Skip to main content

Home/ Dr. Goodyear/ Group items tagged data

Rss Feed Group items tagged

Filter: All | Bookmarks | Topics Simple Middle
Nathan Goodyear

Intravenous Fluid Use in Athletes - 0 views

www.ncbi.nlm.nih.gov/...PMC3435915

IV nutrition intravenous fluids exercise sports medicine sports athlete athletes

shared by Nathan Goodyear on 13 Jan 15 - No Cached
  • The current data suggest that IV rehydration is faster than oral
  • There may be physiological benefits of decreased heart rate and norepinephrine in athletes rehydrated via IV route
  • Muscle damage during exercise in the heat was assessed by myoglobin and creatine kinase
  • ...4 more annotations...
  • Postexercise blood 1 hour and 24 hours showed no differences in circulating myoglobin or creatine kinase
  • IV administration of fluids can rapidly replace plasma volume
  • The rapid increase in plasma volume is transient, and no measureable difference between IV and oral prehydration exists after 15 minutes of exercise
  • The use of IV fluid may be beneficial for a subset of fluid sensitive athletes
  • Nathan Goodyear on 13 Jan 15
     
    IV nutrition pre-event, intra-event, and post-event for recovery.
Nathan Goodyear

International Journal of Impotence Research - Obesity, low testosterone levels and erec... - 0 views

www.nature.com/...ijir200842a.html

low T low Testosterone men male hormone hormones ED erectile dysfunction Testosterone diabetes metabolic syndrome obesity

shared by Nathan Goodyear on 27 Jan 15 - No Cached
  • Studies have shown that ED may be an early biomarker of general endothelial dysfunction, atherosclerosis and CVD
  • testosterone treatment of hypogonadal young and older men improves sexual function, increases lean mass and decreases fat mass
  • In men with low serum testosterone (for example, <8 or 230 nmol l−1) with obesity, metabolic syndrome and diabetes mellitus, treatment with testosterone is warranted
  • ...12 more annotations...
  • In obese middle-aged men, testosterone treatment reduced visceral adipocity, insulin resistance, serum cholesterol and glucose levels
  • testosterone replacement has a favorable impact on body mass, insulin secretion and sensitivity, lipid profile and blood pressure in hypogonadal men with the metabolic syndrome as well as type 2 diabetes mellitus
  • Testosterone significantly inhibits lipoprotein lipase activity, which reduces triglycerides uptake into adipocytes in the abdominal adipose tissue
  • testosterone treatment decreased endogenous inflammatory cytokines (tumor necrosis factor-α and IL-1β) and lipids (total cholesterol) and increased IL-10 in hypogonadal men
  • Testosterone treatment reduced leptin and adiponectin levels in hypogonadal type 2 diabetic men after 3 months of testosterone replacement
  • available data clearly show a relationship between obesity, low testosterone levels and ED
  • Obesity adversely affects endothelial function and lowers serum testosterone levels through the development of insulin resistance and metabolic syndrome
  • Metabolic disturbances as well as production of cytokines and adipokines by inflamed fat cells may be causal factors in the development of ED
  • The onset of ED and the associated risk of CVD may be delayed through lifestyle modifications that affect obesity, such as diet and exercise
  • Very low testosterone levels contribute to the development of ED in obesity, metabolic syndrome and type 2 diabetes mellitus
  • Obesity is associated with low total testosterone levels that can be explained at least partially by lower sex hormone-binding globulin (SHBG) in obese men
  • epidemiological studies have shown a negative correlation between BMI and total testosterone and to a lesser extent with free and bioavailable (biologically active) testosterone levels
  • Nathan Goodyear on 27 Jan 15
     
    Obesity is associated with low Testosterone and ED in men.
Nathan Goodyear

PLOS ONE: Testosterone, Sex Hormone-Binding Globulin and the Metabolic Syndrome in Men:... - 0 views

journals.plos.org/...article

Testosterone metabolic syndrome total Testosterone free Testosterone SHBG men male hormone hormones

shared by Nathan Goodyear on 03 Mar 15 - No Cached
  • Nathan Goodyear on 03 Mar 15
     
    Meta-analysis finds that men with low total Testosterone, free Testosterone, and SHBG are more at risk for MetS than those with elevated levels.
Nathan Goodyear

Relationship between Low Free Testosterone Levels and Loss of Muscle Mass : Scientific ... - 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

PLOS ONE: Testosterone, Sex Hormone-Binding Globulin and the Metabolic Syndrome in Men:... - 0 views

www.plosone.org/...10.1371%2Fjournal.pone.0100409

metabolic syndrome Total Testosterone Total Testosterone free free Testosterone SHBG BMI obese overweight men male hormone hormones

shared by Nathan Goodyear on 06 Aug 14 - No Cached
  • Nathan Goodyear on 06 Aug 14
     
    Association of low TT, SHBG, and free Testosterone with MetS was found in this study on men.  The association was influenced by BMI i.e. the overweight were found to have a higher association than the normal BMI.
Nathan Goodyear

Androgen therapy and atherosclerotic cardiovascular disease - 0 views

www.ncbi.nlm.nih.gov/...PMC2464747

cardiovascular disease hormone hormones men women male female

shared by Nathan Goodyear on 13 Aug 14 - No Cached
  • In women, it is much clearer that androgen excess is linked to the burden of CVD risk factors
  • insulin resistance is a consequence of androgen effects
  • Women with PCOS have a sustained exposure to high physiologic androgen levels. This condition is associated with endothelial dysfunction, obesity and metabolic abnormalities such as insulin resistance and dyslipidaemia
  • ...4 more annotations...
  • Further evidence of a link between high androgen levels and CVD or CVD risk factors is observed in women with polycystic ovary syndrome (PCOS)
  • For T treatment in aging women, the current data would suggest androgen excess has adverse effects on CVD risk factors, especially in women with diabetes
  • androgen use and abuse is increasing in our society, either for therapeutic or recreational reasons
  • For men, exogenous T treatment appears largely beneficial
  • Nathan Goodyear on 13 Aug 14
     
    I love these review articles that highlight the metabolic differences of hormones in women versus men.  The medical community as a whole doesn't seem to get this at all.  The marketing-based medical community doesn't either.
Nathan Goodyear

https://www.cayugamed.org/docs/Nutrition_Update_for_the_Ultraendurance_Athlete%208.pdf - 0 views

www.cayugamed.org/...Ultraendurance_Athlete%208.pdf

endurance athletes endurance exercise nutrition athletes athlete

shared by Nathan Goodyear on 10 Jan 15 - No Cached
  • Nathan Goodyear on 10 Jan 15
     
    Nutrition for ultra endurance.  To be read.
Nathan Goodyear

An inverse relationship between cortisol and BDNF levels in schizophrenia: data from hu... - 0 views

www.ncbi.nlm.nih.gov/...20451611

BDNF cortisol brain hormone hormones schizophrenia

shared by Nathan Goodyear on 26 Mar 15 - No Cached
  • Nathan Goodyear on 26 Mar 15
     
    Elevated Cortisol found to have inverse association with BDNF.
Nathan Goodyear

Effect of Neoadjuvant Chemotherapy Plus Regional Hyperthermia on Long-term Outcomes Amo... - 0 views

jamanetwork.com/...2672386

hyperthermic therapy hyperthermia cancer chemotherapy

shared by Nathan Goodyear on 30 Aug 18 - No Cached
  • Heat exposure (40 °C to 43 °C) of cancer cells in preclinical studies, and hyperthermia regionally applied to patients in early randomized clinical studies, have shown synergistic activity with ionizing radiation and chemotherapy
  • For the combination of hyperthermia with chemotherapy, the study group at Munich7 was the first to demonstrate the safety and efficacy of regional hyperthermia (RHT) in patients with high-risk sarcoma.
  • Nathan Goodyear on 30 Aug 18
     
    hyperthermia therapy augments chemo therapy.
Nathan Goodyear

Anticancer mechanisms of cannabinoids - 0 views

www.ncbi.nlm.nih.gov/...PMC4791144

THC cannabinoids cancer

shared by Nathan Goodyear on 18 Sep 18 - No Cached
  • modulating key cell signalling pathways involved in the control of cancer cell proliferation and survival
  • cannabinoids inhibit angiogenesis and decrease metastasis in various tumour types in laboratory animals
  • Cannabis sativa L. (marijuana)
  • ...41 more annotations...
  • of the approximately 108 cannabinoids produced by C. sativa, Δ9-tetrahydrocannabinol (thc) is the most relevant because of its high potency and abundance in plant preparations
  • Tetrahydrocannabinol exerts a wide variety of biologic effects by mimicking endogenous substances—the endocannabinoids anandamide3 and 2-arachidonoylglycerol4,5—that engage specific cell-surface cannabinoid receptors
  • the cb2 receptor was initially described to be present in the immune system6, but was more recently shown to also be expressed in cells from other origins
  • transient receptor potential cation channel subfamily V, member 1
  • orphan G protein–coupled receptor 55
  • Most of the effects produced by cannabinoids in the nervous system and in non-neural tissues rely on cb1 receptor activation
  • two major cannabinoid-specific receptors—cb1 and cb2
  • cardiovascular tone, energy metabolism, immunity, and reproduction
  • cannabinoids are well known to exert palliative effects in cancer patients
  • best-established use is the inhibition of chemotherapy-induced nausea and vomiting
  • thc and other cannabinoids exhibit antitumour effects in a wide array of animal models of cancer
  • cannabinoid receptors and their endogenous ligands are both generally upregulated in tumour tissue compared with non-tumour tissue
  • cb2 promotes her2 (human epidermal growth factor receptor 2) pro-oncogenic signalling in breast cancer
  • pharmacologic activation of cannabinoid receptors decreases tumour growth
  • endocannabinoid signalling can also have a tumour-suppressive role
  • pharmacologic stimulation of cb receptors is, in most cases, antitumourigenic. Nonetheless, a few reports have proposed a tumour-promoting effect of cannabinoids
  • most prevalent effect is the induction of cancer cell death by apoptosis and the inhibition of cancer cell proliferation
  • impair tumour angiogenesis and block invasion and metastasis
  • thc and other cannabinoids induce the apoptotic death of glioma cells by cb1- and cb2-dependent stimulation
  • Autophagy is primarily a cytoprotective mechanism, although its activation can also lead to cell death
  • autophagy is important for cannabinoid antineoplastic activity
  • autophagy is upstream of apoptosis in the mechanism of cannabinoid-induced cell death
  • the effect of cannabinoids in hormone- dependent tumours might rely, at least in part, on the ability to interfere with the activation of growth factor receptors
  • glioma cells), pharmacologic blockade of either cb1 or cb2 prevents cannabinoid-induced cell death with similar efficacy
  • other types of cancer cells (pancreatic48, breast24, or hepatic43 carcinoma cells, for example), antagonists of cb2 but not of cb1 inhibit cannabinoid antitumour actions
  • thc promotes cancer cell death in a cb1- or cb2-dependent manner (or both) at lower concentrations
  • cannabidiol (cbd), a phytocannabinoid with a low affinity for cannabinoid receptors15, and other marijuana-derived cannabinoids57 have also been proposed to promote the apoptotic death of cancer cells acting independently of the cb1 and cb2 receptors
  • In cancer cells, cannabinoids block the activation of the vascular endothelial growth factor (vegf) pathway, an inducer of angiogenesi
  • In vascular endothelial cells, cannabinoid receptor activation inhibits proliferation and migration, and induces apoptosis
  • cb1 or cb2 receptor agonists (or both) reduce the formation of distant tumour masses in animal models of both induced and spontaneous metastasis, and inhibit adhesion, migration, and invasiveness of glioma64, breast65,66, lung67,68, and cervical68 cancer cells in culture
  • the ceramide/p8–regulated pathway plays a general role in the antitumour activity of cannabinoids targeting cb1 and cb2
  • cbd, by acting independently of the cb1 and cb2 receptors, produces a remarkable anti-tumour effect—including reduction of invasiveness and metastasis
  • cannabinoids can also enhance immune system–mediated tumour surveillance in some contexts
  • ability of thc to reduce inflammation75,76, an effect that might prevent certain types of cancer
  • recent observations suggest that the combined administration of cannabinoids with other anticancer drugs acts synergistically to reduce tumour growth
  • combined administration of gemcitabine (the benchmark agent for the treatment of pancreatic cancer) and various cannabinoid agonists synergistically reduced the viability of pancreatic cancer cells
  • Other reports indicated that anandamide and HU-210 might also enhance the anticancer activity of paclitaxel89 and 5-fluorouracil90 respectively
  • Combined administration of thc and cbd enhances the anticancer activity of thc and reduces the dose of thc needed to induce its tumour growth-inhibiting activity
  • Preclinical animal models have yielded data indicating that systemic (oral or intraperitoneal) administration of cannabinoids effectively decreases tumour growth
  • Combinations of cannabinoids with classical chemotherapeutic drugs such as the alkylating agent temozolomide (the benchmark agent for the management of glioblastoma80,84) have been shown to produce a strong anticancer action in animal models
  • pharmacologic inhibition of egfr, erk83, or akt enhances the cell-death-promoting action of thc in glioma cultures (unpublished observations by the authors), which suggests that targeting egfr and the akt and erk pathways could enhance the antitumour effect of cannabinoids
  • Nathan Goodyear on 18 Sep 18
     
    Good review of the anticancer effects of cananbinoids.
Nathan Goodyear

A Combined Preclinical Therapy of Cannabinoids and Temozolomide against Glioma | Molecu... - 0 views

mct.aacrjournals.org/...90.long

cancer THC medical marijuana glioblastoma CBD

shared by Nathan Goodyear on 18 Sep 18 - No Cached
  • Δ9-Tetrahydrocannabinol (THC; Supplementary Fig. 1), the main active component of the hemp plant Cannabis sativa
  • CB1, abundantly expressed in the brain and at many peripheral sites
  • CB2, expressed in the immune system and also present in some neuron subpopulations and glioma cells
  • ...3 more annotations...
  • antitumoral agents
  • Aside from THC, C. sativa produces approximately 70 other cannabinoids, although, unlike THC, many of them exhibit little affinity for CB receptors (10, 20). Of interest, at least one of these components, namely, cannabinol (CBD; Supplementary Fig. 1), has been shown to reduce the growth of different types of tumor xenografts including gliomas
  • the combined administration of THC and CBD is being therapeutically explored (10, 20, 26), although its effects on the proliferation and survival of cancer cells have only been analyzed in vitro
  • Nathan Goodyear on 18 Sep 18
     
    THC found to augment chemotherapy in the glioblastoma cell culture study.
Nathan Goodyear

The current state and future perspectives of cannabinoids in cancer biology - 0 views

www.ncbi.nlm.nih.gov/...PMC5852356

Cancer CBD THC cannabinoids

shared by Nathan Goodyear on 19 Sep 18 - No Cached
hoangkimchi liked it
  • The activation of each of them leads to an inhibition of adenylyl cyclase via G proteins (Gi/o), which in turn activates many metabolic pathways such as mitogen‐activated protein kinase pathway (MAPK), phosphoinositide 3‐kinase pathway (PI3K), cyclooxygenase‐2 pathway (COX‐2), accumulation of ceramide, modulation of protein kinase B (Akt), and ion channels
  • phytocannabinoids, endocannabinoids, and synthetic cannabinoids
  • Action of THC in human organism relies on mimicking endogenous agonists of CB receptors—endocannabinoids
  • ...8 more annotations...
  • The upregulated expression of CB receptors and the elevated levels of endocannabinoids have been observed in a variety of cancer cells (skin, prostate, and colon cancer, hepatocellular carcinoma, endometrial sarcoma, glioblastoma multiforme, meningioma and pituitary adenoma, Hodgkin lymphoma, chemically induced hepatocarcinoma, mantel cell lymphoma)
  • concentration of endocannabinoids, expression level of their receptors, and the enzymes involved in their metabolism frequently are associated with an aggressiveness of cancer
  • CB2 receptor contributes to human epidermal growth factor receptor (HER2) pro‐oncogenic signaling and an overexpression of CB2 increases susceptibility for leukemia development after leukemia viral infection
  • endocannabinoid‐degrading enzymes are upregulated in cancer cell lines and in human tumors
  • Many cannabinoids, ranging from phytocannabinoids (THC, CBD), endocannabinoids (2‐arachidonoylglycerol, anandamide), to synthetic cannabinoids (JWH‐133, WIN‐55,212‐2), have shown ability to inhibit proliferation, metastasis, and angiogenesis in a variety of models of cancer
  • Despite some inconsistent data, the main effect of cannabinoids in a tumor is the inhibition of cancer cells’ proliferation and induction of cancer cell death by apoptosis
  • CB1 and CB2 receptor agonists stimulate apoptotic cell death in glioma cells by induction of de novo synthesis of ceramide, sphingolipid with proapoptotic activity
  • process of autophagy is upstream of apoptosis in mechanism of cell death induced by cannabinoids
Nathan Goodyear

Vitamin D supplementation to prevent acute respiratory tract infections: systematic rev... - 0 views

www.bmj.com/bmj.i6583

vitamin d respiratory tract infections

shared by Nathan Goodyear on 20 Sep 17 - No Cached
  • Nathan Goodyear on 20 Sep 17
     
    vitamin D supplementation found to be beneficial in reducing the risk of acute respiratory tract infections.  This study found more benefit in those with D levels < 25 nmol/L
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 &amp; 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&nbsp;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&nbsp;al, 2009; Scheperset&nbsp;al, 2012; Zhuet&nbsp;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 ˜&nbsp;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 &amp; Gouaux, 2011; Lynagh &amp; 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 (&gt;&nbsp;10&nbsp;μM for 12&nbsp;h or longer or &gt;&nbsp;5&nbsp;μM for 48&nbsp;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&nbsp;al, 2013; Ziskinet&nbsp;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&nbsp;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&nbsp;al, 1990) and that this drug does not cross the blood–brain barrier (Kokozet&nbsp;al, 1999). Similarly, only dogs with mutantABCB1 (MDR1) alleles leading to a broken blood–brain barrier show Ivermectin neurotoxicity (Mealeyet&nbsp;al, 2001; Orzechowskiet&nbsp;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

18FDG-PET/CT for predicting the outcome in ER+/HER2- breast cancer patients: comparison... - 0 views

breast-cancer-research.biomedcentral.com/...s13058-016-0793-2

PET scan cancer breast cancer

shared by Nathan Goodyear on 19 Mar 18 - No Cached
  • our study confirms that baseline PET parameters measured before neoadjuvant treatment have prognostic values in ER+/HER2- locally advanced breast cancer patients
  • It has been suggested that high baseline 18F-fluorodeoxyglucose (18FDG) uptake assessed by high standardized uptake value (SUV) could be associated with poor prognostic factors such as the high histological grade [2] as well as worse survival
  • several teams observed that the change in SUV values early during neoadjuvant treatment could be a good indicator of pathological response and potentially outcome
  • ...5 more annotations...
  • others studies suggested that baseline 18FDG uptake, which would avoid performing a second examination, could also be of interest to predict patient outcome, especially in ER+/HER2- BC
  • ER+/HER2- BC has less intense 18FDG uptake than some other phenotypes such as TN carcinoma
  • Patients with high baseline 18FDG tumor uptake are at higher risk of early recurrence
  • The 3-year EFS was 78.4% in patients with baseline tumor SUVmax &gt; 8.3 (vs. 94.0% in those with SUVmax ≤ 8.3)
  • event-free survival (EFS)
  • Nathan Goodyear on 19 Mar 18
     
    Study finds benefit of PET scan in prognosis in ER+/HER2- breast cancers.
Nathan Goodyear

Evaluation of FLT-PET-CT as an imaging biomarker of proliferation in primary breast can... - 0 views

www.nature.com/...bjc2014207

PET scan PET_CT scan cancer breast

shared by Nathan Goodyear on 19 Mar 18 - No Cached
  • We have demonstrated that the majority of patients have a sizeable reduction in SUVmax from a single cycle of NAC with a mean change of −32.3%
  • This study, however, failed to show any predictive markers of response after one cycle of chemotherapy
  • These data therefore suggest that the main utility of FLT-PET as an imaging biomarker in early breast cancer is pre-chemotherapy, as a marker of proliferation, rather than in predicting pathological response after chemotherapy
  • ...2 more annotations...
  • In terms of the histological proliferation biomarker Ki-67, we have shown a good correlation with FLT-PET pre-chemotherapy. The best predictive marker of response in terms of pCR was baseline Ki-67
  • Our study has shown that baseline Ki-67 and FLT SUVmax is well correlated in keeping with FLT-PETs status as a proliferation biomarker, although Ki-67 had a better predictive ability in terms of pathological outcome
  • Nathan Goodyear on 19 Mar 18
     
    PET CT scan shown to be useful as a proliferation biomarker pre-chemo in breast cancer.
Nathan Goodyear

Anticancer Effects of Niclosamide in Human Glioblastoma | Clinical Cancer Research - 0 views

clincancerres.aacrjournals.org/...4124.long

Niclosamide cancer Glioblastoma glioblastoma multiforme NOTCH mTOR Wnt

shared by Nathan Goodyear on 16 Apr 18 - No Cached
  • glioblastoma remains a fatal disease with a median overall survival time of only 15 months
  • inter- and intrapatient tumor heterogeneity
  • cellular and genetic diversity that characterizes glioblastoma
  • ...5 more annotations...
  • This broad effect could be a result of niclosamide's pleiotropic activity, similarly affecting signaling pathways that are known to be overly active in human malignant cells (i.e., mTOR, NOTCH, WNT/CTNNB1; refs. 44–46)
  • It is a salicylanilide that was introduced as a molluscide in 1959
  • Studies in animals suggested no mutagenic, oncogenic, or embryotoxic activity and no cumulative effects
  • its rate of absorption from the intestinal tract was estimated at only 33%
  • the potential mechanism of synergy between temozolomide and niclosamide as a “natural inducer” of NFKBIA
  • Nathan Goodyear on 16 Apr 18
     
    Niclosamide pilot animal study useful in the treatment of Glioblastoma.  Found to inhibit NOTCH, mTOR, and WNT and cancer signaling. Also found to reduce the malignant potential through cytostatic, cytotoxic and antimigratory effects of niclosamide on GBM
Nathan Goodyear

Exposure to the Functional Bacterial Amyloid Protein Curli Enhances Alpha-Synuclein Agg... - 0 views

www.nature.com/srep34477

neurodegenerative disease amyloid alzheimer's disease Parkinson's disease gut gut flora gut microbiome gut microbiota gut-brain

shared by Nathan Goodyear on 06 Oct 16 - No Cached
  • Our work suggests that protein misfolding and immune activation in neurodegenerative disorders are triggered through cross-seeding by exposure to exogenous microbial amyloids in the nose, mouth and gut.
  • Streptococcus mutans, Staphlococcus aureus, Salmonella enterica, Mycobacterium tuberculosis and others
  • Gene homologs encoding curli were recently determined also in four phyla: Bacteroidetes, Proteobacteria, Firmicutes, and Thermodesulfobacteria
  • ...8 more annotations...
  • changes in the gut microbiota induced by antibiotics alter neuroinflammation and amyloid deposition in a mouse model of AD
  • Our data suggest that amyloid proteins in the microbiota are involved in the origination and maintenance of neurodegenerative disease.
  • exposure to bacteria producing a functional extracellular amyloid protein enhances aggregation of AS in brain neurons in aged rats and in muscle cells in nematodes
  • AS aggregates seed aggregation of tau
  • involvement of the vagus nerve in PD
  • microgliosis, astrogliosis and enhanced expression of IL-6, TLR2 and TNF in the brain following curli exposure suggest the occurrence of an enhanced local sterile inflammatory response to AS in the brain.
  • the immune system in both AD and PD have now been extensively established
  • TLR2 activation through exposure to bacterial amyloid is pathogenic
  • Nathan Goodyear on 06 Oct 16
     
    Gut bacteria may play crucial role in systemic inflammation that leads to Alzheimer's and Parkinson's disease.  These amyloid production bacteria trigger systemic inflammation that leads to microglia activation and amyloid in the brain.   More establishment of the gut-brain connection.  
Nathan Goodyear

From the Cover: Pharmacologic doses of ascorbate act as a prooxidant and decrease growt... - 0 views

www.ncbi.nlm.nih.gov/...PMC2516281

cancer IV intravenous vitamin C IV vitamin C

shared by Nathan Goodyear on 18 Sep 13 - No Cached
  • An extensive panel of 43 tumor and 5 normal cell lines were exposed to ascorbate in vitro for ≤2 h to mimic clinical pharmacokinetics
  • effective concentration that decreased survival 50% (EC50) was determined. EC50 was &lt;10 mM for 75% of tumor cells tested, whereas cytotoxicity was not evident in normal cells with &gt;20 mM ascorbate
  • The addition of catalase to the medium ameliorated death of ovarian carcinoma (Ovcar5), pancreatic carcinoma (Pan02), and glioblastoma (9L) cells exposed to 10 mM ascorbate (1 h), indicating cytotoxicity was mediated by H2O2
  • ...8 more annotations...
  • A treatment dose of 4 g ascorbate/kg body weight either once or twice daily did not produce any discernible adverse effects
  • Xenograft experiments showed that parenteral ascorbate as the only treatment significantly decreased both tumor growth and weight by 41–53%
  • Peak plasma concentrations of ascorbate approached 30 mM
  • Pharmacologic concentrations of ascorbate decreased tumor volumes 41–53% in diverse cancer types known for both their aggressive growth and limited treatment options.
  • Our findings showed that pharmacologic ascorbic acid concentrations were cytotoxic to many types of cancer cells in vitro (Fig. 1A) and significantly impeded tumor progression in vivo without toxicity to normal tissues
  • The amelioration of ascorbate cytotoxicity in vitro by the addition of catalase was consistent among sensitive cancer cells (Fig. 1B) and points unambiguously to H2O2 generation in the extracellular medium
  • the current in vivo data support that pharmacologic ascorbate concentrations, which can readily be achieved in humans (Fig. 3E), diminished growth of several aggressive cancer types in mice (Fig. 2) without causing apparent adverse effects.
  • These intratumoral H2O2 concentrations of &gt;125 μM persisted for &gt;3 h after ascorbate administration
  • Nathan Goodyear on 18 Sep 13
     
    Tumor xenograft model in mice finds reduction in growth rates of ovarian cancer, pancreatic cancer, and glioblastoma with daily IV vitamin C.
Nathan Goodyear

Frontiers | Branched-Chain Amino Acid Ingestion Stimulates Muscle Myofibrillar Protein ... - 1 views

journal.frontiersin.org/...full

BCAA amino acids resistance training exercise recovery exercise muscle

shared by Nathan Goodyear on 18 Jul 17 - No Cached
  • BCAAs exhibit the capacity to stimulate myofibrillar-MPS, however a full complement of EAA could be necessary to stimulate a maximal response of myofibrillar-MPS following resistance exercise
  • This information potentially has important nutritional implications for selecting amino acid supplements to facilitate skeletal muscle hypertrophy in response to resistance exercise training and the maintenance of muscle mass during aging, unloading, or disease
  • results from the present study suggest that ingesting BCAAs alone, without the other EAA, provides limited substrate for protein synthesis in exercised muscles
  • ...3 more annotations...
  • the overall response of MPS is not maximized. Instead, the limited availability of EAA likely explains the qualitative difference in magnitude of the MPS response to ingestion of BCAAs alone and ingestion of similar amounts of BCAAs as part of intact whey protein
  • decreased EAA concentrations following leucine ingestion
  • these data support the notion that EAA availability is the rate-limiting factor for stimulating a maximal MPS response to resistance exercise with BCAA ingestion
  • Nathan Goodyear on 18 Jul 17
     
    Complete amino acid supplementation exceeds muscle building capacity (myofibrillar-MPS) over BCAA alone.
« First ‹ Previous 181 - 200 of 219 Next ›
Showing 20▼ items per page