.21 microg/liter, respectively) and not at all with the L-DOPA test
  • ...1 more annotation...
  • Although serum IGF-I levels provided less diagnostic discrimination than all five GH stimulation tests, a value below 77.2 microg/liter was 95% specific for GH deficiency
  • Nathan Goodyear on 04 Nov 14
     
    study evaluated 6 tests for HGH deficiency diagnosis.  Ninety-five percent specificity found with ARG + l-DOPA and ARG alone.  However, the authors found a 95% specificity with IGF-1 < 77.  Although, IGF-1 is false negative in up to 65% of those with HGH deficiency.
Nathan Goodyear

Nutrition & Metabolism | Full text | Over-stimulation of insulin/IGF-1 signaling by Western diet may promote diseases of civilization: lessons learnt from Laron syndrome - 0 views

www.nutritionandmetabolism.com/...41

cancer nutrition diet sugar carbohydrates insulin IGF-1 acne insulin resistance western diet

shared by Nathan Goodyear on 09 Dec 14 - No Cached
  • Nathan Goodyear on 09 Dec 14
     
    Elevated insulin and IGF-1 as a result of the typical western diet results in increased risk of many of the chronic diseases of aging that we see in America--cancer.
Nathan Goodyear

Anti-Inflammatory Effects of Progesterone in Lipopolysaccharide-Stimulated BV-2 Microglia - 0 views

www.ncbi.nlm.nih.gov/...PMC4117574

progesterone inflammation TNF-alpha NF-kappaB hormone hormones LPS microglia

shared by Nathan Goodyear on 29 Aug 14 - No Cached
  • Nathan Goodyear on 29 Aug 14
     
    Progesterone and its anti-inflammatory effects.
Nathan Goodyear

PPARγ and human metabolic disease - 0 views

www.ncbi.nlm.nih.gov/...PMC1386124

PPAR-gamma perioxisome proliferator-activated receptor disease PPAR

shared by Nathan Goodyear on 24 Jan 13 - No Cached
  • PPARα and PPARδ appear primarily to stimulate oxidative lipid metabolism
  • PPARγ is principally involved in the cellular assimilation of lipids via anabolic pathways
  • PPARs are members of the nuclear hormone receptor superfamily
  • ...7 more annotations...
  • Expression of PPARγ is highest in adipose tissue,
  • PPARγ also plays a key role in the entraining of adipose tissue lipid metabolism to nutritional state
  • Its expression is highest postprandially
  • its activation leads to upregulation of genes that mediate FA uptake and trapping
  • PPARγ may also promote futile cycling in adipocytes between triglyceride (TG) esterification and de-esterification
  • its high expression in macrophages, which are now known to infiltrate the dysfunctional adipose tissue of obese subjects
    • Nathan Goodyear
      Nathan Goodyear on 28 Aug 14
       
      PPAR gamma is associated with adipocyte differentiation and lipid storage.
  • Nathan Goodyear on 24 Jan 13
     
    review of PPAR gamma
  • Blu Electronic Cigarettes on 03 Sep 14
     
    very informative! Thanks for sharing!
Nathan Goodyear

The kisspeptin-GnRH pathway in human reproductive health and disease - 0 views

humupd.oxfordjournals.org/...humupd.dmu009.full

kisspeptin kisspeptins hormones leptin hormone

shared by Nathan Goodyear on 04 Sep 14 - No Cached
  • Kisspeptin stimulates LH secretion in healthy men (filled squares) and women
  • This raises the possibility that diminished kisspeptin secretion is a potential mechanism for hypogonadotropic hypogonadism in patients with obesity and diabetes
  • The likely pathways for down-regulation of kisspeptin signalling include negative feedback by estrogen, which is markedly elevated in obesity (Schneider et al., 1979), resistance to leptin, also seen in human obesity (Finn et al., 1998), insulin resistance and hyperglycaemia (Castellano et al., 2006, 2009), and inflammation, which is up-regulated in hypogonadal men with diabetes (Dandona et al., 2008) and is associated with decreased kisspeptin expression in rats
  • Nathan Goodyear on 04 Sep 14
     
    Very nice, updated review of kisspeptins, hormone production and the negative/positive effects of kisspeptins.
Nathan Goodyear

http://www.hairlosshelp.com/pdf/insulin.pdf - 0 views

www.hairlosshelp.com/...insulin.pdf

insulin SHBG Testosterone male men hormone hormones obese obesity

shared by Nathan Goodyear on 03 Mar 15 - No Cached
  • Nathan Goodyear on 03 Mar 15
     
    Men with Obesity are found to have lower SHBG and Testosterone levels.  This study found that suppression of insulin resulted in an increase in SHBG production from the liver in both obese and normal weight men.  Of note, the decrease in insulin resulted in a decrease in male Testosterone in both normal weight and obese men.
Nathan Goodyear

Relationship between Low Free Testosterone Levels and Loss of Muscle Mass : Scientific Reports : Nature Publishing Group - 0 views

www.nature.com/...srep01818.html

muscle men male hormone Testosterone free Testosterone low T low Testosterone

shared by Nathan Goodyear on 05 Mar 15 - No Cached
  • Our data confirm that a low FT level is a significant predictor of a risk for loss of appendicular muscle
  • Total lean mass is associated with bioavailable T in postmenopausal women
  • Further studies are needed to determine the role of androgens in preserving muscle mass in women
  • ...11 more annotations...
  • Approximately 1% to 2% of T in the blood exists as FT
  • appendicular muscle loss was significantly associated with low levels of FT
  • These results suggest that a threshold level of FT exists for muscle loss, rather than a dose-response relationship
  • In the previous cross-sectional and longitudinal studies of French and American men, no dose-response relationships were reported between T and muscle mass
  • A minimal serum level of FT may be needed to preserve muscle mass in men, regardless of race/ethnicity.
  • Our result is in line with previous studies that reported a relationship between low FT and low muscle mass in men
  • T stimulates protein synthesis and inhibits protein degradation in muscle cells
  • T also increases satellite cell replication and activation in older men
  • In this study, no significant association between TT levels and muscle loss were observed
  • Although a progressive decrease in TT levels with ageing is observed in middle-aged and elderly American men16, 17, the TT levels do not change during ageing in Japanese men
  • FT levels may be a good marker for the loss of muscle mas
  • Nathan Goodyear on 05 Mar 15
     
    study of Japanese men finds that low free Testosterone was a predictor of decrease in muscle mass.
Nathan Goodyear

Mitochondrial Fission Induces Glycolytic Reprogramming in Cancer-Associated Myofibroblasts, Driving Stromal Lactate Production, and Early Tumor Growth - 0 views

www.ncbi.nlm.nih.gov/...PMC3478457

warburg effect Cancer cancer associated fibroblasts CAFs reverse warburg effect lactate aerobic glycolysis mitochondria oxidative stress ROS H2O2

shared by Nathan Goodyear on 11 Nov 14 - No Cached
  • L-lactate functions as an onco-metabolite, stimulating mitochondrial biogenesis and OXPHOS in adjacent cancer cells, directly providing energy for tumor growth
  • Oxidative stress in stromal fibroblasts then induces their metabolic conversion into cancer-associated fibroblasts. Such oxidative stress drives the onset of autophagy, mitophagy, and aerobic glycolysis in fibroblasts, resulting in the local production of high-energy mitochondrial fuels (such as L-lactate, ketone bodies, and glutamine). These recycled nutrients are then transferred to cancer cells, where they are efficiently burned via oxidative mitochondrial metabolism (OXPHOS)
  • stromal L-lactate serves as a high-energy mitochondrial “fuel” for cancer cells. We have termed this new model of cancer metabolism “Two-Compartment Tumor Metabolism”, where two opposing metabolic compartments co-exist, side-by-side, with stromal glycolysis fueling OXPHOS in cancer cells
  • ...10 more annotations...
  • Two-Compartment Tumor Metabolism
  • Reverse Warburg Effect”, is that catabolic fibroblasts should promote tumor growth, without any increases in angiogenesis
  • when cancer cells use L-lactate as a mitochondrial fuel source, this metabolic phenotype is a predictor of lethal cancer metabolism
  • tumor microenvironment is intimately involved in tumor development and progression
  • mitochondrial dysregulation is likely the “root cause” of several human disease(s), and especially epithelial cancers
  • Both in vitro and in vivo studies have now provided convincing evidence that “activated” stromal fibroblasts, a.k.a., myofibroblasts, may play a critical role in initiating tumor recurrence, via paracrine interactions with adjacent tumor epithelial cells
  • A new hypothesis is that cancer is not a cell autonomous disease, but rather a disease of the tumor microenvironment
  • cancer cells behave as metabolic parasites, by inducing oxidative stress in adjacent normal fibroblasts
  • recent experimental evidence indicates that cancer-associated fibroblasts have a catabolic phenotype, and undergo autophagy and mitophagy, resulting in the onset of glycolytic metabolism, driving L-lactate production, and its release into the tumor microenvironment
  • oncogenic mutations in cancer cells lead to ROS production and the “secretion” of hydrogen peroxide species
  • Nathan Goodyear on 11 Nov 14
     
    A good discussion of what is proposed the Reverse Warburg effect.  A process by which the local environment dictates tumor progression.  The cancer cells release ROS primarily in the form of H2O2 and this leads to Cancer Associated Fibroblasts (CAFs) in the stroma.  The altered stromal environment increases ROS further and promotes ocogenic metabolites through the classic Warburg effect.  This high lactate production from the CAFs then is used by the cancer cells via classic oxidative phosphorylation.  Complex, beautiful and still an the understanding is a work in progress.   This study/article points to the importance of oxidative stress in some cancer development through CAFs.
Nathan Goodyear

Antitumor activity of dichloroacetate on C6 glioma cell: in vitro and in vivo evaluation - 0 views

www.ncbi.nlm.nih.gov/...PMC3601023

cancer DCA

shared by Nathan Goodyear on 12 Nov 14 - No Cached
  • the oral bioavailability of DCA is nearly 100%
  • the oral bioavailability of DCA is almost 100%.
  • DCA can penetrate into the traditional chemotherapy sanctuary sites. Interestingly, it was reported that DCA could penetrate across the BBB,30 exhibiting the potential activity for brain therapy.
  • ...23 more annotations...
  • Clinical studies of DCA have shown reduced lactate levels
  • It has been reported that DCA activates the PDH by inhibition of PDK in a dose-dependent manner, and results in increased delivery of pyruvate into the mitochondria
  • The antitumor activity of DCA on nonsmall cell lung cancer, breast cancer, glioblastomas, and endometrial and prostate cancer cells has been demonstrated
  • It is well known that many chemotherapeutic agents have a low therapeutic index in brain tumors.
  • The most common metabolic hallmark of cancer cells is their propensity to metabolize glucose to lactic acid at a high rate even in the presence of oxygen
  • Pyruvate dehydrogenase kinase (PDK) is a gate-keeping enzyme that regulates the flux of carbohydrates (pyruvate) into the mitochondria
  • In the presence of activated PDK, pyruvate dehydrogenase (PDH), a critical enzyme that converts pyruvate to acetyl-CoA instead of lactate in glycolysis, is inhibited, limiting the entry of pyruvate into the mitochondria.
  • the level of Hsp70 was significantly decreased
  • DCA can penetrate the BBB
  • It has been reported that DCA treatment resulted in an increase in the proportion of tumor cells in the S phase, showing a decrease in proliferation as well as the induction of apoptosis
  • Heat shock proteins (HSPs) are involved in protein folding, aggregation, transport, and/or stabilization by acting as a molecular chaperone, leading to the inhibition of apoptosis by both caspase-dependent and/or independent pathways
  • HSPs are overexpressed in a wide range of human cancers and are implicated in tumor cell proliferation, differentiation, invasion, and metastasis
  • Considering the fact that high expression of HSPs is essential for cancer survival, the inhibition of HSPs is an important strategy of anticancer therapy.
  • In addition, after 5 years of continued treatment with oral DCA at a dose of 25 mg/kg, the serum DCA levels are only slightly increased compared with the levels after the first several doses, also showing its safety for oral administration at this dose.
  • DCA can enter the circulation rapidly after oral administration and then generate the stimulation of PDH activity generally within minutes.
  • Our in vivo results in tumor tissues indicated that DCA significantly induced ROS production and decreased MMP in tumor tissues
  • The numbers of microvessels in the DCA treatment groups were significantly decreased, suggesting the potential antiangiogenic effect of DCA
  • Under hypoxic conditions, hypoxia-inducible factor (HIF-1α) is activated and induces angiogenesis
  • In addition, HIF-1α can also induce the expression of PDK,48 which can inhibit the activity of PDH
  • The inhibition effect of DCA on HIF-1α would decrease vascular endothelial growth factor and inhibit angiogenesis
  • the antiangiogenic effect in the 25 mg/kg treatment group was lower than that in 75 mg/kg or 125 mg/kg treatment groups
  • In conclusion, DCA induces the apoptosis of C6 cells through the activation of the mitochondrial pathway, arresting the cell cycle of C6 cells in S phase and down-regulating Hsp70 expression.
  • DCA significantly induced the ROS production and decreased the MMP in tumor tissues. Our in vivo antitumor activity results also indicated that DCA has an antiangiogenic effect
  • Nathan Goodyear on 12 Nov 14
     
    DCA as proposed therapy in cancer.
Nathan Goodyear

Testosterone for the aging male; current evidence and recommended practice - 0 views

www.ncbi.nlm.nih.gov/...PMC2544367

leptin Testosterone low T low Testosterone male hormone hormones

shared by Nathan Goodyear on 27 Oct 14 - No Cached
  • Total serum testosterone consists of free testosterone (2%–3%), testosterone bound to sex hormone binding globulin (SHBG) (45%) and testosterone bound to other proteins (mainly albumin −50%)
  • Testosterone binds only loosely to albumin and so this testosterone as well as free testosterone is available to tissues and is termed bioavailable testosterone
  • Testosterone bound to SHBG is tightly bound and is biologically inactive
  • ...13 more annotations...
  • Bioavailable and free testosterone are known to correlate better than total testosterone with clinical sequelae of androgenization such as bone mineral density and muscle strength
  • peak levels seen in the morning following sleep, which can be maintained into the seventh decade
  • Samples should always be taken in the morning before 11 am
  • The reliable measurement of serum free testosterone requires equilibrium dialysis. This is not appropriate for clinical use as it is very time consuming and therefore expensive.
  • With increasing age, a greater number of men have total testosterone levels just below the normal range or in the low-normal range. In these patients total testosterone can be an unreliable indicator of hypogonadal status.
  • It is advised that at least two serum testosterone measurements, taken before 11 am on different mornings, are necessary to confirm the diagnosis.
  • Patients with serum total testosterone consistently below 8 nmol/l invariably demonstrate the clinical syndrome of hypogonadism and are likely to benefit from treatment. Patients with serum total testosterone in the range 8–12 nmol/l often have symptoms attributable to hypogonadism and it may be decided to offer either a clinical trial of testosterone treatment or to make further efforts to define serum bioavailable or free testosterone and then reconsider treatment. Patients with serum total testosterone persistently above 12 nmol/l do not have hypogonadism and symptoms are likely to be due to other disease states or ageing per se so testosterone treatment is not indicated.
  • Total testosterone levels fall at an average of 1.6% per year whilst free and bioavailable levels fall by 2%–3% per year.
  • With advancing age there is also a reduction in androgen receptor concentration in some target tissues and this may contribute to the clinical syndrome of LOH
  • Metabolic clearance declines with age
  • Gonadotrophin levels rise during aging (Feldman et al 2002) and testicular secretory responses to recombinant human chorionic gonadotrophin (hCG) are reduced
  • There are changes in the lutenising hormone (LH) production which consist of decreased LH pulse frequency and amplitude, (Veldhuis et al 1992; Pincus et al 1997) although pituitary production of LH in response to pharmacological stimulation with exogenous GnRH analogues is preserved
  • the decreases in testosterone levels with aging seem to reflect changes at all levels of the hypothalamic-pituitary-testicular axis
  • Nathan Goodyear on 27 Oct 14
     
    Leptin inhibits male Testosterone production at the level of the hypothalamus and at the testicle level.
Nathan Goodyear

Gonadotropin treatment restores in vitro interleukin-1β and tumour necrosis factor-α production by stimulated peripheral blood mononuclear cells from patients with idiopathic hypogonadotropic hypogonadism - 0 views

www.ncbi.nlm.nih.gov/...PMC1808705

Testosterone inflammation LPS IL-1beta TNF-alpha low T low Testosterone hypogonadism

shared by Nathan Goodyear on 14 Apr 15 - No Cached
  • Nathan Goodyear on 14 Apr 15
     
    Inverse relationship between Testosterone and LPS, IL-1beta, and TNF-alpha.
Nathan Goodyear

Muscle Hypertrophy 2011 - 0 views

www.unm.edu/...hypertrophy2011UNM.html

resistance training weight lifting muscle exercise weight training

shared by Nathan Goodyear on 20 Mar 15 - No Cached
  • mechanical tension, muscle damage and metabolic stress are the three primary factors that promote hypertrophy from exercise
  • The mechanical tension is directly related to intensity of the exercise, which is the key to stimulating muscle growth
  • Muscle damage, that leads to muscle soreness, from exercise training initiates an inflammatory response, which activates satellite cells growth processes
  • ...6 more annotations...
  • metabolic stress that is a result of the byproducts of anaerobic metabolism (i.e., hydrogen ions, lactate, inorganic phosphates) is now also believed to promote hormonal factors leading to muscle hypertrophy
  • The upper extremities tend to show more growth earlier then the lower body
  • Maximal growth occurs with loads between 80-95% of 1 repetition maximum
  • weightlifters and powerlifters show more favorable hypertrophy of type II (fast twitch) muscle fibers
  • body builders appear to have comparable hypertrophy in both the type I (slow twitch) and type II muscle fibers
  • Multi-joint exercises have been shown to produce larger increases of anabolic hormones than single-joint exercises
  • Nathan Goodyear on 20 Mar 15
     
    Review of the physiology of muscle building.  The authors review the evidence behind the types of muscle building exercises and the physiology responsible for muscle hypertrophy.  The authors point to Schoenfeld's description of mechanical tension, muscle damage, and metabolic stress to build muscle.
Nathan Goodyear

Testosterone physiology in resistance exercise an... [Sports Med. 2010] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...21058750

resistance exercise physiology testosterone men male hormone hormones

shared by Nathan Goodyear on 29 Jul 14 - No Cached
  • testosterone stimulates protein synthesis
  • promotion of muscle hypertrophy by testosterone
  • intracellular androgen receptor (AR)
  • ...8 more annotations...
  • In general, testosterone concentration is elevated directly following heavy resistance exercise in men
  • Findings on the testosterone response in women are equivocal with both increases and no changes observed in response to a bout of heavy resistance exercise
  • Age also significantly affects circulating testosterone concentrations.
  • Aging beyond 35-40 years is associated with a 1-3% decline per year in circulating testosterone concentration in men
  • aging results in a reduced acute testosterone response to resistance exercise in men.
  • In women, circulating testosterone concentration also gradually declines until menopause, after which a drastic reduction is found.
  • acute increases in testosterone can be induced by resistance exercise
  • testosterone is an important modulator of muscle mass in both men and women
  • Nathan Goodyear on 29 Jul 14
     
    Resistance training to increase endogenous Testosterone production: more specific, the exercise must be high rep or as the authors call it--high volume.  To do this, the weight needs to be light.
Nathan Goodyear

Anemia in cancer - 0 views

annonc.oxfordjournals.org/...vii167.long

cancer anemia

shared by Nathan Goodyear on 30 Mar 15 - No Cached
  • Anemia is a frequent finding in cancer patients, occurring in &gt;40% of cases
  • chemotherapy, the incidence of anemia may rise to 90%
  • Anemia exerts a negative influence on the quality of life
  • ...17 more annotations...
  • Anemia has also been identified as an adverse prognostic factor
  • mild (10 g/dl—normal), moderate (8–10 g/dl), severe (6.5–8 g/dl) and life threatening (&lt;6.5 g/dl or unstable patient) anemia
  • anemia in cancer patients is often multifactorial.
  • Cancer itself can directly cause or exacerbate anemia either by suppressing hematopoiesis through bone marrow infiltration or production of cytokines that lead to iron sequestration, or by reduced red blood cell production
  • in inflammatory anemia, iron deficiency should be defined by a low transferrin saturation of &lt;20%, ferritin levels of &lt;100 ng/ml and a low reticulocyte hemoglobin concentration of &lt;32 pg
  • anemia to thrombocytosis, as commonly seen in cancer patients
  • TNF-α inhibits hemoglobin production
  • treatment itself may be a major cause of anemia
  • Other cytokines, such as interleukin-6 (IL-6), IL-1 and interferon-γ, have also been shown to inhibit erythroid precursors in vitro [9], albeit to a lesser extent
  • In inflammation, from whatever cause, IL-6 induces the liver to produce hepcidin. Hepcidin decreases iron absorption from the bowel and blocks iron utilization in the bone marrow
  • Numerous in vitro studies have illustrated the central role of TNF-α in the pathogenesis of anemia
  • nephrotoxic effects of particular cytotoxic agents such as platinum salts can also lead to the persistence of anemia through reduced Epo production by the kidney
  • Currently two options are at the disposal of the clinician for the treatment of anemia in cancer patients: transfusion of packed red blood cells and the use of erythropoiesis-stimulating agents (ESAs)
  • The goal of the treatment is to relieve the symptoms of anemia such as fatigue and dyspnea.
  • Transfusion of 1 unit of packed red blood cells has been estimated to result in an increase in the hemoglobin level of 1 g/dl in a normal-sized adult
  • a higher mortality rate in patients receiving ESA treatment
  • Recent concerns regarding the risk of thromboembolism in patients treated with ESA have been corroborated by the meta-analyses conducted by Tonnelli and Bennett
  • Nathan Goodyear on 30 Mar 15
     
    Great review of anemia in Cancer:  1)  blood loss 2)  increased RBC loss 3)   decreased RBC production Cancer infiltration of marrow can reduce hematopoiesis.  Inflammatory cytokines can reduce hematopoiesis.  Inflammatory cytokines can block Fe absorption.  Chemo and radiation can cause anemia--particularily platinum based therapies.
Nathan Goodyear

Erratum to: Testosterone stimulates glucose uptake and GLUT4 translocation through LKB1/AMPK signaling in 3T3-L1 adipocytes. - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...26820143

Testosterone GLUT4 glucose

shared by Nathan Goodyear on 02 Feb 16 - No Cached
  • Nathan Goodyear on 02 Feb 16
     
    Testosterone increases glucose intake through increased GLUT4 translocation and activity.
Nathan Goodyear

Circulating 2-hydroxy and 16-α hydroxy estrone levels and risk of breast cancer among postmenopausal women - 1 views

www.ncbi.nlm.nih.gov/...PMC2562592

estrogen metabolism menopause post-menopause post menopause estrogen metabolite 2-OH-estrone 16-alpha-OH-estrone 2:16alpha-OH estrone breast cancer risk hormone hormones

shared by Nathan Goodyear on 21 Aug 14 - No Cached
  • 2-OH estrogens bind to the estrogen receptor (ER) with affinity equivalent to or greater than estradiol
  • previous prospective studies have not observed any significant associations with either 2-OH or 16α-OH estrone or the ratio of the two metabolites and breast cancer risk overall.
    • Nathan Goodyear
      Nathan Goodyear on 08 Oct 15
       
      whether that risk is increased or decreased
  • it has been hypothesized that metabolism favoring the 2-OH over the 16α-OH pathway may be inversely associated with breast cancer risk (28).
  • ...24 more annotations...
  • they may act as only weak mitogens (14, 15), or as inhibitors of proliferation
  • No significant associations have been observed between 2-OH estrone and breast cancer risk
  • While 16α-OH estrone binds to the ER with lower affinity than estradiol, it binds covalently (18-20) and once bound, fails to down-regulate the receptor (21). Thus, 16α-OH estrone stimulates cell proliferation in a manner comparable to estradiol in ER+ breast cancer cell lines
  • In this large prospective study of 2-OH and 16α-OH estrone metabolites and breast cancer risk, we did not observe any significant associations overall with either individual metabolite or with the ratio of the two metabolites
  • we observed positive associations with 2-OH estrone and the 2:16α-OH estrone ratio among women with lower BMI and women with ER-/PR-tumors,
  • To date, several epidemiologic studies have examined the association between the 2-OH and 16α-OH estrogen metabolites and breast cancer risk with inconclusive results.
  • circulating estrogen levels have been associated more strongly with ER+/PR+ tumors than with ER-/PR- tumors
  • our results do not support the hypothesis that metabolism favoring the 2-OH estrone pathway is more beneficial to breast cancer risk than that favoring the 16α-OH estrone pathway
  • we observed significant positive associations of both 2-OH estrone and the 2:16α-OH estrone ratio with ER-/PR-tumors
  • Three (30, 32, 33) of four (30-33) studies observed RRs above 1 for the association between 16α-OH estrone and breast cancer risk (range of RRs=1.23-2.47); none of the point estimates was statistically significant though one trend was suggestive
  • based on animal studies, 2-OH estrone and the 2:16α-OH estrone ratio have been hypothesized to be inversely associated with breast cancer risk
  • No significant associations have been observed between 2-OH estrone, 16α-OH estrone, or the 2:16α-OH estrone ratio and breast cancer risk and the direction of the estimates is not consistent across studies.
    • Nathan Goodyear
      Nathan Goodyear on 08 Oct 15
       
      better worded is no consistent, significant associations.   There are some studies that point to the 16 catecholestrogen and increased cancer risk; limited studies show negative effects of 2 catecholestrogens on cancer risk and prospective studies available pretty much dispel the idea that the 2:16 ratio has an risk predictability.
  • we observed a suggestive inverse association with 16α-OH estrone and a significant positive association with the 2:16α-OH estrone ratio among lean women, suggesting possible associations in a low estrogen environment.
  • 16α-OH estrone increases unscheduled DNA synthesis in mouse mammary cells (27) and hence also may be genotoxic
  • Although 2-OH estrogens are capable of redox cycling, the semiquinones and quinones (i.e., the oxidized forms) form stable DNA adducts that are reversible without DNA destruction
  • In our population of PMH nonusers, we observed no associations with ER+/PR+ tumors, but significant positive associations with 2-OH estrone and the 2:16α-OH estrone ratio among women with ER-/PR- tumors
    • Nathan Goodyear
      Nathan Goodyear on 08 Oct 15
       
      one of the few studies to find this association between 2 catecholestrogens and the 2:16 ratio and ER-/PR-tumors
  • Animal and in vitro studies have shown that hydroxy estrogens can induce DNA damage either directly, through the formation of quinones and DNA adducts, or indirectly, through redox cycling and the generation of reactive oxygen species
    • Nathan Goodyear
      Nathan Goodyear on 08 Oct 15
       
      genotoxic via directe DNA adducts and indirectly via ROS; this is in addition to the proliferative effect
  • we observed a significant positive association between the 2:16α-OH estrone ratio and breast cancer risk among lean women
  • No significant associations have been observed with the 2:16α-OH estrone ratio
  • In the Danish study, no associations were observed with either ER+ or ER- tumors among PMH nonusers
  • significant positive associations with 2-OH estrone and the 2:16α-OH estrone ratio were observed among PMH users with ER+, but not ER-, tumors
  • it is possible that the genotoxicity of 2-OH estrone plays a role in hormone receptor negative tumors
  • 4-OH estrogens have a greater estrogenic potential than 2-OH estrogens, given the lower dissociation rate from estrogen receptors compared with estradiol (61), and are potentially more genotoxic since the quinones form unstable adducts, leading to depurination and mutation in vitro and in vivo
  • the balance between the catechol (i.e., 2-OH and 4-OH) and methoxy (i.e., 2-Me and 4-Me) estrogens may impact risk
  • Nathan Goodyear on 21 Aug 14
     
    The risks of estrogen metabolism are not clear cut.  Likely never will be due to the complexity of individual metabolism.  This study found no correlation between 2OH-Estrone and 2OH:16alpha-Estrone and breast cancer risk in ER+/PR+ breast cancer.  Translated: no benefit in breast cancer risk in 2OH-Estrone metabolism or increased 2OH:16alpha estrone metabolism.  There was a positive association between 2OH-Estrone and 2:16alpha-Estrone in women with ER-/PR- tumors and low BMI.
  • anonymous on 28 Oct 15
     
    pakistani sexy girls escort in dubai // russian sexy girsl escort in dubai // sexy girls in dubai // sexy girls escort in dubai //
Nathan Goodyear

Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells - 0 views

www.jci.org/...37948

Cancer THC autophagy medical marijuana glioblastoma

shared by Nathan Goodyear on 12 Nov 18 - No Cached
  • Nathan Goodyear on 12 Nov 18
     
    Describes the mechanism by which THC induces autophagy cell death of glioma cells.
Nathan Goodyear

Hypercalcemia of malignancy and new treatment options - 0 views

www.ncbi.nlm.nih.gov/...PMC4675637

hypercalcemia calcium cancer

shared by Nathan Goodyear on 11 Sep 18 - No Cached
  • Hypercalcemia of malignancy occurs as the result of direct bone metastasis and via humoral mechanisms such as parathyroid hormone-related protein (PTHrP) or 1,25-dihydroxyvitamin D mediated pathways
  • ectopic secretion of parathyroid hormone (PTH) has been implicated
  • Hypercalcemia due to osteolytic bone lesions is common in multiple myeloma, leukemia, and breast cancer
  • ...22 more annotations...
  • Humoral hypercalcemia is predominant in squamous cell, renal cell and ovarian cancers, and lymphomas are associated with 1,25-dihydroxyvitamin D mediated hypercalcemia
  • 20% of cases of hypercalcemia of malignancy and is frequently encountered in multiple myeloma, metastatic breast cancer, and to a lesser extent in leukemia and lymphoma
  • Physiologic bone turnover requires the complementary activity of osteoblasts – mesenchymal stem cell-derived bone-forming cells – and bone-resorbing cells of monocyte and macrophage lineage known as osteoclasts
  • In local osteolytic hypercalcemia, the RANKL/RANK interaction results in excessive osteoclast activation leading to enhanced bone resorption and thus hypercalcemia
  • In addition, osteoclast activation is also mediated by malignancy secreted cytokines, including interleukin-1, initially termed “osteoclast stimulating factor”
  • Macrophage inflammation protein 1-alpha (MIP 1-alpha)
  • hypercalcemia is through extra-renal 1,25-dihydroxyvitamin D (calcitriol) production
  • 1% of cases
  • increased production of 1,25-dihydroxyvitamin D occurs nearly exclusively in Hodgkin and non-Hodgkin lymphoma with case reports of the same in ovarian dysgerminoma
  • 1-α-hydroxylase in the kidney, a process regulated by PTH
  • in 1,25-dihydroxyvitamin D induced hypercalcemia, malignant cells likely recruit and induce adjacent macrophages to express 1-α-hydroxylase, converting endogenous calcidiol into calcitriol.31 Calcitriol then binds to receptors in the intestine leading to heightened enteric calcium reabsorption with resultant hypercalcemia
  • this mechanism of disease is best conceptualized as an absorptive form of hypercalcemia
  • Ectopic production of PTH by malignant cells has been described in a handful of cases involving cancer of the ovary and lung, as well as neuroendocrine tumors and sarcoma
  • primary hyperparathyroidism and malignancy comprising nearly 90% of cases of hypercalcemia
  • an initial panel consisting of PTH, PTHrP, phosphorus, 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D should be obtained
  • Lymphoma, a hypercalcemia due to 1,25-dihydroxyvitamin D mediated pathways, is implied by elevations in 1,25-dihydroxyvitamin D without concomitant elevations in 25-hydroxyvitamin D. In such cases, PTH is low and PTHrP undetectable
  • Treatment of hypercalcemia of malignancy is aimed at lowering the serum calcium concentration by targeting the underlying disease, specifically by inhibiting bone resorption, increasing urinary calcium excretion, and to a lesser extent by decreasing intestinal calcium absorption
  • mildly symptomatic disease
  • marked symptoms
  • hydration with isotonic fluid (if admitted), avoidance of thiazide diuretics, and a low-calcium diet
  • denosumab
  • Denosumab is an RANKL antibody that inhibits osteoclast maturation, activation, and function
  • Nathan Goodyear on 11 Sep 18
     
    hypercalcemia in cancer and treatments.
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