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Sample records for hormone receptor-mediated uptake

  1. The liver taxis of receptor mediated lactosaminated human growth hormone

    International Nuclear Information System (INIS)

    Chen Zelian; Shi Lin; Li Tongling; Pang Qijie; He Juying; Guan Changtian

    2002-01-01

    Radiography imaging is used to assess liver taxis mechanism of anti-dwarfism drug lactosaminated human growth hormone (L-rhGH). Both L-rhGH and rhGH labelled with 131 I are used to study their biodistribution in animals (including rabbits, cocks and rats). The results show that L-rhGH is of specific hepatic targeting property, and the maximum hepatic concentration rate is 76.8%, which is two times of rhGH. Its hepatic binding is receptor mediated

  2. Suppression of Thyroid Hormone Receptor-Mediated Transcription ...

    African Journals Online (AJOL)

    TH)-induced TR-mediated transcription. We further examined the effects of methamidophos on TR-thyroid hormone response element (TRE) binding using the liquid chemiluminescent DNA pull-down assay (LCDPA), and found no dissociation of ...

  3. Follicle-stimulating hormone receptor-mediated uptake of 45Ca2+ by proteoliposomes and cultured rat sertoli cells: Evidence for involvement of voltage-activated and voltage-independent calcium channels

    International Nuclear Information System (INIS)

    Grasso, P.; Reichert, L.E. Jr.

    1989-01-01

    We have previously reported incorporation into liposomes of Triton X-100-solubilized FSH receptor-G-protein complexes derived from purified bovine calf testis membranes. In the present study we have used this model system to show that FSH induces flux of 45Ca2+ into such proteoliposomes in a hormone-specific concentration-dependent manner. FSH, inactivated by boiling, had no stimulatory effect on 45Ca2+ flux, nor did isolated alpha- or beta-subunits of FSH. Addition of GTP (or its analogs 5'-guanylylimidodiphosphate and guanosine-5'-O-[3-thiotriphosphate]) or sodium fluoride (in the presence or absence of GTP or its analogs) failed to induce 45Ca2+ flux into proteoliposomes, suggesting that the uptake of 45Ca2+ was receptor, and not G-protein, related. Voltage-independent (ruthenium red and gadolinium chloride) and voltage-activated (methyoxyverapamil and nifedipine) calcium channel-blocking agents reduced FSH-stimulated 45Ca2+ flux into proteoliposomes to control levels. FSH also induced uptake of 45Ca2+ by cultured rat Sertoli cells. Ruthenium red and gadolinium chloride had no effect on basal levels of 45Ca2+ uptake or estradiol secretion by cultured rat Sertoli cells, nor did methoxyverapamil or nifedipine. All four calcium channel blockers, however, were able to reduce FSH-induced 45Ca2+ uptake to basal levels and FSH-stimulated conversion of androstenedione to estradiol by up to 50%, indicating an involvement of Ca2+ in FSH-stimulated steroidogenesis. Our results suggest that the well documented changes in intracellular calcium levels consequent to FSH binding may be due, at least in part, to an influx of calcium through FSH receptor-regulated calcium channels

  4. Characterization of GABA/sub A/ receptor-mediated 36chloride uptake in rat brain synaptoneurosomes

    International Nuclear Information System (INIS)

    Luu, M.D.; Morrow, A.L.; Paul, S.M.; Schwartz, R.D.

    1987-01-01

    γ-Aminobutyric acid (GABA) receptor-mediated 36 chloride ( 36 Cl - ) uptake was measured in synaptoneurosomes from rat brain. GABA and GABA agonists stimulated 36 Cl - uptake in a concentration-dependent manner with the following order of potency: Muscimol>GABA>piperidine-4-sulfonic acid (P4S)>4,5,6,7-tetrahydroisoxazolo-[5,4-c]pyridin-3-ol (THIP)=3-aminopropanesulfonic acid (3APS)>>taurine. Both P4S and 3APS behaved as partial agonists, while the GABA/sub B/ agonist, baclofen, was ineffective. The response to muscimol was inhibited by bicuculline and picrotoxin in a mixed competitive/non-competitive manner. Other inhibitors of GABA receptor-opened channels or non-neuronal anion channels such as penicillin, picrate, furosemide and disulfonic acid stilbenes also inhibited the response to muscimol. A regional variation in muscimol-stimulated 36 Cl - uptake was observed; the largest responses were observed in the cerebral cortex, cerebellum and hippocampus, moderate responses were obtained in the striatum and hypothalamus and the smallest response was observed in the pons-medulla. GABA receptor-mediated 36 Cl - uptake was also dependent on the anion present in the media. The muscinol response varied in media containing the following anions: Br - >Cl - ≥NO 3 - >I - ≥SCN - >>C 3 H 5 OO - ≥ClO 4 - >F - , consistent with the relative anion permeability through GABA receptor-gated anion channels and the enhancement of convulsant binding to the GABA receptor-gated Cl - channel. 43 references, 4 figures, 3 tables

  5. Follicle-stimulating hormone receptor-mediated uptake of 45Ca2+ by cultured rat Sertoli cells does not require activation of cholera toxin- or pertussis toxin-sensitive guanine nucleotide binding proteins or adenylate cyclase

    International Nuclear Information System (INIS)

    Grasso, P.; Reichert, L.E. Jr.

    1990-01-01

    We have previously reported that FSH stimulates flux of 45Ca2+ into cultured Sertoli cells from immature rats via voltage-sensitive and voltage-independent calcium channels. In the present study, we show that this effect of FSH does not require cholera toxin (CT)- or pertussis toxin (PT)-sensitive guanine nucleotide binding (G) protein or activation of adenylate cyclase (AC). Significant stimulation of 45Ca2+ influx was observed within 1 min, and maximal response (3.2-fold over basal levels) was achieved within 2 min after exposure to FSH. FSH-stimulated elevations in cellular cAMP paralleled increases in 45Ca2+ uptake, suggesting a possible coupling of AC activation to 45Ca2+ influx. (Bu)2cAMP, however, was not able to enhance 45Ca2+ uptake over basal levels at a final concentration of 1000 microM, although a concentration-related increase in androstenedione conversion to estradiol was evident. Exposure of Sertoli cells to CT (10 ng/ml) consistently stimulated basal levels of androstenedione conversion to estradiol but had no effect on basal levels of 45Ca2+ uptake. Similarly, CT had no effect on FSH-induced 45Ca2+ uptake, but potentiated FSH-stimulated estradiol synthesis. PT (10 ng/ml) augmented basal and FSH-stimulated estradiol secretion without affecting 45Ca2+ influx. The adenosine analog N6-phenylisopropyladenosine, which binds to Gi-coupled adenosine receptors on Sertoli cells, inhibited FSH-stimulated androgen conversion to estradiol in a dose-related (1-1000 nM) manner, but FSH-stimulated 45Ca2+ influx remained unchanged. Our results show that in contrast to FSH-stimulated estradiol synthesis, the flux of 45Ca2+ into Sertoli cells in response to FSH is not mediated either directly or indirectly by CT- or PT-sensitive G protein, nor does it require activation of AC. Our data further suggest that the FSH receptor itself may function as a calcium channel

  6. Follicle-stimulating hormone receptor-mediated uptake of sup 45 Ca sup 2+ by cultured rat Sertoli cells does not require activation of cholera toxin- or pertussis toxin-sensitive guanine nucleotide binding proteins or adenylate cyclase

    Energy Technology Data Exchange (ETDEWEB)

    Grasso, P.; Reichert, L.E. Jr. (Albany Medical College, NY (USA))

    1990-08-01

    We have previously reported that FSH stimulates flux of 45Ca2+ into cultured Sertoli cells from immature rats via voltage-sensitive and voltage-independent calcium channels. In the present study, we show that this effect of FSH does not require cholera toxin (CT)- or pertussis toxin (PT)-sensitive guanine nucleotide binding (G) protein or activation of adenylate cyclase (AC). Significant stimulation of 45Ca2+ influx was observed within 1 min, and maximal response (3.2-fold over basal levels) was achieved within 2 min after exposure to FSH. FSH-stimulated elevations in cellular cAMP paralleled increases in 45Ca2+ uptake, suggesting a possible coupling of AC activation to 45Ca2+ influx. (Bu)2cAMP, however, was not able to enhance 45Ca2+ uptake over basal levels at a final concentration of 1000 microM, although a concentration-related increase in androstenedione conversion to estradiol was evident. Exposure of Sertoli cells to CT (10 ng/ml) consistently stimulated basal levels of androstenedione conversion to estradiol but had no effect on basal levels of 45Ca2+ uptake. Similarly, CT had no effect on FSH-induced 45Ca2+ uptake, but potentiated FSH-stimulated estradiol synthesis. PT (10 ng/ml) augmented basal and FSH-stimulated estradiol secretion without affecting 45Ca2+ influx. The adenosine analog N6-phenylisopropyladenosine, which binds to Gi-coupled adenosine receptors on Sertoli cells, inhibited FSH-stimulated androgen conversion to estradiol in a dose-related (1-1000 nM) manner, but FSH-stimulated 45Ca2+ influx remained unchanged. Our results show that in contrast to FSH-stimulated estradiol synthesis, the flux of 45Ca2+ into Sertoli cells in response to FSH is not mediated either directly or indirectly by CT- or PT-sensitive G protein, nor does it require activation of AC. Our data further suggest that the FSH receptor itself may function as a calcium channel.

  7. Receptor-mediated uptake of low density lipoprotein stimulates bile acid synthesis by cultured rat hepatocytes

    International Nuclear Information System (INIS)

    Junker, L.H.; Davis, R.A.

    1989-01-01

    The cellular mechanisms responsible for the lipoprotein-mediated stimulation of bile acid synthesis in cultured rat hepatocytes were investigated. Adding 280 micrograms/ml of cholesterol in the form of human or rat low density lipoprotein (LDL) to the culture medium increased bile acid synthesis by 1.8- and 1.6-fold, respectively. As a result of the uptake of LDL, the synthesis of [14C]cholesterol from [2-14C]acetate was decreased and cellular cholesteryl ester mass was increased. Further studies demonstrated that rat apoE-free LDL and apoE-rich high density lipoprotein (HDL) both stimulated bile acid synthesis 1.5-fold, as well as inhibited the formation of [14C]cholesterol from [2-14C]acetate. Reductive methylation of LDL blocked the inhibition of cholesterol synthesis, as well as the stimulation of bile acid synthesis, suggesting that these processes require receptor-mediated uptake. To identify the receptors responsible, competitive binding studies using 125I-labeled apoE-free LDL and 125I-labeled apoE-rich HDL were performed. Both apoE-free LDL and apoE-rich HDL displayed an equal ability to compete for binding of the other, suggesting that a receptor or a group of receptors that recognizes both apolipoproteins is involved. Additional studies show that hepatocytes from cholestyramine-treated rats displayed 2.2- and 3.4-fold increases in the binding of apoE-free LDL and apoE-rich HDL, respectively. These data show for the first time that receptor-mediated uptake of LDL by the liver is intimately linked to processes activating bile acid synthesis

  8. Ultradian hormone stimulation induces glucocorticoid receptor-mediated pulses of gene transcription.

    Science.gov (United States)

    Stavreva, Diana A; Wiench, Malgorzata; John, Sam; Conway-Campbell, Becky L; McKenna, Mervyn A; Pooley, John R; Johnson, Thomas A; Voss, Ty C; Lightman, Stafford L; Hager, Gordon L

    2009-09-01

    Studies on glucocorticoid receptor (GR) action typically assess gene responses by long-term stimulation with synthetic hormones. As corticosteroids are released from adrenal glands in a circadian and high-frequency (ultradian) mode, such treatments may not provide an accurate assessment of physiological hormone action. Here we demonstrate that ultradian hormone stimulation induces cyclic GR-mediated transcriptional regulation, or gene pulsing, both in cultured cells and in animal models. Equilibrium receptor-occupancy of regulatory elements precisely tracks the ligand pulses. Nascent RNA transcripts from GR-regulated genes are released in distinct quanta, demonstrating a profound difference between the transcriptional programs induced by ultradian and constant stimulation. Gene pulsing is driven by rapid GR exchange with response elements and by GR recycling through the chaperone machinery, which promotes GR activation and reactivation in response to the ultradian hormone release, thus coupling promoter activity to the naturally occurring fluctuations in hormone levels. The GR signalling pathway has been optimized for a prompt and timely response to fluctuations in hormone levels, indicating that biologically accurate regulation of gene targets by GR requires an ultradian mode of hormone stimulation.

  9. Identification of a novel modulator of thyroid hormone receptor-mediated action.

    Directory of Open Access Journals (Sweden)

    Bernhard G Baumgartner

    Full Text Available BACKGROUND: Diabetes is characterized by reduced thyroid function and altered myogenesis after muscle injury. Here we identify a novel component of thyroid hormone action that is repressed in diabetic rat muscle. METHODOLOGY/PRINCIPAL FINDINGS: We have identified a gene, named DOR, abundantly expressed in insulin-sensitive tissues such as skeletal muscle and heart, whose expression is highly repressed in muscle from obese diabetic rats. DOR expression is up-regulated during muscle differentiation and its loss-of-function has a negative impact on gene expression programmes linked to myogenesis or driven by thyroid hormones. In agreement with this, DOR enhances the transcriptional activity of the thyroid hormone receptor TR(alpha1. This function is driven by the N-terminal part of the protein. Moreover, DOR physically interacts with TR( alpha1 and to T(3-responsive promoters, as shown by ChIP assays. T(3 stimulation also promotes the mobilization of DOR from its localization in nuclear PML bodies, thereby indicating that its nuclear localization and cellular function may be related. CONCLUSIONS/SIGNIFICANCE: Our data indicate that DOR modulates thyroid hormone function and controls myogenesis. DOR expression is down-regulated in skeletal muscle in diabetes. This finding may be of relevance for the alterations in muscle function associated with this disease.

  10. Receptor-mediated endocytosis of polypeptide hormones is a regulated process: inhibition of [125I]iodoinsulin internalization in hypoinsulinemic diabetes of rat and man

    International Nuclear Information System (INIS)

    Carpentier, J.L.; Robert, A.; Grunberger, G.; van Obberghen, E.; Freychet, P.; Orci, L.; Gorden, P.

    1986-01-01

    Much data suggest that receptor-mediated endocytosis is regulated in states of hormone excess. Thus, in hyperinsulinemic states there is an accelerated loss of cell surface insulin receptors. In the present experiments we addressed this question in hypoinsulinemic states, in which insulin binding to cell surface receptors is generally increased. In hepatocytes obtained from hypoinsulinemic streptozotocin-induced diabetic rats, [ 125 I]iodoglucagon internalization was increased, while at the same time [ 125 I]iodoinsulin internalization was decreased. The defect in [ 125 I]iodoinsulin internalization was corrected by insulin treatment of the animal. In peripheral blood monocytes from patients with type I insulinopenic diabetes, internalization of [ 125 I]iodoinsulin was impaired; this defect was not present in insulin-treated patients. These data in the hypoinsulinemic rat and human diabetes suggest that receptor-mediated endocytosis is regulated in states of insulin deficiency as well as insulin excess. Delayed or reduced internalization of the insulin-receptor complex could amplify the muted signal caused by deficient hormone secretion

  11. Receptor-Mediated Melanoma Targeting with Radiolabeled α-Melanocyte-Stimulating Hormone: Relevance of the Net Charge of the Ligand

    Directory of Open Access Journals (Sweden)

    Alex N. Eberle

    2017-04-01

    Full Text Available A majority of melanotic and amelanotic melanomas overexpress melanocortin type 1 receptors (MC1Rs for α-melanocyte-stimulating hormone. Radiolabeled linear or cyclic analogs of α-MSH have a great potential as diagnostic or therapeutic tools for the management of malignant melanoma. Compounds such as [111In]DOTA-NAP-amide exhibit high affinity for the MC1R in vitro, good tumor uptake in vivo, but they may suffer from relatively high kidney uptake and retention in vivo. We have shown previously that the introduction of negative charges into radiolabeled DOTA-NAP-amide peptide analogs may enhance their excretion and reduce kidney retention. To address the question of where to place negative charges within the ligand, we have extended these studies by designing two novel peptides, Ac-Nle-Asp-His-d-Phe-Arg-Trp-Gly-Lys(DOTA-d-Asp-d-Asp-OH (DOTA-NAP-d-Asp-d-Asp with three negative charges at the C-terminal end (overall net charge of the molecule −2 and DOTA-Gly-Tyr(P-Nle-Asp-His-d-Phe-Arg-Trp-NH2 (DOTA-Phospho-MSH2-9 with two negative charges in the N-terminal region (net charge −1. The former peptide showed markedly reduced receptor affinity and biological activity by >10-fold compared to DOTA-NAP-amide as reference compound, and the latter peptide displayed similar bioactivity and receptor affinity as the reference compound. The uptake by melanoma tumor tissue of [111In]DOTA-Phospho-MSH2-9 was 7.33 ± 0.47 %ID/g 4 h after injection, i.e., almost equally high as with [111In]DOTA-NAP-amide. The kidney retention was 2.68 ± 0.18 %ID/g 4 h after injection and hence 44% lower than that of [111In]DOTA-NAP-amide. Over an observation period from 4 to 48 h, the tumor-to-kidney ratio of [111In]DOTA-Phospho-MSH2-9 was 35% more favorable than that of the reference compound. In a comparison of DOTA-NAP-d-Asp-d-Asp, DOTA-Phospho-MSH2-9 and DOTA-NAP-amide with five previously published analogs of DOTA-NAP-amide that altogether cover a range

  12. Quantitative analysis of receptor-mediated uptake and pro-apoptotic activity of mistletoe lectin-1 by high content imaging.

    Science.gov (United States)

    Beztsinna, N; de Matos, M B C; Walther, J; Heyder, C; Hildebrandt, E; Leneweit, G; Mastrobattista, E; Kok, R J

    2018-02-09

    Ribosome inactivating proteins (RIPs) are highly potent cytotoxins that have potential as anticancer therapeutics. Mistletoe lectin 1 (ML1) is a heterodimeric cytotoxic protein isolated from European Mistletoe and belongs to RIP class II. The aim of this project was to systematically study ML1 cell binding, endocytosis pathway(s), subcellular processing and apoptosis activation. For this purpose, state of the art cell imaging equipment and automated image analysis algorithms were used. ML1 displayed very fast binding to sugar residues on the membrane and energy-dependent uptake in CT26 cells. The co-staining with specific antibodies and uptake blocking experiments revealed involvement of both clathrin-dependent and -independent pathways in ML1 endocytosis. Co-localization studies demonstrated the toxin transport from early endocytic vesicles to Golgi network; a retrograde road to the endoplasmic reticulum. The pro-apoptotic and antiproliferative activity of ML1 were shown in time lapse movies and subsequently quantified. ML1 cytotoxicity was less affected in multidrug resistant tumor cell line 4T1 in contrast to commonly used chemotherapeutic drug (ML1 resistance index 6.9 vs 13.4 for doxorubicin; IC 50 : ML1 1.4 ng/ml vs doxorubicin 24000 ng/ml). This opens new opportunities for the use of ML1 as an alternative treatment in multidrug resistant cancers.

  13. Drosophila lipophorin receptors mediate the uptake of neutral lipids in oocytes and imaginal disc cells by an endocytosis-independent mechanism.

    Directory of Open Access Journals (Sweden)

    Esmeralda Parra-Peralbo

    2011-02-01

    Full Text Available Lipids are constantly shuttled through the body to redistribute energy and metabolites between sites of absorption, storage, and catabolism in a complex homeostatic equilibrium. In Drosophila, lipids are transported through the hemolymph in the form of lipoprotein particles, known as lipophorins. The mechanisms by which cells interact with circulating lipophorins and acquire their lipidic cargo are poorly understood. We have found that lipophorin receptor 1 and 2 (lpr1 and lpr2, two partially redundant genes belonging to the Low Density Lipoprotein Receptor (LDLR family, are essential for the efficient uptake and accumulation of neutral lipids by oocytes and cells of the imaginal discs. Females lacking the lpr2 gene lay eggs with low lipid content and have reduced fertility, revealing a central role for lpr2 in mediating Drosophila vitellogenesis. lpr1 and lpr2 are transcribed into multiple isoforms. Interestingly, only a subset of these isoforms containing a particular LDLR type A module mediate neutral lipid uptake. Expression of these isoforms induces the extracellular stabilization of lipophorins. Furthermore, our data indicate that endocytosis of the lipophorin receptors is not required to mediate the uptake of neutral lipids. These findings suggest a model where lipophorin receptors promote the extracellular lipolysis of lipophorins. This model is reminiscent of the lipolytic processing of triglyceride-rich lipoproteins that occurs at the mammalian capillary endothelium, suggesting an ancient role for LDLR-like proteins in this process.

  14. Hypothalamic kappa opioid receptor mediates both diet-induced and melanin concentrating hormone-induced liver damage through inflammation and endoplasmic reticulum stress.

    Science.gov (United States)

    Imbernon, Monica; Sanchez-Rebordelo, Estrella; Romero-Picó, Amparo; Kalló, Imre; Chee, Melissa J; Porteiro, Begoña; Al-Massadi, Omar; Contreras, Cristina; Fernø, Johan; Senra, Ana; Gallego, Rosalia; Folgueira, Cintia; Seoane, Luisa M; van Gestel, Margriet; Adan, Roger A; Liposits, Zsolt; Dieguez, Carlos; López, Miguel; Nogueiras, Ruben

    2016-10-01

    The opioid system is widely known to modulate the brain reward system and thus affect the behavior of humans and other animals, including feeding. We hypothesized that the hypothalamic opioid system might also control energy metabolism in peripheral tissues. Mice lacking the kappa opioid receptor (κOR) and adenoviral vectors overexpressing or silencing κOR were stereotaxically delivered in the lateral hypothalamic area (LHA) of rats. Vagal denervation was performed to assess its effect on liver metabolism. Endoplasmic reticulum (ER) stress was inhibited by pharmacological (tauroursodeoxycholic acid) and genetic (overexpression of the chaperone glucose-regulated protein 78 kDa) approaches. The peripheral effects on lipid metabolism were assessed by histological techniques and western blot. We show that in the LHA κOR directly controls hepatic lipid metabolism through the parasympathetic nervous system, independent of changes in food intake and body weight. κOR colocalizes with melanin concentrating hormone receptor 1 (MCH-R1) in the LHA, and genetic disruption of κOR reduced melanin concentrating hormone-induced liver steatosis. The functional relevance of these findings was given by the fact that silencing of κOR in the LHA attenuated both methionine choline-deficient, diet-induced and choline-deficient, high-fat diet-induced ER stress, inflammation, steatohepatitis, and fibrosis, whereas overexpression of κOR in this area promoted liver steatosis. Overexpression of glucose-regulated protein 78 kDa in the liver abolished hypothalamic κOR-induced steatosis by reducing hepatic ER stress. This study reveals a novel hypothalamic-parasympathetic circuit modulating hepatic function through inflammation and ER stress independent of changes in food intake or body weight; these findings might have implications for the clinical use of opioid receptor antagonists. (Hepatology 2016;64:1086-1104). © 2016 The Authors. (Hepatology published by Wiley Periodicals, Inc., on

  15. Relationship between local cerebral glucose uptakes, serum prolactin, growth hormone and cortisol levels changes during epilepsy

    International Nuclear Information System (INIS)

    Wang Mingfang; Mao Xianghui; Tang Ganghua; Zhao Jun; Sun Aijun

    2002-01-01

    Objective: To explore the relation of local cerebral FDG uptake value of glucose to the changes of prolactin (PRL), growth hormone (GH) and cortisol levels in serum during epilepsy. Methods: 76 epileptic patients with solitary epileptic focus were examined by 2-deoxy-2-[ 18 F] fluoro-D-glucose ( 18 F-FDG) positron emission tomography (PET) imaging and the FDG uptake value of epileptic foci were measured. Serum PRL, GH and cortisol levels of the patients were determined by radioimmunoassay (RIA) before and after seizures. Results: During ictal studies, all patients showed increased FDG uptake of epileptic foci compared with that in interictal phase. The serum PRL, GH and cortisol levels were significant higher after seizures. The changes of hormone levels correlated significantly with the lengths of seizure free intervals (SFIs) and with the types of seizures. But the variations of hormone levels had no relation with the site and FDG uptake of epileptic foci. In patients with absentia seizures, no significant increase was observed in serum PRL and cortisol levels. The changes of GH were not related with the types of seizures. Also, it was found that changes of hormone levels had significant relations to the lengths of SFIs. Conclusions: Serum PRL, GH and cortisol levels were significantly different before and after seizures. This study suggests that changes of postictal hormone levels correlated significantly with the types of seizures and lengths of SFIs, but the changes of hormone levels are not related with the site and FDG uptake of epileptic foci

  16. Radioiodine uptake and thyroid hormone levels on or off simultaneous carbimazole medication. A prospective paired comparison

    International Nuclear Information System (INIS)

    Walter, M.A.; Mueller-Brand, J.; Christ-Crain, M.; Mueller, B.

    2005-01-01

    Aim: To allow radioiodine (RAI) treatment in patients with need for anti-thyroid drug medication and low RAI uptakes we investigated the feasibility of discontinuing carbimazole for 3 days to enhance the RAI uptake without concurrent exacerbation of hyperthyroidism. Methods: We prospectively investigated RAI dynamics and thyroid hormone concentration in 12 patients with low RAI uptake ( 4 , T 3 and TSH were monitored. Results: Discontinuation of carbimazole for 3 days led to a significant increase of RAI uptake in all patients. We found an enhancement up to 4.9-fold compared to the measurement on carbimazole. The mean RAI uptake increased from 15.2±4.4% to 50.1±15.5% (p<0.001). The intrapersonal radioiodine half-life increased from 4.2±1.6 days to 5.4±0.7 days (p=0.13). Mean thyroid hormone concentration was not affected by the three day withdrawal of anti-thyroid drugs and no patient suffered from an aggravation of biochemical hyperthyroidism. Conclusion: A withdrawal of carbimazole for 3 days is long enough to provide sufficiently high RAI uptakes for RAI treatment in patients with low RAI uptakes and short enough to avoid the risk of exacerbation of hyperthyroidism. (orig.)

  17. Radioiodine uptake and thyroid hormone levels on or off simultaneous carbimazole medication. A prospective paired comparison

    Energy Technology Data Exchange (ETDEWEB)

    Walter, M.A.; Mueller-Brand, J. [Inst. of Nuclear Medicine, Univ. Hospital Basel (Switzerland); Christ-Crain, M.; Mueller, B. [Div. of Endocrinology, Univ. Hospital Basel (Switzerland)

    2005-02-01

    Aim: To allow radioiodine (RAI) treatment in patients with need for anti-thyroid drug medication and low RAI uptakes we investigated the feasibility of discontinuing carbimazole for 3 days to enhance the RAI uptake without concurrent exacerbation of hyperthyroidism. Methods: We prospectively investigated RAI dynamics and thyroid hormone concentration in 12 patients with low RAI uptake (<30%) under simultaneous carbimazole medication and 3 days after discontinuation. At both time points fT{sub 4}, T{sub 3} and TSH were monitored. Results: Discontinuation of carbimazole for 3 days led to a significant increase of RAI uptake in all patients. We found an enhancement up to 4.9-fold compared to the measurement on carbimazole. The mean RAI uptake increased from 15.2{+-}4.4% to 50.1{+-}15.5% (p<0.001). The intrapersonal radioiodine half-life increased from 4.2{+-}1.6 days to 5.4{+-}0.7 days (p=0.13). Mean thyroid hormone concentration was not affected by the three day withdrawal of anti-thyroid drugs and no patient suffered from an aggravation of biochemical hyperthyroidism. Conclusion: A withdrawal of carbimazole for 3 days is long enough to provide sufficiently high RAI uptakes for RAI treatment in patients with low RAI uptakes and short enough to avoid the risk of exacerbation of hyperthyroidism. (orig.)

  18. Ca uptake and its influence by growth hormone in osteoblasts of fetal rat calvaria

    International Nuclear Information System (INIS)

    Wang Hongfu; Jin Weifang; Sekimoto Haku

    1994-01-01

    Uptake and release of Ca 2+ are important functions of osteoblasts. In the paper we studied the uptake of calcium and influence by Growth Hormone in osteoblasts of fetal rat calvaria by liquid scintillation spectrometry of 45 Ca 2+ . In short-term cultures of the bone derived cells, the uptake of 45 Ca 2+ increased steadily. The activity of 45 Ca 2+ in the cells of 15 minute cultures was 2∼3 times of that in the 0 minute cultures. It continued to increase in the cells of 30 minute cultures. Exposure of the bone cells to GH at 55.3 ng/ml increased the uptake of 45 Ca 2+ by 2.3 times in the 30 minute cultures and 1.5 times in the 60 minute cultures than those of the control

  19. Carbamazepine (Tegretol) inhibits in vivo iodide uptake and hormone synthesis in rat thyroid glands

    International Nuclear Information System (INIS)

    Villa, S.M.; Alexander, N.M.

    1987-01-01

    Decreased serum concentrations of T3 and T4 occur in patients treated with the anticonvulsant drug carbamazepine (CBZ), but with rare exception, these patients remain euthyroid. The mechanism that accounts for diminished hormone levels is unknown, and our objective was to study the direct effect of CBZ on iodide uptake and hormone synthesis in thyroid glands of CBZ-treated and pair-fed control rats. Chronic ingestion (per os) of CBZ in male rats reduced the four hour thyroid 131I-iodide uptake by approximately 60%. This inhibition occurred after the animals had received sufficient CBZ to attain plasma CBZ concentrations of 0.8 microgram/ml. Continued treatment with CBZ ranging from 560 to 800 mg/kg/day for 14 days did not result in further inhibition of iodide uptake even though the plasma CBZ concentrations had increased 6-20 fold. No inhibition of iodide uptake was apparent when the animals initially received CBZ ranging from 40 to 152 mg/kg body weight for 22 days when there were no detectable levels of plasma CBZ. Overall growth rates of CBZ-treated rats were slightly (6-10%) less than the pair-fed control animals. Plasma T4 concentrations were reduced by 18% (p less than 0.05) in the CBZ-fed animals, while T3 concentrations were diminished by 53% (p less than 0.01). CBZ appeared to alter thyroidal iodide transport because the thyroid:plasma iodide ratios were decreased by 26% in the drug-treated rats. The distribution of radioiodine in thyroidal iodoamino acids was essentially the same in both groups of rats but the absolute quantities of radioiodine were more than 2.5 times greater in the control rats. CBZ failed to inhibit peroxidase-catalyzed iodide and guaiacol oxidation in vitro

  20. Receptor-mediated endocytosis of trichosanthin in choriocarcinoma cells

    International Nuclear Information System (INIS)

    Chan, W.Y.; Huang Hai; Tam, S.-C.

    2003-01-01

    Trichosanthin (TCS) is a ribosome inactivating protein (RIP). It is generally believed that its many biological activities act through inhibition of ribosomes resulting in a decrease in protein synthesis. It has been hypothesized that the rate of entry of TCS into cells to reach ribosomes is an important factor in determining its biological activity. To prove this hypothesis, we have mapped out and compared the intracellular routing of TCS in two cell lines, namely the choriocarcinoma JAR cell line, which is known to be highly sensitive to the toxic effects of TCS, and the hepatoma H35 cell line, to which TCS shows minimal toxicity. Results from laser scanning confocal microscopy indicated that fluorescein isothiocyanate labeled TCS quickly accumulated inside JAR cells within 4 h of incubation while only a low level of fluorescent signals was detected in H35 cells during the same period of time. When TCS was conjugated with gold particles (Au) and its intracellular locations were traced with a transmission electron microscope, it was found that most of TCS were bound to coated pits on the JAR cell surface and were rapidly internalized within an hour. By 4 h, TCS reached almost every cytoplasmic region including ribosomes, and the JAR cell began to degenerate. In H35 cells, however, the binding of TCS to coated pits was not observed, but instead, a small amount of TCS was found to penetrate the cell non-specifically by direct diffusion across the cell membrane. Our observations suggest that most of TCS enter JAR cells via a specific receptor mediated pathway, which allows a swift transport of TCS across the membrane and a rapid accumulation of intracellular TCS, while in H35 cells, TCS takes a slow and non-specific route. The receptor-mediated uptake together with the specific intracellular routing of TCS may partly account for the differential vulnerability of the choriocarcinoma cell line towards the toxicity of TCS

  1. Growth-hormone and somatostatin effects on [75Se]selenomethionine uptake by the pancreas

    International Nuclear Information System (INIS)

    Atkins, H.L.; Som, P.

    1979-01-01

    The imaging of the pancreas with [ 75 Se]selenomethionine has a low rate of reliability. This study was carried out in order to elucidate some factors that may be important in affecting the degree of uptake of the tracer by the pancreas. Studies were carried out in animals to observe the effects of growth-hormone (GH), somatostatin (SRIF), L-DOPA, and apomorphine administration on the distribution of [ 75 Se]selenomethionine. Intravenously administered GH significantly depressed pancreatic uptake of Se-75 in mice and dogs and depressed the pancreas-to-liver concentration ratio (P/L). The effect of i.p. GH in mice was to decrease the P/L ratio, but the decrease in pancreatic uptake was not statistically significant. There was also a greater effect of GH in dogs than in mice, with pancreatic uptake decreasing from 5.60 +- 2.17% to 1.24 +- 0.96% and the P/L from 4.78 +- 1.85 to 0.97 +- 0.73. L-DOPA and apomorphine produced effects similar to GH in mice. SRIF in small doses had little effect, but in larger doses it enhanced pancreatic uptake, although not affecting P/L. The results indicate that hypothalamic factors may be important in affecting the function of the exocrine pancreas. Both L-DOPA and apomorphine are known to stimulate GH production through hypothalamic-pituitary pathways. In addition to suppressing GH release, SRIF may have direct effects on the exocrine pancreas

  2. In uncontrolled diabetes, thyroid hormone and sympathetic activators induce thermogenesis without increasing glucose uptake in brown adipose tissue.

    Science.gov (United States)

    Matsen, Miles E; Thaler, Joshua P; Wisse, Brent E; Guyenet, Stephan J; Meek, Thomas H; Ogimoto, Kayoko; Cubelo, Alex; Fischer, Jonathan D; Kaiyala, Karl J; Schwartz, Michael W; Morton, Gregory J

    2013-04-01

    Recent advances in human brown adipose tissue (BAT) imaging technology have renewed interest in the identification of BAT activators for the treatment of obesity and diabetes. In uncontrolled diabetes (uDM), activation of BAT is implicated in glucose lowering mediated by intracerebroventricular (icv) administration of leptin, which normalizes blood glucose levels in streptozotocin (STZ)-induced diabetic rats. The potent effect of icv leptin to increase BAT glucose uptake in STZ-diabetes is accompanied by the return of reduced plasma thyroxine (T4) levels and BAT uncoupling protein-1 (Ucp1) mRNA levels to nondiabetic controls. We therefore sought to determine whether activation of thyroid hormone receptors is sufficient in and of itself to lower blood glucose levels in STZ-diabetes and whether this effect involves activation of BAT. We found that, although systemic administration of the thyroid hormone (TR)β-selective agonist GC-1 increases energy expenditure and induces further weight loss in STZ-diabetic rats, it neither increased BAT glucose uptake nor attenuated diabetic hyperglycemia. Even when GC-1 was administered in combination with a β(3)-adrenergic receptor agonist to mimic sympathetic nervous system activation, glucose uptake was not increased in STZ-diabetic rats, nor was blood glucose lowered, yet this intervention potently activated BAT. Similar results were observed in animals treated with active thyroid hormone (T3) instead of GC-1. Taken together, our data suggest that neither returning normal plasma thyroid hormone levels nor BAT activation has any impact on diabetic hyperglycemia, and that in BAT, increases of Ucp1 gene expression and glucose uptake are readily dissociated from one another in this setting.

  3. Thyroid hormone uptake and T4 derived T3 formation in different skeletal muscle types of normal and hyperthyroid rats

    International Nuclear Information System (INIS)

    Hardeveld, C. van; Kassenaar, A.A.H.

    1978-01-01

    In this study hind-limb perfusion was used to investigate conversion of T 4 to T 3 in skeletal muscle tissue. For this purpose the rats were depleted of thyroid hormones by thyroid ablation with 0.75 mCi 131 I and were perfused 2 weeks later, when the skeletal muscle tissue consumed oxygen at a normal rate due to one subcutaneous dose of 10 μg T 3 /100 g b. w. 3 days before the perfusion experiments were started. T 4 * of high specific activity (> 2000 μCi/μg) was added to the perfusate. In the muscle (mixed type) a mean T 4 → T 3 conversion of 2% (range 0.5-3.9) was found after 120 min of perfusion. T 3 generation from T 4 in skeletal muscle did not correspond with T 3 muscle uptake. This observation makes a significant overestimation of T 3 by selective uptake of a small contamination of T 3 * in the T 4 * preparation highly improbable. In red muscle the T 4 and T 3 uptake was about 50 % higher than in white muscle. The observed Tetracsup(c) and T 3 sup(c) were significantly higher in red than in white muscle. The uptake of thyroid hormones by both muscle types was not changed in hyperthyroid rats. The Tetrac and T 3 formation from T 4 , however, was increased in red muscles of hyperthyroid rats. The results show that thyroid hormone metabolism can vary markedly depending upon the type of muscle studied and they present a basis for a better understanding of clinical and biochemical evidence for a different susceptibility of red and white muscle fibers to thyroid hormones. (Abbreviations: *= 125 I; **= 131 I; T 3 sup(c)=T 4 derived T 3 ; Tetracsup(c)=T 4 derived Tetrac) (author)

  4. Understanding magnetic nanoparticle osteoblast receptor-mediated endocytosis using experiments and modeling

    International Nuclear Information System (INIS)

    Tran, Nhiem; Webster, Thomas J

    2013-01-01

    Iron oxide nanoparticles are promising candidates for controlling drug delivery through an external magnetic force to treat a wide range of diseases, including osteoporosis. Previous studies have demonstrated that in the presence of hydroxyapatite coated magnetite (Fe 3 O 4 ) nanoparticles, osteoblast (or bone forming cell) proliferation and long-term functions (such as calcium deposition) were significantly enhanced. Hydroxyapatite is the major inorganic component of bone. As a further attempt to understand why, in the current study, the uptake of such nanoparticles into osteoblasts was experimentally investigated and mathematically modeled. Magnetite nanoparticles were synthesized using a co-precipitation method and were coated with hydroxyapatite. A cellular uptake experiment at low temperatures indicated that receptor-mediated endocytosis contributed to the internalization of the magnetic nanoparticles into osteoblasts. A model was further developed to explain the uptake of magnetic nanoparticles into osteoblasts using receptor-mediated endocytosis. This model may explain the internalization of hydroxyapatite into osteoblasts to elevate intracellular calcium levels necessary to promote osteoblast functions to treat a wide range of orthopedic problems, including osteoporosis. (paper)

  5. 18F FDG Uptake of Human Testis on PET/CT: Correlation with Age, Sex Hormones, and Vasectomy

    International Nuclear Information System (INIS)

    Moon, Seung Hwan; Eo, Jae Sun; Lee, Jong Jin; Chung, June Key; Lee, Dong Soo; Lee, Myung Chul

    2011-01-01

    The purpose of this study was to evaluate glucose metabolism of normal human testis on 18F FDG PET/CT and to assess possible correlation among age, the serum levels of sex hormones, and vasectomy. 18F FDG PET/CT was performed in 66 normal healthy men (50.8±13.6 years, range 22-81), and mean standard uptake values (SUV) of 18F FDG in testis and adductor muscle were measured. Testis muscle SUV ratios (T/M ratios) were calculated. Serum levels of total testosterone, free testosterone, estradiol, and of sex hormone binding globulin (SHBG) were measured. We searched for correlations between T/M ratios and age and the serum concentrations of sex hormones. 18F FDG PET/CT was also performed in 32 vasectomized men (55.7±7.8 years, range 38-71) and 52 nonvasectomized men (55.4±11.6 years, range 37-72). Mean SUVs of testis and adductor muscle were measured, and T/M ratios were calculated. A significant age related decline was found in T/M ratio (r=-0.509, p 18F FDG uptake may have attributed to testicular function and testicular histology. Our findings may have important implications for the interpretation of testicular 18F FDG uptake in the normal adult population.

  6. {sup 18F} FDG Uptake of Human Testis on PET/CT: Correlation with Age, Sex Hormones, and Vasectomy

    Energy Technology Data Exchange (ETDEWEB)

    Moon, Seung Hwan; Eo, Jae Sun; Lee, Jong Jin; Chung, June Key; Lee, Dong Soo; Lee, Myung Chul [Seoul National Univ. Hospital, Seoul (Korea, Republic of)

    2011-12-15

    The purpose of this study was to evaluate glucose metabolism of normal human testis on {sup 18F} FDG PET/CT and to assess possible correlation among age, the serum levels of sex hormones, and vasectomy. {sup 18F} FDG PET/CT was performed in 66 normal healthy men (50.8{+-}13.6 years, range 22-81), and mean standard uptake values (SUV) of {sup 18F} FDG in testis and adductor muscle were measured. Testis muscle SUV ratios (T/M ratios) were calculated. Serum levels of total testosterone, free testosterone, estradiol, and of sex hormone binding globulin (SHBG) were measured. We searched for correlations between T/M ratios and age and the serum concentrations of sex hormones. {sup 18F} FDG PET/CT was also performed in 32 vasectomized men (55.7{+-}7.8 years, range 38-71) and 52 nonvasectomized men (55.4{+-}11.6 years, range 37-72). Mean SUVs of testis and adductor muscle were measured, and T/M ratios were calculated. A significant age related decline was found in T/M ratio (r=-0.509, p<0.0001). Serum levels of total testosterone and free testosterone were also found to be positively correlated with T/M ratio (r=-0.427, p=0.0003; r=0.435, p=0.0003, respectively). The mean SUV and T/M ratio of vasectomized men were significantly lower than those of nonvasectomized men (p<0.0378 and p=0.0001, respectively). Glucose metabolism in the testis in an adult population was found to be correlated with age, serum sex hormone level, and vasectomy history. These results indicate that testicular {sup 18F} FDG uptake may have attributed to testicular function and testicular histology. Our findings may have important implications for the interpretation of testicular {sup 18F} FDG uptake in the normal adult population.

  7. Hormones

    Science.gov (United States)

    Hormones are your body's chemical messengers. They travel in your bloodstream to tissues or organs. They work ... glands, which are special groups of cells, make hormones. The major endocrine glands are the pituitary, pineal, ...

  8. High prevalence of thyroid FDG uptake on PET study in patients with thyroid hormone replacement

    International Nuclear Information System (INIS)

    Yu, J.-Q.; Kumar, R.; Xiu, Y.; Dadparvar, S.; Kung, J.W.; Kunjunmen, B.D.; Feng, Q.; Alavi, A.; Zhuang, H.

    2004-01-01

    Thyroid uptake is commonly seen on whole-body FDG-PET images. One well-known cause for this uptake is hyperthyroidism. The purpose of this study was to determine whether hypothyroidism also affects FDG uptake by the thyroid gland. Hospital records of 2765 patients who had undergone whole-body FDG-PET imaging for malignancies were retrospectively reviewed. Among them, those who had thyroid cancer, history of thyroid ablation for hyperthyroidism, neck lymphoma, and other types of head and neck cancer or recent neck surgery were excluded from analysis. The prevalence and level of thyroid FDG uptake in the remaining 1939 patients was compared with the state of patients' thyroid function. There were 141 hypothyroid subjects and the rest (n=1798) were euthyroid. The prevalence of thyroid tissue uptake in euthyroid subjects was 2.34% (42 of 1798), while it was 22% (31 out of 141) in hypothyroid patients. This was statistically significant. Similarly, the prevalence of hypothyroidism in patients in patients showing thyroid uptake was 42.5% (31 of 73), while it was 5.9% (110 of 1866) in patients without thyroid uptake. This was again statistically significant (p<0.001). Based on this retrospective analysis it was concluded that the prevalence of increased thyroid FDG uptake is significantly higher in patients with hypothyroidism than those who are euthyroid. (author)

  9. Multifunctional pH-Responsive Folate Receptor Mediated Polymer Nanoparticles for Drug Delivery.

    Science.gov (United States)

    Cai, Xiaoqing; Yang, Xiaoye; Wang, Fang; Zhang, Chen; Sun, Deqing; Zhai, Guangxi

    2016-07-01

    Multifunctional pH-responsive folate receptor mediated targeted polymer nanoparticles (TPNps) were developed for docetaxel (DTX) delivery based on poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol)poly (β-amino ester) (P123-PAE) and poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol)-folate (P123-FA) copolymers. The DTX was loaded into the TPNps with a decent drug loading content of 15.02 ± 0.14 wt%. In vitro drug release results showed that the DTX was released from the TPNps at a pH-dependent manner. Tetrazolium dye (MTT) assay revealed that the bland polymer nanoparticles displayed almost nontoxicity at 200 μg/mL concentration. However, the DTX-loaded TPNps showed high anti-tumor activity at low IC50 (0.72 μg/mL) for MCF-7 cells following 48 h incubation. Cellular uptake experiments revealed that the TPNps had higher degree of cellular uptake than nontargeted polymer nanoparticles, indicating that the nanoparticles were internalized into the cells via FA receptor-mediated endocytosis. Moreover, the cellular uptake pathways for the FA grafted polymer were involved in energy-dependent, clathrin-mediated and caveolae-mediated endocytosis. The cell killing effect and cellular uptake of the DTX-TPNps by the MCF-7 cells were all enhanced by about two folds at pH 5.5 when compared with pH 7.4. The TPNps also significantly prolonged the in vivo retention time for the DTX. These results suggest that the biocompatible pH responsive folate-modified polymer nanoparticles present a promising safe nanosystem for intracellular targeted delivery of DTX.

  10. Effect of an insect juvenile hormone analogue, Fenoxycarb on development and oxygen uptake by larval lobsters Homarus gammarus (L.).

    Science.gov (United States)

    Arnold, Katie E; Wells, Colin; Spicer, John I

    2009-04-01

    Little attention has been focused on the effect of anthropogenic compounds that disrupt the endocrine systems in crustaceans. Consequently, this study investigated the effects of the juvenile hormone analogue (JHA), Fenoxycarb on selected physiological and developmental processes of the zoeal stages in the European lobster, Homarus gammarus. Chronic exposure to Fenoxycarb (50microg L(-1)) resulted in a significant (p < 0.05) reduction in moult frequency and size at moult. Fenoxycarb exposure extended zoeal duration between zoea I to II (p<0.05) and resulted in total inhibition of the moult from zoea II to III. Significantly greater rates of O2 uptake were observed in Fenoxycarb-exposed larvae in comparison with controls (p<0.05). All rates of O2 uptake decreased significantly between 7 and 12d of exposure (p<0.05). At 12d, exposure to the solvent control no longer influenced rates of O2 uptake, but it was not possible to attribute increased O2 uptake to Fenoxycarb exposure directly, as treated individuals did not moult beyond zoea III. The low exposure concentrations of Fenoxycarb, comparable to those used in plant protection, resulted in endocrine disrupted responses in H. gammarus (albeit with little clear, demonstrable effect on metabolism) a finding that could have important ecological and commercial implications.

  11. effect of plant hormones on the growth and nutrient uptake of maize

    African Journals Online (AJOL)

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    Key words/phrases: Acidic soils, exogenous plant hormones, liming, neutral compost, placed applica- tion .... placed into plastic pots of 18 and 10 cm upper and ... 0.61. *15 ml pot-1 mixture of micronutrient elements were added.

  12. Induction of aryl hydrocarbon receptor-mediated and estrogen receptor-mediated activities, and modulation of cell proliferation by dinaphthofurans

    Czech Academy of Sciences Publication Activity Database

    Vondráček, Jan; Chramostová, Kateřina; Plíšková, M.; Bláha, L.; Brack, W.; Kozubík, Alois; Machala, M.

    2004-01-01

    Roč. 23, č. 9 (2004), s. 2214-2220 ISSN 0730-7268 R&D Projects: GA ČR GA525/03/1527 Institutional research plan: CEZ:AV0Z5004920 Keywords : aryl hydrocarbon receptor-mediated activity * estrogenicity * intercellular communication inhibition Subject RIV: BO - Biophysics Impact factor: 2.121, year: 2004

  13. Receptor-mediated gene delivery using chemically modified chitosan

    International Nuclear Information System (INIS)

    Kim, T H; Jiang, H L; Nah, J W; Cho, M H; Akaike, T; Cho, C S

    2007-01-01

    Chitosan has been investigated as a non-viral vector because it has several advantages such as biocompatibility, biodegradability and low toxicity with high cationic potential. However, the low specificity and low transfection efficiency of chitosan need to be solved prior to clinical application. In this paper, we focused on the galactose or mannose ligand modification of chitosan for enhancement of cell specificity and transfection efficiency via receptor-mediated endocytosis in vitro and in vivo

  14. Reducing renal uptake of 9Y- and 177Lu-labeled alpha-melanocyte stimulating hormone peptide analogues

    International Nuclear Information System (INIS)

    Miao Yubin; Fisher, Darrell R.; Quinn, Thomas P.

    2006-01-01

    Objective: The purpose of this study was to improve the tumor-to-kidney uptake ratios of 9 Y- and 177 Lu-[1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-Re-Cys 3,4,1 , D-Phe 7 , Arg 11 ]α-melanocyte stimulating hormone 3-13 {DOTA-Re(Arg 11 )CCMSH} through coupling a negatively charged glutamic acid (Glu) to the peptide sequence. Methods: A new peptide of DOTA-Re(Glu 2 , Arg 11 )CCMSH was designed, synthesized and labeled with 9 Y and 177 Lu. Pharmacokinetics of 9 Y- and 177 Lu-DOTA-Re(Glu 2 , Arg 11 )CCMSH was determined in B16/F1 murine melanoma-bearing C57 mice. Results: 9 Y- and 177 Lu-DOTA-Re(Glu 2 , Arg 11 )CCMSH exhibited significantly (P 9 Y- and 177 Lu-DOTA-Re(Arg 11 )CCMSH at 30 min and at 2, 4 and 24 h after dose administration. The renal uptake values of 9 Y- and 177 Lu-DOTA-Re(Glu 2 , Arg 11 )CCMSH were 28.16% and 28.81% of those of 9 Y- and 177 Lu-DOTA-Re(Arg 11 )CCMSH, respectively, at 4 h postinjection. 9 Y- and 177 Lu-DOTA-Re(Glu 2 , Arg 11 )CCMSH displayed higher tumor-to-kidney uptake ratios than 9 Y- and 177 Lu-DOTA-Re(Arg 11 )CCMSH at 30 min and at 2, 4 and 24 h after dose administration. The tumor-to-kidney uptake ratio of 9 Y- and 177 Lu-DOTA-Re(Glu 2 , Arg 11 )CCMSH was 2.28 and 1.69 times of 9 Y- and 177 Lu-DOTA-Re(Arg 11 )CCMSH, respectively, at 4 h postinjection. The 9 Y- and 177 Lu-DOTA-Re(Glu 2 , Arg 11 )CCMSH activity accumulation was low in normal organs except for kidney. Conclusions: Coupling a negatively charged amino acid (Glu) to the CCMSH peptide sequence dramatically reduced the renal uptake values and increased the tumor-to-kidney uptake ratios of 9 Y- and 177 Lu-DOTA-Re(Glu 2 , Arg 11 )CCMSH, facilitating their potential applications as radiopharmaceuticals for targeted radionuclide therapy of melanoma

  15. In vitro binding and receptor-mediated activity of terlipressin at vasopressin receptors V1 and V2.

    Science.gov (United States)

    Jamil, Khurram; Pappas, Stephen Chris; Devarakonda, Krishna R

    2018-01-01

    Terlipressin, a synthetic, systemic vasoconstrictor with selective activity at vasopressin-1 (V 1 ) receptors, is a pro-drug for the endogenous/natural porcine hormone [Lys 8 ]-vasopressin (LVP). We investigated binding and receptor-mediated cellular activities of terlipressin, LVP, and endogenous human hormone [Arg 8 ]-vasopressin (AVP) at V 1 and vasopressin-2 (V 2 ) receptors. Cell membrane homogenates of Chinese hamster ovary cells expressing human V 1 and V 2 receptors were used in competitive binding assays to measure receptor-binding activity. These cells were used in functional assays to measure receptor-mediated cellular activity of terlipressin, LVP, and AVP. Binding was measured by [ 3 H]AVP counts, and the activity was measured by fluorometric detection of intracellular calcium mobilization (V 1 ) and cyclic adenosine monophosphate (V 2 ). Binding potency at V 1 and V 2 was AVP>LVP>terlipressin. LVP and terlipressin had approximately sixfold higher affinity for V 1 than for V 2 . Cellular activity potency was also AVP>LVP>terlipressin. Terlipressin was a partial agonist at V 1 and a full agonist at V 2 ; LVP was a full agonist at both V 1 and V 2 . The in vivo response to terlipressin is likely due to the partial V 1 agonist activity of terlipressin and full V 1 agonist activity of its metabolite, LVP. These results provide supportive evidence for previous findings and further establish terlipressin pharmacology for vasopressin receptors.

  16. Stronger Dopamine D1 Receptor-Mediated Neurotransmission in Dyskinesia.

    Science.gov (United States)

    Farré, Daniel; Muñoz, Ana; Moreno, Estefanía; Reyes-Resina, Irene; Canet-Pons, Júlia; Dopeso-Reyes, Iria G; Rico, Alberto J; Lluís, Carme; Mallol, Josefa; Navarro, Gemma; Canela, Enric I; Cortés, Antonio; Labandeira-García, José L; Casadó, Vicent; Lanciego, José L; Franco, Rafael

    2015-12-01

    Radioligand binding assays to rat striatal dopamine D1 receptors showed that brain lateralization of the dopaminergic system were not due to changes in expression but in agonist affinity. D1 receptor-mediated striatal imbalance resulted from a significantly higher agonist affinity in the left striatum. D1 receptors heteromerize with dopamine D3 receptors, which are considered therapeutic targets for dyskinesia in parkinsonian patients. Expression of both D3 and D1-D3 receptor heteromers were increased in samples from 6-hydroxy-dopamine-hemilesioned rats rendered dyskinetic by treatment with 3, 4-dihydroxyphenyl-L-alanine (L-DOPA). Similar findings were obtained using striatal samples from primates. Radioligand binding studies in the presence of a D3 agonist led in dyskinetic, but not in lesioned or L-DOPA-treated rats, to a higher dopamine sensitivity. Upon D3-receptor activation, the affinity of agonists for binding to the right striatal D1 receptor increased. Excess dopamine coming from L-DOPA medication likely activates D3 receptors thus making right and left striatal D1 receptors equally responsive to dopamine. These results show that dyskinesia occurs concurrently with a right/left striatal balance in D1 receptor-mediated neurotransmission.

  17. Receptor-mediated endocytosis of lysozyme in renal proximal tubules of the frog Rana temporaria

    Directory of Open Access Journals (Sweden)

    E.V. Seliverstova

    2015-04-01

    Full Text Available The mechanism of protein reabsorption in the kidney of lower vertebrates remains insufficiently investigated in spite of raising interest to the amphibian and fish kidneys as a useful model for physiological and pathophysiological examinations. In the present study, we examined the renal tubular uptake and the internalization rote of lysozyme after its intravenous injection in the wintering frog Rana temporaria using immunohisto- and immunocytochemistry and specific markers for some endocytic compartments. The distinct expression of megalin and cubilin in the proximal tubule cells of lysozyme-injected frogs was revealed whereas kidney tissue of control animals showed no positive immunoreactivity. Lysozyme was detected in the apical endocytic compartment of the tubular cells and colocalized with clathrin 10 min after injection. After 20 min, lysozyme was located in the subapical compartment negative to clathrin (endosomes, and intracellular trafficking of lysozyme was coincided with the distribution of megalin and cubilin. However, internalized protein was retained in the endosomes and did not reach lysosomes within 30 min after treatment that may indicate the inhibition of intracellular trafficking in hibernating frogs. For the first time, we provided the evidence that lysozyme is filtered through the glomeruli and absorbed by receptor-mediated clathrin-dependent endocytosis in the frog proximal tubule cells. Thus, the protein uptake in the amphibian mesonephros is mediated by megalin and cubilin that confirms a critical role of endocytic receptors in the renal reabsorption of proteins in amphibians as in mammals.

  18. Receptor-mediated mechanism for the transport of prolactin from blood to cerebrospinal fluid

    International Nuclear Information System (INIS)

    Walsh, R.J.; Slaby, F.J.; Posner, B.I.

    1987-01-01

    Prolactin (PRL) interacts with areas of the central nervous system which reside behind the blood-brain barrier. While vascular PRL does not cross this barrier, it is readily accessible to the cerebrospinal fluid (CSF) from which it may gain access to the PRL-responsive areas of the brain. Studies were undertaken to characterize the mechanism responsible for the translocation of PRL from blood to CSF. Rats were given external jugular vein injections of [ 125 -I]iodo-PRL in the presence or absence of an excess of unlabeled ovine PRL (oPRL), human GH, bovine GH, or porcine insulin. CSF and choroid plexus were removed 60 min later. CSF samples were electrophoresed on sodium dodecyl sulfate-polyacrylamide slab gels and resultant autoradiographs were analyzed with quantitative microdensitometry. The data revealed that unlabeled lactogenic hormones, viz. oPRL and human GH, caused a statistically significant inhibition of [ 125 I]iodo-PRL transport from blood to CSF. In contrast, nonlactogenic hormones, viz bovine GH and insulin, had no effect on [ 125 I]iodo-PRL transport into the CSF. An identical pattern of competition was observed in the binding of hormone to the choroid plexus. Furthermore, vascular injections of [ 125 I]iodo-PRL administered with a range of concentrations of unlabeled oPRL revealed a dose-response inhibition in the transport of [ 125 I]iodo-PRL from blood to CSF. The study demonstrates that PRL enters the CSF by a specific, PRL receptor-mediated transport mechanism. The data is consistent with the hypothesis that the transport mechanism resides at the choroid plexus. The existence of this transport mechanism reflects the importance of the cerebroventricular system in PRL-brain interactions

  19. DMPD: Modulation of Toll-interleukin 1 receptor mediated signaling. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 15662540 Modulation of Toll-interleukin 1 receptor mediated signaling. Li X, Qin J.... J Mol Med. 2005 Apr;83(4):258-66. Epub 2005 Jan 21. (.png) (.svg) (.html) (.csml) Show Modulation of Toll-i...nterleukin 1 receptor mediated signaling. PubmedID 15662540 Title Modulation of Toll-interleukin 1 receptor

  20. Effect of hypophysectomy and hormonal replacement on the uptake of Tc-99m methylene diphosphonate in the metaphysis and shaft of the rat femur: concise communication

    International Nuclear Information System (INIS)

    Trow, R.S.; Klingensmith, G.J.; Klingensmith, W.C.; Huffer, W.E.; Schalch, D.S.

    1983-01-01

    We have investigated the uptake of Tc-99m methylene diphosphonate (Tc-MDP) in the metaphysis and shaft of the rat femur as affected by hypophysectomy and hormonal replacement with growth hormone and thyroxine. Two hours following injection of Tc-MDP, the metaphysis and a specimen of shaft were obtained and the metaphysis-to-shaft radioactivity ratio was measured. By five days after hypophysectomy the metaphysis-to-shaft ratio fell from a control value of 3.8 +/- 0.2 (mean +/- s.e.) to 2.4 +/- 0.2 (p less than 0.05) and remained significantly decreased throughout the 30-day study. When daily hormonal replacement with 0.5 mg of bovine growth hormone and 10 micrograms of thyroxine (both administered intraperitoneally) was given, beginning on the eighth day after hypophysectomy, the metaphysis-to-shaft ratio of Tc-MDP returned to control levels in twelve days. This model demonstrates the effect of growth hormone and thyroxine on the distribution of Tc-MDP, and may be useful as a radiobioassay of net circulating skeletal growth-promoting activity

  1. Killing of intracellular Mycobacterium tuberculosis by receptor-mediated drug delivery

    International Nuclear Information System (INIS)

    Majumdar, S.; Basu, S.K.

    1991-01-01

    p-Aminosalicylic acid (PAS) conjugated to maleylated bovine serum albumin (MBSA) was taken up efficiently through high-affinity MBSA-binding sites on macrophages. Binding of the radiolabeled conjugate to cultured mouse peritoneal macrophages at 4 degrees C was competed for by MBSA but not by PAS. At 37 degrees C, the radiolabeled conjugate was rapidly degraded by the macrophages, leading to release of acid-soluble degradation products in the medium. The drug conjugate was nearly 100 times as effective as free PAS in killing the intracellular mycobacteria in mouse peritoneal macrophages infected in culture with Mycobacterium tuberculosis. The killing of intracellular mycobacteria mediated by the drug conjugate was effectively prevented by simultaneous addition of excess MBSA (100 micrograms/ml) or chloroquine (3 microM) to the medium, whereas these agents did not affect the microbicidal action of free PAS. These results suggest that (i) uptake of the PAS-MBSA conjugate was mediated by cell surface receptors on macrophages which recognize MBSA and (ii) lysosomal hydrolysis of the internalized conjugate resulted in intracellular release of a pharmacologically active form of the drug, which led to selective killing of the M. tuberculosis harbored by mouse macrophages infected in culture. This receptor-mediated modality of delivering drugs to macrophages could contribute to greater therapeutic efficacy and minimization of toxic side effects in the management of tuberculosis and other intracellular mycobacterial infections

  2. Effects of recombinant eel growth hormone on the uptake of ( sup 35 S)sulfate by ceratobranchial cartilages of the Japanese eel, Anguilla japonica

    Energy Technology Data Exchange (ETDEWEB)

    Duan, C.M.; Inui, Y. (Univ. of Tokyo (Japan))

    1990-08-01

    Effects of growth hormone (GH) on the synthesis of mucopolysaccharide by ceratobranchial cartilages of the Japanese eel, Anguilla japonica, were examined by monitoring the in vitro uptake of ({sup 35}S)sulfate. The ({sup 35}S)sulfate uptake decreased rapidly to one-third of the initial level during the first 3 days after hypophysectomy, and decreased gradually thereafter. When hypophysectomized eels were injected intramuscularly with recombinant eel GH (2 micrograms/g), the plasma GH concentrations increased maximally after 6 hr, and declined rapidly thereafter. On the other hand, the sulfate uptake increased significantly after 12 hr, and high levels were maintained until 48 hr. The stimulating effect of GH was dose dependent (0.02-2 micrograms/g). However, the addition of eel GH (0.05-5 micrograms/ml) to the culture medium did not affect the sulfate uptake by hypophysectomized eel cartilages, suggesting that the stimulative action of GH on the sulfate uptake by the cartilages is indirect.

  3. The Impact of Energy Substrates, Hormone Level and Subject-Related Factors on Physiologic Myocardial {sup 18}F-FDG Uptake in Normal Humans

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Juhye; Kong, Eunjung; Chun, Kyungah; Cho, Ihnho [Yeung-Nam Univ. Hoepital, Daegu (Korea, Republic of)

    2013-12-15

    In a whole-body {sup 18}F-FDG PET/CT, non-specific {sup 18}F-FDG uptake of the myocardium is a common finding and can be very variable, ranging from background activity to intense accumulation and inhomogeneity. We investigated the effect of energy substrates and plasma/serum hormones that may have an influence on myocardial {sup 18}F-FDG uptake. F-FDG PET/CT was performed on 100 normal volunteers from November 2007 to August 2008. Blood samples were taken just before {sup 18}F-FDG injection from all subjects. Myocardial {sup 18}F-FDG uptake was measured as the mean (SUVmean) and maximal (SUV{sub max}) standardized uptake value. The myocardium was delineated on the PET/CT image by a manual volume of interest (VOI).We analyzed the influence of age, sex, presence of diabetes, fasting duration, insulin, glucagon, fasting glucose, lactate, free fatty acid (FFA), epinephrine (EPi), norepinephrine (NEp), free triiodothyronine (T3), free thyroxine (T4), thyroid-stimulating hormone (TSH) and body mass index (BMI). Overall, 92 subjects (mean age 50.28±8.30, male 57) were enrolled. The average of myocardial SUVmean was 2.08 and of myocardial SUV{sub max} was 4.57, respectively and there was a strong linear correlation between SUVmean and SUV{sub max} (r =0.98). FFA and fasting duration showed significant negative correlation with myocardial {sup 18}F-FDG uptake, respectively (r =-0.40 in FFA; r =-0.41 in fasting duration). No significant relationships were observed between myocardial uptake and age, sex, presence of diabetics, insulin, glucagon, fasting glucose, lactate, EPi, NEp, free T3, free T4, TSH and BMI. Myocardial {sup 18}F-FDG uptake decreases with longer fasting duration and higher FFA level in normal humans. Modulating myocardial uptake could improve {sup 18}F-FDG PET/CT imaging for specific oncologic and cardiovascular indications.

  4. Receptor-Mediated Endocytosis and Brain Delivery of Therapeutic Biologics

    Directory of Open Access Journals (Sweden)

    Guangqing Xiao

    2013-01-01

    Full Text Available Transport of macromolecules across the blood-brain-barrier (BBB requires both specific and nonspecific interactions between macromolecules and proteins/receptors expressed on the luminal and/or the abluminal surfaces of the brain capillary endothelial cells. Endocytosis and transcytosis play important roles in the distribution of macromolecules. Due to the tight junction of BBB, brain delivery of traditional therapeutic proteins with large molecular weight is generally not possible. There are multiple pathways through which macromolecules can be taken up into cells through both specific and nonspecific interactions with proteins/receptors on the cell surface. This review is focused on the current knowledge of receptor-mediated endocytosis/transcytosis and brain delivery using the Angiopep-2-conjugated system and the molecular Trojan horses. In addition, the role of neonatal Fc receptor (FcRn in regulating the efflux of Immunoglobulin G (IgG from brain to blood, and approaches to improve the pharmacokinetics of therapeutic biologics by generating Fc fusion proteins, and increasing the pH dependent binding affinity between Fc and FcRn, are discussed.

  5. Somatostatin receptor-mediated imaging and therapy: basic science, current knowledge, limitations and future perspectives

    Energy Technology Data Exchange (ETDEWEB)

    Breeman, W.A.P.; Jong, M. de; Kwekkeboom, D.J.; Valkema, R.; Bakker, W.H.; Kooij, P.P.M. [Dept. of Nuclear Medicine, Erasmus Medical Centre Rotterdam (Netherlands); Visser, T.J. [Dept. of Internal Medicine, Erasmus Medical Centre Rotterdam (Netherlands); Krenning, E.P. [Dept. of Nuclear Medicine, Erasmus Medical Centre Rotterdam (Netherlands); Dept. of Internal Medicine, Erasmus Medical Centre Rotterdam (Netherlands)

    2001-09-01

    In vivo somatostatin receptor-mediated scintigraphy has proven to be a valuable method for the visualisation of neuroendocrine tumours and their metastases. A new application is the use of radiolabelled analogues for somatostatin receptor-mediated therapy. This paper presents a review on the basic science, historical background and current knowledge of somatostatin receptor subtypes and their expression in neuroendocrine tumours. New somatostatin analogues, new chelators, ''new'' radionuclides and combinations thereof are also discussed. Due attention is given to limitations and future perspectives of somatostatin receptor-mediated imaging and therapy. (orig.)

  6. Somatostatin receptor-mediated imaging and therapy: basic science, current knowledge, limitations and future perspectives

    International Nuclear Information System (INIS)

    Breeman, W.A.P.; Jong, M. de; Kwekkeboom, D.J.; Valkema, R.; Bakker, W.H.; Kooij, P.P.M.; Visser, T.J.; Krenning, E.P.

    2001-01-01

    In vivo somatostatin receptor-mediated scintigraphy has proven to be a valuable method for the visualisation of neuroendocrine tumours and their metastases. A new application is the use of radiolabelled analogues for somatostatin receptor-mediated therapy. This paper presents a review on the basic science, historical background and current knowledge of somatostatin receptor subtypes and their expression in neuroendocrine tumours. New somatostatin analogues, new chelators, ''new'' radionuclides and combinations thereof are also discussed. Due attention is given to limitations and future perspectives of somatostatin receptor-mediated imaging and therapy. (orig.)

  7. Scavenger receptors mediate the role of SUMO and Ftz-f1 in Drosophila steroidogenesis.

    Directory of Open Access Journals (Sweden)

    Ana Talamillo

    2013-04-01

    Full Text Available SUMOylation participates in ecdysteroid biosynthesis at the onset of metamorphosis in Drosophila melanogaster. Silencing the Drosophila SUMO homologue smt3 in the prothoracic gland leads to reduced lipid content, low ecdysone titers, and a block in the larval-pupal transition. Here we show that the SR-BI family of Scavenger Receptors mediates SUMO functions. Reduced levels of Snmp1 compromise lipid uptake in the prothoracic gland. In addition, overexpression of Snmp1 is able to recover lipid droplet levels in the smt3 knockdown prothoracic gland cells. Snmp1 expression depends on Ftz-f1 (an NR5A-type orphan nuclear receptor, the expression of which, in turn, depends on SUMO. Furthermore, we show by in vitro and in vivo experiments that Ftz-f1 is SUMOylated. RNAi-mediated knockdown of ftz-f1 phenocopies that of smt3 at the larval to pupal transition, thus Ftz-f1 is an interesting candidate to mediate some of the functions of SUMO at the onset of metamorphosis. Additionally, we demonstrate that the role of SUMOylation, Ftz-f1, and the Scavenger Receptors in lipid capture and mobilization is conserved in other steroidogenic tissues such as the follicle cells of the ovary. smt3 knockdown, as well as ftz-f1 or Scavenger knockdown, depleted the lipid content of the follicle cells, which could be rescued by Snmp1 overexpression. Therefore, our data provide new insights into the regulation of metamorphosis via lipid homeostasis, showing that Drosophila Smt3, Ftz-f1, and SR-BIs are part of a general mechanism for uptake of lipids such as cholesterol, required during development in steroidogenic tissues.

  8. Does the intensity of diffuse thyroid gland uptake on F-18 fluorodeoxyglucose positron emission tomography/computed tomography scan predict the severity of hypothyroidism? Correlation between maximal standardized uptake value and serum thyroid stimulating hormone levels

    International Nuclear Information System (INIS)

    Pruthi, Ankur; Choudhury, Partha Sarathi; Gupta, Manoj; Taywade, Sameer

    2015-01-01

    F-18 fluorodeoxyglucose (F-18 FDG) positron emission tomography/computed tomography (PET/CT) scan and hypothyroidism. The aim was to determine whether the intensity of diffuse thyroid gland uptake on F-18 FDG PET/CT scans predicts the severity of hypothyroidism. A retrospective analysis of 3868 patients who underwent F-18 FDG PET/CT scans, between October 2012 and June 2013 in our institution for various oncological indications was done. Out of them, 106 (2.7%) patients (79 females, 27 males) presented with bilateral diffuse thyroid gland uptake as an incidental finding. These patients were investigated retrospectively and various parameters such as age, sex, primary cancer site, maximal standardized uptake value (SUVmax), results of thyroid function tests (TFTs) and fine-needle aspiration cytology results were noted. The SUVmax values were correlated with serum thyroid stimulating hormone (S. TSH) levels using Pearson's correlation analysis. Pearson's correlation analysis. Clinical information and TFT (serum FT3, FT4 and TSH levels) results were available for 31 of the 106 patients (27 females, 4 males; mean age 51.5 years). Twenty-six out of 31 patients (84%) were having abnormal TFTs with abnormal TSH levels in 24/31 patients (mean S. TSH: 22.35 μIU/ml, median: 7.37 μIU/ml, range: 0.074-211 μIU/ml). Among 7 patients with normal TSH levels, 2 patients demonstrated low FT3 and FT4 levels. No significant correlation was found between maximum standardized uptake value and TSH levels (r = 0.115, P > 0.05). Incidentally detected diffuse thyroid gland uptake on F-18 FDG PET/CT scan was usually associated with hypothyroidism probably caused by autoimmune thyroiditis. Patients should be investigated promptly irrespective of the intensity of FDG uptake with TFTs to initiate replacement therapy and a USG examination to look for any suspicious nodules

  9. Alterations of serum concentrations of thyroid hormones and sex hormone-binding globulin, nuclear binding of tri-iodothyronine and thyroid hormone-stimulated cellular uptake of oxygen and glucose in mononuclear blood cells from patients with non-thyroidal illness

    DEFF Research Database (Denmark)

    Kvetny, J; Matzen, L

    1990-01-01

    Nuclear tri-iodothyronine (T3) binding and thyroid hormone-stimulated oxygen consumption and glucose uptake were examined in mononuclear blood cells from patients with non-thyroidal illness (NTI) in which serum T3 was significantly (P less than 0.05) depressed (0.62 +/- 0.12 (S.D.) nmol/l) compared...

  10. Fcγ receptor-mediated inflammation inhibits axon regeneration.

    Directory of Open Access Journals (Sweden)

    Gang Zhang

    Full Text Available Anti-glycan/ganglioside antibodies are the most common immune effectors found in patients with Guillain-Barré Syndrome, which is a peripheral autoimmune neuropathy. We previously reported that disease-relevant anti-glycan autoantibodies inhibited axon regeneration, which echo the clinical association of these antibodies and poor recovery in Guillain-Barré Syndrome. However, the specific molecular and cellular elements involved in this antibody-mediated inhibition of axon regeneration are not previously defined. This study examined the role of Fcγ receptors and macrophages in the antibody-mediated inhibition of axon regeneration. A well characterized antibody passive transfer sciatic nerve crush and transplant models were used to study the anti-ganglioside antibody-mediated inhibition of axon regeneration in wild type and various mutant and transgenic mice with altered expression of specific Fcγ receptors and macrophage/microglia populations. Outcome measures included behavior, electrophysiology, morphometry, immunocytochemistry, quantitative real-time PCR, and western blotting. We demonstrate that the presence of autoantibodies, directed against neuronal/axonal cell surface gangliosides, in the injured mammalian peripheral nerves switch the proregenerative inflammatory environment to growth inhibitory milieu by engaging specific activating Fcγ receptors on recruited monocyte-derived macrophages to cause severe inhibition of axon regeneration. Our data demonstrate that the antibody orchestrated Fcγ receptor-mediated switch in inflammation is one mechanism underlying inhibition of axon regeneration. These findings have clinical implications for nerve repair and recovery in antibody-mediated immune neuropathies. Our results add to the complexity of axon regeneration in injured peripheral and central nervous systems as adverse effects of B cells and autoantibodies on neural injury and repair are increasingly recognized.

  11. Ligand Receptor-Mediated Regulation of Growth in Plants.

    Science.gov (United States)

    Haruta, Miyoshi; Sussman, Michael R

    2017-01-01

    Growth and development of multicellular organisms are coordinately regulated by various signaling pathways involving the communication of inter- and intracellular components. To form the appropriate body patterns, cellular growth and development are modulated by either stimulating or inhibiting these pathways. Hormones and second messengers help to mediate the initiation and/or interaction of the various signaling pathways in all complex multicellular eukaryotes. In plants, hormones include small organic molecules, as well as larger peptides and small proteins, which, as in animals, act as ligands and interact with receptor proteins to trigger rapid biochemical changes and induce the intracellular transcriptional and long-term physiological responses. During the past two decades, the availability of genetic and genomic resources in the model plant species, Arabidopsis thaliana, has greatly helped in the discovery of plant hormone receptors and the components of signal transduction pathways and mechanisms used by these immobile but highly complex organisms. Recently, it has been shown that two of the most important plant hormones, auxin and abscisic acid (ABA), act through signaling pathways that have not yet been recognized in animals. For example, auxins stimulate cell elongation by bringing negatively acting transcriptional repressor proteins to the proteasome to be degraded, thus unleashing the gene expression program required for increasing cell size. The "dormancy" inducing hormone, ABA, binds to soluble receptor proteins and inhibits a specific class of protein phosphatases (PP2C), which activates phosphorylation signaling leading to transcriptional changes needed for the desiccation of the seeds prior to entering dormancy. While these two hormone receptors have no known animal counterparts, there are also many similarities between animal and plant signaling pathways. For example, in plants, the largest single gene family in the genome is the protein kinase

  12. Design and development of hyaluronan-functionalized polybenzofulvene nanoparticles as CD44 receptor mediated drug delivery system

    Science.gov (United States)

    Licciardi, Mariano; Scialabba, Cinzia; Giammona, Gaetano; Paolino, Marco; Razzano, Vincenzo; Grisci, Giorgio; Giuliani, Germano; Makovec, Francesco; Cappelli, Andrea

    2017-06-01

    A tri-component polymer brush (TCPB ), composed of a polybenzofulvene copolymer bearing low molecular weight hyaluronic acid (HA) on the surface of its cylindrical brush-like backbone and oligo-PEG fractions, was employed in the preparation of 350 nm nanostructured drug delivery systems capable of delivering the anticancer drug doxorubicin. The obtained drug delivery systems were characterized on the basis of drug loading and release, dimensions and zeta potential, morphology and in vitro cell activity, and uptake on three different human cell lines, namely the bronchial epithelial 16HBE, the breast adenocarcinoma MCF-7, and the colon cancer HCT116 cells. Finally, the ability of doxorubicin-loaded TCPB nanoparticles (DOXO-TCPB) to be internalized into cancer cells by CD44 receptor mediated uptake was assessed by means of uptake studies in HCT cells. These data were supported by anti-CD44-FITC staining assay. The proposed TCPB nanostructured drug delivery systems have many potential applications in nanomedicine, including cancer targeted drug delivery.

  13. Androgen Receptor-Mediated Escape Mechanisms from Androgen Ablation Therapy

    Science.gov (United States)

    2005-10-01

    pathway independent of phosphatidylinositol 3’-kinase and Akt/protein kinase B. Cancer Res 59:1449-53. 158. Manin M, Baron S, Goossens K, et al. 2002...thyroid hormone-stimulated cell proliferation. Mol Cell Biol 21:6626-39 189. Richard -Parpaillon L, Heligon C, Chesnel F, Boujard D, Philpott A 2002 The IGF

  14. Uptake of 14C-labelled chloroquine and an 125I-labelled chloroquine analogue in some polypeptide hormone producing cell systems

    International Nuclear Information System (INIS)

    Dencker, L.; Lindquist, N.G.; Tjaelve, H.

    1976-01-01

    After the injection of 14 C-labelled chloroquine and the 125 I-labelled chloroquine analogue 4-(3 1 -dimethylaminopropylamino)-7-iodoquinoline [ 125 I]DAPQ into mice, rats and a monkey the distribution of the radioactivity was studied by autoradiographical methods. A high and persistent uptake occurred in some endocrine cell systems, such as the pancreatic islets, the hypophysis, the adrenal medulla and the thyroid (in cells that were probably identical with the parafollicular cells). The melanin-containing tissues were the only ones which showed a higher uptake and retention of radioactivity. The above mentioned endocrine cells and the melanocytes have a common embryological origin and common morphological and cytochemical characteristics. They have been called the APUD (Amine Precursor Uptake and Decarboxylation)-cell series. It is proposed that the polypeptide hormone producing cells and the melanocytes may use a similar mechanism for accumulating chloroquine and (as shown earlier) also some other drugs such as nicotine, alprenolol, local anesthetics and atropine. These drugs however, accumulate stronger within the melanocytes and become bound to the melanin for a long time. The ability to accumulate these drugs may be considered another characteristic of the APUD-cell series. (author)

  15. Thyroid Hormone Effects on Whole-Body Energy Homeostasis and Tissue-Specific Fatty Acid Uptake in Vivo

    NARCIS (Netherlands)

    Klieverik, Lars P.; Coomans, Claudia P.; Endert, Erik; Sauerwein, Hans P.; Havekes, Louis M.; Voshol, Peter J.; Rensen, Patrick C. N.; Romijn, Johannes A.; Kalsbeek, Andries; Fliers, Eric

    2009-01-01

    The effects of thyroid hormone (TH) status on energy metabolism and tissue-specific substrate supply in vivo are incompletely understood. To study the effects of TH status on energy metabolism and tissue-specific fatty acid (FA) fluxes, we used metabolic cages as well as C-14-labeled FA and

  16. Biological functionalization of drug delivery carriers to bypass size restrictions of receptor-mediated endocytosis independently from receptor targeting.

    Science.gov (United States)

    Ansar, Maria; Serrano, Daniel; Papademetriou, Iason; Bhowmick, Tridib Kumar; Muro, Silvia

    2013-12-23

    Targeting of drug carriers to cell-surface receptors involved in endocytosis is commonly used for intracellular drug delivery. However, most endocytic receptors mediate uptake via clathrin or caveolar pathways associated with ≤200-nm vesicles, restricting carrier design. We recently showed that endocytosis mediated by intercellular adhesion molecule 1 (ICAM-1), which differs from clathrin- and caveolae-mediated pathways, allows uptake of nano- and microcarriers in cell culture and in vivo due to recruitment of cellular sphingomyelinases to the plasmalemma. This leads to ceramide generation at carrier binding sites and formation of actin stress-fibers, enabling engulfment and uptake of a wide size-range of carriers. Here we adapted this paradigm to enhance uptake of drug carriers targeted to receptors associated with size-restricted pathways. We coated sphingomyelinase onto model (polystyrene) submicro- and microcarriers targeted to clathrin-associated mannose-6-phosphate receptor. In endothelial cells, this provided ceramide enrichment at the cell surface and actin stress-fiber formation, modifying the uptake pathway and enhancing carrier endocytosis without affecting targeting, endosomal transport, cell-associated degradation, or cell viability. This improvement depended on the carrier size and enzyme dose, and similar results were observed for other receptors (transferrin receptor) and cell types (epithelial cells). This phenomenon also enhanced tissue accumulation of carriers after intravenous injection in mice. Hence, it is possible to maintain targeting toward a selected receptor while bypassing natural size restrictions of its associated endocytic route by functionalization of drug carriers with biological elements mimicking the ICAM-1 pathway. This strategy holds considerable promise to enhance flexibility of design of targeted drug delivery systems.

  17. Effects of interleukin-1 beta on thyrotropin secretion and thyroid hormone uptake in cultured rat anterior pituitary cells

    NARCIS (Netherlands)

    F.W.J.S. Wassen (Frank); E.P.C.M. Moerings (Ellis); H. van Toor (Hans); E.A. de Vrey (Evelyn); G. Hennemann; M.E. Everts (Maria)

    1996-01-01

    textabstractThe effects of interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF alpha) on basal and TRH-induced TSH release, and the effects of IL-1 beta on the uptake of [125I]T3 and [125I]T4 and on nuclear binding of [125I]T3 were examined. Furthermore,

  18. Regulation of C. elegans fat uptake and storage by acyl-CoA synthase-3 is dependent on NR5A family nuclear hormone receptor nhr-25

    DEFF Research Database (Denmark)

    Mullaney, Brendan C; Blind, Raymond D; Lemieux, George A

    2010-01-01

    Acyl-CoA synthases are important for lipid synthesis and breakdown, generation of signaling molecules, and lipid modification of proteins, highlighting the challenge of understanding metabolic pathways within intact organisms. From a C. elegans mutagenesis screen, we found that loss of ACS-3...... mutant phenotypes require the nuclear hormone receptor NHR-25, a key regulator of C. elegans molting. Our findings suggest that ACS-3-derived long-chain fatty acyl-CoAs, perhaps incorporated into complex ligands such as phosphoinositides, modulate NHR-25 function, which in turn regulates an endocrine...... program of lipid uptake and synthesis. These results reveal a link between acyl-CoA synthase function and an NR5A family nuclear receptor in C. elegans....

  19. Cryptococcus neoformans Is Internalized by Receptor-Mediated or ‘Triggered’ Phagocytosis, Dependent on Actin Recruitment

    Science.gov (United States)

    Guerra, Caroline Rezende; Seabra, Sergio Henrique; de Souza, Wanderley; Rozental, Sonia

    2014-01-01

    Cryptococcosis by the encapsulated yeast Cryptococcus neoformans affects mostly immunocompromised individuals and is a frequent neurological complication in AIDS patients. Recent studies support the idea that intracellular survival of Cryptococcus yeast cells is important for the pathogenesis of cryptococcosis. However, the initial steps of Cryptococcus internalization by host cells remain poorly understood. Here, we investigate the mechanism of Cryptococcus neoformans phagocytosis by peritoneal macrophages using confocal and electron microscopy techniques, as well as flow cytometry quantification, evaluating the importance of fungal capsule production and of host cell cytoskeletal elements for fungal phagocytosis. Electron microscopy analyses revealed that capsular and acapsular strains of C. neoformans are internalized by macrophages via both ‘zipper’ (receptor-mediated) and ‘trigger’ (membrane ruffle-dependent) phagocytosis mechanisms. Actin filaments surrounded phagosomes of capsular and acapsular yeasts, and the actin depolymerizing drugs cytochalasin D and latrunculin B inhibited yeast internalization and actin recruitment to the phagosome area. In contrast, nocodazole and paclitaxel, inhibitors of microtubule dynamics decreased internalization but did not prevent actin recruitment to the site of phagocytosis. Our results show that different uptake mechanisms, dependent on both actin and tubulin dynamics occur during yeast internalization by macrophages, and that capsule production does not affect the mode of Cryptococcus uptake by host cells. PMID:24586631

  20. Synthetic peptides corresponding to human follicle-stimulating hormone (hFSH)-beta-(1-15) and hFSH-beta-(51-65) induce uptake of 45Ca++ by liposomes: evidence for calcium-conducting transmembrane channel formation

    Energy Technology Data Exchange (ETDEWEB)

    Grasso, P.; Santa-Coloma, T.A.; Reichert, L.E. Jr. (Department of Biochemistry, Albany Medical College, New York, NY (USA))

    1991-06-01

    We have previously described FSH receptor-mediated influx of 45Ca++ in cultured Sertoli cells from immature rats and receptor-enriched proteoliposomes via activation of voltage-sensitive and voltage-independent calcium channels. We have further shown that this effect of FSH does not require cholera toxin- or pertussis toxin-sensitive guanine nucleotide binding protein or activation of adenylate cyclase. In the present study, we have identified regions of human FSH-beta-subunit which appear to be involved in mediating calcium influx. We screened 11 overlapping peptide amides representing the entire primary structure of hFSH-beta-subunit for their effects on 45Ca++ flux in FSH receptor-enriched proteoliposomes. hFSH-beta-(1-15) and hFSH-beta-(51-65) induced uptake of 45Ca++ in a concentration-related manner. This effect of hFSH-beta-(1-15) and hFSH-beta-(51-65) was also observed in liposomes lacking incorporated FSH receptor. Reducing membrane fluidity by incubating liposomes (containing no receptor) with hFSH-beta-(1-15) or hFSH-beta-(51-65) at temperatures lower than the transition temperatures of their constituent phospholipids resulted in no significant (P greater than 0.05) difference in 45Ca++ uptake. The effectiveness of the calcium ionophore A23187, however, was abolished. Ruthenium red, a voltage-independent calcium channel antagonist, was able to completely block uptake of 45Ca++ induced by hFSH-beta-(1-15) and hFSH-beta-(51-65) whereas nifedipine, a calcium channel blocker specific for L-type voltage-sensitive calcium channels, was without effect. These results suggest that in addition to its effect on voltage-sensitive calcium channel activity, interaction of FSH with its receptor may induce formation of transmembrane aqueous channels which also facilitate influx of extracellular calcium.

  1. The absorption and uptake of recombinant human follicle-stimulating hormone through vaginal subcutaneous injections - a pharmacokinetic study

    Science.gov (United States)

    Hsu, Chao-Chin; Kuo, Hsin-Chih; Hsu, Chao-Tien; Gu, Qing

    2009-01-01

    Background Follicle stimulating hormone (FSH) has been routinely used for ovulation induction. Because of rapid clearance of the hormone, FSH is commonly administered by daily intramuscular or subcutaneous injections in in-vitro fertilization (IVF). To reduce the number of visits to the clinic, an intermittent vaginal injection of rhFSH every 3 days employing the concepts of mesotherapy and uterine first-pass effect was invented and has successfully been applied in women receiving IVF treatment. This study was designed to monitor the pharmacokinetic pattern of rhFSH administered vaginally. Methods Twelve healthy women with regular ovulatory cycles were recruited. All volunteers received gonadotrophin-releasing hormone agonist to suppress pituitary function and were assigned to receive single dose recombinant human FSH (rhFSH, Puregon 300) either using conventional abdominal subcutaneous injection or vaginal subcutaneous injection in a randomized cross-over study. Serum samples were collected at pre- scheduled time intervals after injections of rhFSH to determine immunoreactive FSH levels. Pharmacokinetic parameters characterizing rate [maximal plasma concentrations (Cmax) and time of maximal plasma concentrations (tmax)] and extent [area under the plasma concentration-time curve (AUC) and clearance] of absorption of rhFSH were compared. Results Vaginal injection of rhFSH was well tolerated and no drug-related adverse reaction was noted. Our analysis revealed that tmax was significantly earlier (mean 6.67 versus 13.33 hours) and Cmax was significantly higher (mean 17.77 versus 13.96 IU/L) in vaginal versus abdominal injections. The AUC0-∞ was 1640 versus 1134 IU·hour/L in vaginal and abdominal injections, respectively. Smaller plasma elimination rate constant (0.011 versus 0.016 hour-1), longer mean residence time (106.58 versus 70.47 hours), and slower total body clearance (292.2 versus 400.1 mL/hour) were also found in vaginal injection. Conclusion The vaginal

  2. The absorption and uptake of recombinant human follicle-stimulating hormone through vaginal subcutaneous injections - a pharmacokinetic study

    Directory of Open Access Journals (Sweden)

    Kuo Hsin-Chih

    2009-10-01

    Full Text Available Abstract Background Follicle stimulating hormone (FSH has been routinely used for ovulation induction. Because of rapid clearance of the hormone, FSH is commonly administered by daily intramuscular or subcutaneous injections in in-vitro fertilization (IVF. To reduce the number of visits to the clinic, an intermittent vaginal injection of rhFSH every 3 days employing the concepts of mesotherapy and uterine first-pass effect was invented and has successfully been applied in women receiving IVF treatment. This study was designed to monitor the pharmacokinetic pattern of rhFSH administered vaginally. Methods Twelve healthy women with regular ovulatory cycles were recruited. All volunteers received gonadotrophin-releasing hormone agonist to suppress pituitary function and were assigned to receive single dose recombinant human FSH (rhFSH, Puregon 300 either using conventional abdominal subcutaneous injection or vaginal subcutaneous injection in a randomized cross-over study. Serum samples were collected at pre- scheduled time intervals after injections of rhFSH to determine immunoreactive FSH levels. Pharmacokinetic parameters characterizing rate [maximal plasma concentrations (Cmax and time of maximal plasma concentrations (tmax] and extent [area under the plasma concentration-time curve (AUC and clearance] of absorption of rhFSH were compared. Results Vaginal injection of rhFSH was well tolerated and no drug-related adverse reaction was noted. Our analysis revealed that tmax was significantly earlier (mean 6.67 versus 13.33 hours and Cmax was significantly higher (mean 17.77 versus 13.96 IU/L in vaginal versus abdominal injections. The AUC0-∞ was 1640 versus 1134 IU·hour/L in vaginal and abdominal injections, respectively. Smaller plasma elimination rate constant (0.011 versus 0.016 hour-1, longer mean residence time (106.58 versus 70.47 hours, and slower total body clearance (292.2 versus 400.1 mL/hour were also found in vaginal injection

  3. Histamine H2 Receptor-Mediated Suppression of Intestinal Inflammation by Probiotic Lactobacillus reuteri.

    Science.gov (United States)

    Gao, Chunxu; Major, Angela; Rendon, David; Lugo, Monica; Jackson, Vanessa; Shi, Zhongcheng; Mori-Akiyama, Yuko; Versalovic, James

    2015-12-15

    -mediated suppression of colonic inflammation. The effective combination of diet, gut bacteria, and host receptor-mediated signaling may result in opportunities for therapeutic microbiology and provide clues for discovery and development of next-generation probiotics. Copyright © 2015 Gao et al.

  4. Role of receptor-mediated endocytosis in the antiangiogenic effects of human T lymphoblastic cell-derived microparticles.

    Science.gov (United States)

    Yang, Chun; Xiong, Wei; Qiu, Qian; Shao, Zhuo; Shao, Zuo; Hamel, David; Tahiri, Houda; Leclair, Grégoire; Lachapelle, Pierre; Chemtob, Sylvain; Hardy, Pierre

    2012-04-15

    Microparticles possess therapeutic potential regarding angiogenesis. We have demonstrated the contribution of apoptotic human CEM T lymphocyte-derived microparticles (LMPs) as inhibitors of angiogenic responses in animal models of inflammation and tumor growth. In the present study, we characterized the antivascular endothelial growth factor (VEGF) effects of LMPs on pathological angiogenesis in an animal model of oxygen-induced retinopathy and explored the role of receptor-mediated endocytosis in the effects of LMPs on human retinal endothelial cells (HRECs). LMPs dramatically inhibited cell growth of HRECs, suppressed VEGF-induced cell migration in vitro experiments, and attenuated VEGF-induced retinal vascular leakage in vivo. Intravitreal injections of fluorescently labeled LMPs revealed accumulation of LMPs in retinal tissue, with more than 60% reductions of the vascular density in retinas of rats with oxygen-induced neovascularization. LMP uptake experiments demonstrated that the interaction between LMPs and HRECs is dependent on temperature. In addition, endocytosis is partially dependent on extracellular calcium. RNAi-mediated knockdown of low-density lipoprotein receptor (LDLR) reduced the uptake of LMPs and attenuated the inhibitory effects of LMPs on VEGF-A protein expression and HRECs cell growth. Intravitreal injection of lentivirus-mediated RNA interference reduced LDLR protein expression in retina by 53% and significantly blocked the antiangiogenic effects of LMPs on pathological vascularization. In summary, the potent antiangiogenic LMPs lead to a significant reduction of pathological retinal angiogenesis through modulation of VEGF signaling, whereas LDLR-mediated endocytosis plays a partial, but pivotal, role in the uptake of LMPs in HRECs.

  5. Differential modulation of expression of nuclear receptor mediated genes by tris(2-butoxyethyl) phosphate (TBOEP) on early life stages of zebrafish (Danio rerio)

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Zhiyuan, E-mail: zhiyuan_nju@163.com [State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, Jiangsu 210023 (China); Yu, Yijun, E-mail: yjun.yu@gmail.com [State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, Jiangsu 210023 (China); Tang, Song [School of Environment and Sustainability, University of Saskatchewan, Saskatoon, SK S7N 5B3 (Canada); Liu, Hongling, E-mail: hlliu@nju.edu.cn [State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, Jiangsu 210023 (China); Su, Guanyong; Xie, Yuwei [State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, Jiangsu 210023 (China); Giesy, John P. [State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, Jiangsu 210023 (China); Toxicology Centre, University of Saskatchewan, Saskatoon, SK S7N 5B3 (Canada); Department of Veterinary Biomedical Sciences, University of Saskatchewan, Saskatoon, SK S7N 5B3 (Canada); Department of Biology and Chemistry, City University of Hong Kong, Kowloon, Hong Kong Special Administrative Region (Hong Kong); Hecker, Markus [School of Environment and Sustainability, University of Saskatchewan, Saskatoon, SK S7N 5B3 (Canada); Toxicology Centre, University of Saskatchewan, Saskatoon, SK S7N 5B3 (Canada); Yu, Hongxia [State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, Jiangsu 210023 (China)

    2015-12-15

    Highlights: • Effects of TBOEP on expression of genes of several nuclear hormone receptors and their relationship with adverse effect pathways in zebrafish. • TBOEP was neither an agonist nor antagonist of AR or AhR as determined by use of in vitro mammalian cell-based receptor transactivation assays. • Modulation of ER- and MR-dependent pathways allowed for development of feasible receptor-mediated, critical mechanisms of toxic action. - Abstract: As one substitute for phased-out brominated flame retardants (BFRs), tris(2-butoxyethyl) phosphate (TBOEP) is frequently detected in aquatic organisms. However, knowledge about endocrine disrupting mechanisms associated with nuclear receptors caused by TBOEP remained restricted to results from in vitro studies with mammalian cells. In the study, results of which are presented here, embryos/larvae of zebrafish (Danio rerio) were exposed to 0.02, 0.1 or 0.5 μM TBOEP to investigate expression of genes under control of several nuclear hormone receptors (estrogen receptors (ERs), androgen receptor (AR), thyroid hormone receptor alpha (TRα), mineralocorticoid receptor (MR), glucocorticoid receptor (GR), aryl hydrocarbon (AhR), peroxisome proliferator-activated receptor alpha (PPARα), and pregnane × receptor (P × R)) pathways at 120 hpf. Exposure to 0.5 μM TBOEP significantly (p < 0.05, one-way analysis of variance) up-regulated expression of estrogen receptors (ERs, er1, er2a, and er2b) genes and ER-associated genes (vtg4, vtg5, pgr, ncor, and ncoa3), indicating TBOEP modulates the ER pathway. In contrast, expression of most genes (mr, 11βhsd, ube2i,and adrb2b) associated with the mineralocorticoid receptor (MR) pathway were significantly down-regulated. Furthermore, in vitro mammalian cell-based (MDA-kb2 and H4IIE-luc) receptor transactivation assays, were also conducted to investigate possible agonistic or antagonistic effects on AR- and AhR-mediated pathways. In mammalian cells, none of these pathways were

  6. Environmental phthalate monoesters activate pregnane X receptor-mediated transcription

    International Nuclear Information System (INIS)

    Hurst, Christopher H.; Waxman, David J.

    2004-01-01

    Phthalate esters, widely used as plasticizers in the manufacture of products made of polyvinyl chloride, induce reproductive and developmental toxicities in rodents. The mechanism that underlies these effects of phthalate exposure, including the potential role of members of the nuclear receptor superfamily, is not known. The present study investigates the effects of phthalates on the pregnane X receptor (PXR), which mediates the induction of enzymes involved in steroid metabolism and xenobiotic detoxification. The ability of phthalate monoesters to activate PXR-mediated transcription was assayed in a HepG2 cell reporter assay following transfection with mouse PXR (mPXR), human PXR (hPXR), or the hPXR allelic variants V140M, D163G, and A370T. Mono-2-ethylhexyl phthalate (MEHP) increased the transcriptional activity of both mPXR and hPXR (5- and 15-fold, respectively) with EC 50 values of 7-8 μM. mPXR and hPXR were also activated by monobenzyl phthalate (MBzP, up to 5- to 6-fold) but were unresponsive to monomethyl phthalate and mono-n-butyl phthalate (M(n)BP) at the highest concentrations tested (300 μM). hPXR-V140M and hPXR-A370T exhibited patterns of phthalate responses similar to the wild-type receptor. By contrast, hPXR-D163G was unresponsive to all phthalate monoesters tested. Further studies revealed that hPXR-D163G did respond to rifampicin, but required approximately 40-fold higher concentrations than wild-type receptor, suggesting that the ligand-binding domain D163G variant has impaired ligand-binding activity. The responsiveness of PXR to activation by phthalate monoesters demonstrated here suggests that these ubiquitous environmental chemicals may, in part, exhibit their endocrine disruptor activities by altering PXR-regulated steroid hormone metabolism with potential adverse health effects in exposed individuals

  7. Effects of caloric deprivation on thyroid hormone tissue uptake and generation of low-T3 syndrome

    International Nuclear Information System (INIS)

    van der Heyden, J.T.M.; Docter, R.; van Toor, H.; Wilson, J.H.P.; Hennemann, G.; Krenning, E.P.

    1986-01-01

    Changes in thyroid hormone metabolism in the low-3,5,3'-triiodothyronine (T 3 ) syndrome cannot be fully explained in all conditions by a decrease in 5'-deiodinase activity. Recent observations showed that in rat hepatocytes iodothyronines are taken up by an active transport mechanism. To investigate whether regulation, i.e., inhibition of active transmembraneous transport for iodothyronines in humans may contribute to the generation of the low-T 3 syndrome, tracer thyroxine (T 4 ) and T 3 kinetic studies were performed in 10 obese subjects before and after 7 days on a 240 kcal diet. Kinetics analyses were performed according to a three-pool model of distribution and metabolism for both T 4 and T 3 . For T 4 kinetics, during caloric deprivation serum total T 4 and plasma pool did not change and production rate and metabolic clearance rate (MCR) were significantly lower. Despite a significantly higher serum free T 4 , the mass transfer rate to the rapidly equilibrating pool (REP) and the slowly equilibrating pool (SEP) diminished significantly, leading to smaller tissue pools. For T 3 kinetics, both serum total T 3 , free T 3 , plasma pool, and production rate diminished significantly, while MCR remained unchanged. These changes cannot be fully explained by a similar decrease of serum free T 3 (only 25%), indicating a diminished transport efficiency for T 3 . In conclusion, during caloric restriction, transport of T 4 and T 3 into tissues is diminished, and this phenomenon is much more pronounced for T 4 transport per se may contribute to low-T 3 production and low-T 3 serum levels due to less substrate (i.e., T 4 ) availability in tissues

  8. Ruthenium complexes with phenylterpyridine derivatives target cell membrane and trigger death receptors-mediated apoptosis in cancer cells.

    Science.gov (United States)

    Deng, Zhiqin; Gao, Pan; Yu, Lianling; Ma, Bin; You, Yuanyuan; Chan, Leung; Mei, Chaoming; Chen, Tianfeng

    2017-06-01

    Elucidation of the communication between metal complexes and cell membrane may provide useful information for rational design of metal-based anticancer drugs. Herein we synthesized a novel class of ruthenium (Ru) complexes containing phtpy derivatives (phtpy = phenylterpyridine), analyzed their structure-activity relationship and revealed their action mechanisms. The result showed that, the increase in the planarity of hydrophobic Ru complexes significantly enhanced their lipophilicity and cellular uptake. Meanwhile, the introduction of nitro group effectively improved their anticancer efficacy. Further mechanism studies revealed that, complex (2c), firstly accumulated on cell membrane and interacted with death receptors to activate extrinsic apoptosis signaling pathway. The complex was then transported into cell cytoplasm through transferrin receptor-mediated endocytosis. Most of the intracellular 2c accumulated in cell plasma, decreasing the level of cellular ROS, inducing the activation of caspase-9 and thus intensifying the apoptosis. At the same time, the residual 2c can translocate into cell nucleus to interact with DNA, induce DNA damage, activate p53 pathway and enhance apoptosis. Comparing with cisplatin, 2c possesses prolonged circulation time in blood, comparable antitumor ability and importantly, much lower toxicity in vivo. Taken together, this study uncovers the role of membrane receptors in the anticancer actions of Ru complexes, and provides fundamental information for rational design of membrane receptor targeting anticancer drugs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Upregulation of endothelin ETB receptor-mediated vasoconstriction in rat coronary artery after organ culture

    DEFF Research Database (Denmark)

    Eskesen, Karen; Edvinsson, Lars

    2006-01-01

    The aim of this study was to examine if endothelin ET(B) receptor-mediated contraction occurred in isolated segments of rat coronary arteries during organ culture. Presence of contractile endothelin ET(B) receptors was studied by measuring the change in isometric tension in rings of left anterior......(+)-solution was not modified after 1 day in culture medium. The experiments indicate that organ culture of rat coronary arteries upregulate endothelin ET(B) receptor-mediated contraction by inducing synthesis of new protein....... descending coronary arteries isolated from hearts of rats as response to application of the selective endothelin ET(B) receptor agonist, Sarafotoxin 6c and endothelin-1. In segments cultured 1 day in serum free Dulbecco's Modified Eagle's Medium, Sarafotoxin 6c induced a concentration dependent contraction...

  10. THIP, a hypnotic and antinociceptive drug, enhances a tonic GABAA receptor mediated conductance in mouse neocortex

    DEFF Research Database (Denmark)

    Drasbek, Kim Ryun; Jensen, Kimmo

    2006-01-01

    its cellular actions in the neocortex are uncertain, we studied the effects of THIP on neurons in slices of frontoparietal neocortex of 13- to 19-day-old (P13-19) mice. Using whole-cell patch-clamp recordings, we found that the clinically relevant THIP concentration of 1 μM induced a robust tonic GABA...... suggest that THIP activates an extrasynaptic GABA(A) receptor-mediated conductance in the neocortex, which may alter the cortical network activity....

  11. The Influence of Receptor-Mediated Interactions on Reaction-Diffusion Mechanisms of Cellular Self-organisation

    KAUST Repository

    Klika, Vá clav; Baker, Ruth E.; Headon, Denis; Gaffney, Eamonn A.

    2011-01-01

    formation, motivating numerous theoretical and experimental studies, though its verification at the molecular level in biological systems has remained elusive. In this work, we consider the influence of receptor-mediated dynamics within the framework

  12. Onset of lipoprotein-supported steroidogenesis in differentiating granulosa cells of rats: cellular events involved in mediating FSH-enhanced uptake of low-density lipoproteins

    International Nuclear Information System (INIS)

    Foster, J.D.

    1987-01-01

    Luteal cells use lipoproteins as the main source of cholesterol in steroidogenesis. However, little is known about the mechanisms underlying hormonal control of lipoprotein uptake. Thus, the authors tested the hypothesis that FSH and androgens regulate low density lipoprotein (LDL)-supported steroidogenesis in maturing granulosa cells by affecting receptor-mediated endocytosis of LDL at a cellular level. For this, immature ovarian granulosa cells were cultured with or without hormones, compactin (de novo synthesis inhibitor), or unlabeled or labeled ( 125 I or gold particles) LDL. Nonhormone-treated cultures produced little progestin; FSH and FSH/androstenedione stimulated steroid secretion. Progestin production by hormone-, but not nonhormone-, treated cultures was decreased by compactin, suggesting that de novo synthesis provided sterol for steroidogenesis. EM quantitation of cells exposed to gold-LDL at 37 0 C revealed that, compared to nonhormone-treated cells, FSH-treated cells (1) bound and internalized more gold-LDL, (2) had a smaller percentage of gold-LDL at their surfaces, (3) displayed a faster apparent rate of LDL internalization and delivery to lysosomes, and (4) contained more gold-labeled lysosomes. Data from biochemical studies in which 125 I-LDL was used supported the morphological findings. In conclusion, this study demonstrates that FSH has important effects at the cellular level on LDL uptake, which seem to underlie the striking increase in progestin production accompanying granulosa cell differentiation

  13. Neuropeptide Y restores non-receptor-mediated vasoconstrictive action in superior mesenteric arteries in portal hypertension.

    Science.gov (United States)

    Hartl, Johannes; Dietrich, Peter; Moleda, Lukas; Müller-Schilling, Martina; Wiest, Reiner

    2015-12-01

    Vascular hyporeactivity to vasoconstrictors contributes to splanchnic arterial vasodilatation and hemodynamic dysregulation in portal hypertension. Neuropeptide Y (NPY), a sympathetic cotransmitter, has been shown to improve adrenergic vascular contractility in portal hypertensive rats and markedly attenuate hyperdynamic circulation. To further characterize the NPY-effects in portal hypertension, we investigated its role for non-receptor-mediated vasoconstriction in the superior mesenteric artery (SMA) of portal vein ligated (PVL) and sham-operated rats. Ex vivo SMA perfusion of PVL and sham rats was used to analyse the effects of NPY on pressure response to non-receptor-mediated vasoconstriction. Dose-response curves to KCl (30-300 mM) were used to bypass G protein-coupled receptor mechanisms. Potential involvement of the cyclooxygenase-pathway was tested by non-selective cyclooxygenase-inhibition using indomethacin. KCl-induced vascular contractility but not vascular sensitivity was significantly attenuated in PVL rats as compared with sham rats. Administration of NPY resulted in an augmentation of KCl-evoked vascular sensitivity being not different between study groups. However, KCl-induced vascular contractility was markedly more enhanced in PVL rats, thus, vascular response was no more significantly different between PVL and sham rats after addition of NPY. Administration of indomethacin abolished the NPY-induced enhancement of vasoconstriction. Receptor-independent vascular contractility is impaired in mesenteric arteries in portal hypertension. NPY improves non-receptor mediated mesenteric vasoconstriction more effective in portal hypertension than in healthy conditions correcting splanchnic vascular hyporesponsiveness. This beneficial vasoactive action of NPY adds to its well known more pronounced effects on adrenergic vasoconstriction in portal hypertension making it a promising therapeutic agent in portal hypertension. © 2015 John Wiley & Sons A

  14. Receptor-Mediated Drug Delivery to Macrophages in Chemotherapy of Leishmaniasis

    Science.gov (United States)

    Mukhopadhyay, Amitabha; Chaudhuri, Gautam; Arora, Sunil K.; Sehgal, Shobha; Basu, Sandip K.

    1989-05-01

    Methotrexate coupled to maleylated bovine serum albumin was taken up efficiently through the ``scavenger'' receptors present on macrophages and led to selective killing of intracellular Leishmania mexicana amazonensis amastigotes in cultured hamster peritoneal macrophages. The drug conjugate was nearly 100 times as effective as free methotrexate in eliminating the intracellular parasites. Furthermore, in a model of experimental cutaneous leishmaniasis in hamsters, the drug conjugate brought about more than 90% reduction in the size of footpad lesions within 11 days. In contrast, the free drug at a similar concentration did not significantly affect lesion size. These studies demonstrate the potential of receptor-mediated drug delivery in the therapy of macrophage-associated diseases.

  15. Melanocortin MC(4) receptor-mediated feeding and grooming in rodents.

    Science.gov (United States)

    Mul, Joram D; Spruijt, Berry M; Brakkee, Jan H; Adan, Roger A H

    2013-11-05

    Decades ago it was recognized that the pharmacological profile of melanocortin ligands that stimulated grooming behavior in rats was strikingly similar to that of Xenopus laevis melanophore pigment dispersion. After cloning of the melanocortin MC1 receptor, expressed in melanocytes, and the melanocortin MC4 receptor, expressed mainly in brain, the pharmacological profiles of these receptors appeared to be very similar and it was demonstrated that these receptors mediate melanocortin-induced pigmentation and grooming respectively. Grooming is a low priority behavior that is concerned with care of body surface. Activation of central melanocortin MC4 receptors is also associated with meal termination, and continued postprandial stimulation of melanocortin MC4 receptors may stimulate natural postprandial grooming behavior as part of the behavioral satiety sequence. Indeed, melanocortins fail to suppress food intake or induce grooming behavior in melanocortin MC4 receptor-deficient rats. This review will focus on how melanocortins affect grooming behavior through the melanocortin MC4 receptor, and how melanocortin MC4 receptors mediate feeding behavior. This review also illustrates how melanocortins were the most likely candidates to mediate grooming and feeding based on the natural behaviors they induced. Copyright © 2013 Elsevier B.V. All rights reserved.

  16. Thyroid hormone stimulated glucose uptake in human mononuclear blood cells from normal persons and from patients with non-insulin-dependent diabetes mellitus

    DEFF Research Database (Denmark)

    Kvetny, J; Matzen, L

    1989-01-01

    Thyroxine and T3 induced oxygen consumption and glucose uptake were studied in vitro in mononuclear blood cells isolated from patients with non-insulin-dependent diabetes mellitus (NIDDM) and from non-diabetic control persons. Cellular oxygen consumption and glucose uptake were promptly increased...

  17. Receptor-mediated photo-cytotoxicity: synthesis of a photoactivatable psoralen derivative conjugated to insulin.

    Science.gov (United States)

    Gasparro, F P; Knobler, R M; Yemul, S S; Bisaccia, E; Edelson, R L

    1986-12-15

    4'-Aminomethyl-4,5',8-trimethylpsoralen has been chemically conjugated to insulin using a carbodiimide derivative. The psoralen moiety retains its photochemical reactivity as evidenced by its ability to crosslink DNA after exposure to long wavelength ultraviolet light (UVA, 320-400 nm). This chimeric molecule has been used to selectively kill a population of lymphocytes whose expression of insulin receptors has been stimulated with phytohemagglutinin. Insulin carries the psoralen into the cell via receptor-mediated endocytosis, where it is subsequently activated by exposure to UVA light. The UVA induced activity of AMT-insulin can be blocked by the presence of native insulin. The viability of unstimulated lymphocytes was not affected by AMT-insulin and UVA light. The hybrid insulin-psoralen molecule may be a prototype for a family of phototoxic drugs which can be selectively delivered to subsets of lymphocytes.

  18. Platelet alpha-2 adrenergic receptor-mediated phosphoinositide responses in endogenous depression

    International Nuclear Information System (INIS)

    Mori, Hideki; Koyama, Tsukasa; Yamashita, Itaru

    1991-01-01

    We have previously indicated that epinephrine stimulates phosphoinositide (PI) hydrolysis by activating alpha-2 adrenergic receptors in human platelets. This method involves the measurement of the accumulation of [ 3 H]-inositol-1-phosphate (IP-1) as an index of Pl hydrolysis; lithium is added to inhibit the metabolism of IP-1, thus giving an enhanced signal. In the present study, we assessed the platelet alpha-2 adrenergic receptor-mediated PI responses in samples from 15 unmedicated patients with endogenous depression and 15 age- and sex-matched control subjects. The responses to epinephrine in the depressed patients were significantly higher than those of the controls, whereas the basal values did not differ significantly. These results support the hypothesis that platelet alpha-2 adrenergic receptors may be supersensitive in patients with endogenous depression

  19. Bicarbonate Contributes to GABAA Receptor-Mediated Neuronal Excitation in Surgically-Resected Human Hypothalamic Hamartomas

    Science.gov (United States)

    Do-Young, Kim; Fenoglio, Kristina A.; Kerrigan, John F.; Rho, Jong M.

    2009-01-01

    SUMMARY The role of bicarbonate (HCO3-) in GABAA receptor-mediated depolarization of human hypothalamic hamartoma (HH) neurons was investigated using cellular electrophysiological and calcium imaging techniques. Activation of GABAA receptors with muscimol (30 μM) provoked neuronal excitation in over 70% of large (18-22 μM) HH neurons in HCO3- buffer. Subsequent perfusion of HCO3--free HEPES buffer produced partial suppression of muscimol-induced excitation. Additionally, 53% of large HH neurons under HCO3--free conditions exhibited reduced intracellular calcium accumulation by muscimol. These results suggest that HCO3- efflux through GABAA receptors on a subpopulation of large HH neurons may contribute to membrane depolarization and subsequent activation of L-type calcium channels. PMID:19022626

  20. Gelidium amansii promotes dendritic spine morphology and synaptogenesis, and modulates NMDA receptor-mediated postsynaptic current.

    Science.gov (United States)

    Hannan, Md Abdul; Mohibbullah, Md; Hong, Yong-Ki; Nam, Joo Hyun; Moon, Il Soo

    2014-01-01

    Neurotrophic factors are essential for the differentiation and maturation of developing neurons as well as providing survival support to the mature neurons. Moreover, therapeutically neurotrophic factors are promising to reconstruct partially damaged neuronal networks in neurodegenerative diseases. In the previous study, we reported that the ethanol extract of an edible marine alga, Gelidium amansii (GAE) had shown promising effects in the development and maturation of both axon and dendrites of hippocampal neurons. Here, we demonstrate that in primary culture of hippocampal neurons (1) GAE promotes a significant increase in the number of filopodia and dendritic spines; (2) promotes synaptogenesis; (3) enhances N-methyl-D-aspartic acid (NMDA) receptor recruitment; and (4) modulates NMDA-receptor-mediated postsynaptic current. Taken together these findings that GAE might be involved in both morphological and functional maturation of neurons suggest the possibility that GAE may constitute a promising candidate for novel compounds for the prevention and treatment of neurodegenerative diseases.

  1. Cellular uptake of lipoproteins and persistent organic compounds-An update and new data

    International Nuclear Information System (INIS)

    Hjelmborg, Philip Sebastian; Andreassen, Thomas Kjaergaard; Bonefeld-Jorgensen, Eva Cecilie

    2008-01-01

    There are a number of interactions related to the transport of lipophilic xenobiotic compounds in the blood stream of mammals. This paper will focus on the interactions between lipoproteins and persistent organic pollutants (POPs) and how these particles are taken up by cells. A number of POPs including the pesticide p,p'-dichlorodiphenyltrichloroethane (DDT), and especially its metabolite p,p'-dichlorodiphenyldichloroethene (DDE), interacts with nuclear hormone receptors causing these to malfunction, which in turn results in a range of deleterious health effects in humans. The aim of the present study was to determine the role of lipoprotein receptors in mouse embryonic fibroblast (MEF) cells in conjunction with uptake of DDT-lipoprotein complexes from supplemented media in vitro. Uptake of DDT by MEF cells was investigated using MEF1 cells carrying the receptors low-density lipoprotein receptor-related protein (LRP) and low-density lipoprotein receptor (LDLR) present and MEF4 cells with no LRP and LDLR expression. Cells were incubated together with the complex of low-density lipoproteins (LDL) and [ 14 C]DDT. The receptor function was further evaluated by adding the 40 kDa receptor-associated protein (RAP) which blocks receptor activity. The results showed that [ 14 C]DDT uptake was decreasing when the LDL concentration was increasing. There was no strong evidence for a receptor-mediated uptake of the [ 14 C]DDT-lipoprotein complex. To conclude, DDT travels in the blood stream and can cross cell membranes while being transported as a DDT-lipoprotein complex. The lipoproteins do not need receptors to cross cell membranes since passive diffusion constitutes a major passageway

  2. Monocyte CD64 or CD89 targeting by surfactant protein D/anti-Fc receptor mediates bacterial uptake.

    NARCIS (Netherlands)

    Tacken, P.J.; Batenburg, J.J.

    2006-01-01

    We recently showed that a chimeric protein, consisting of a recombinant fragment of human surfactant protein D (rfSP-D) coupled to a Fab' fragment directed against the human Fcalpha receptor (CD89), effectively targets pathogens recognized by SP-D to human neutrophils. The present study evaluates

  3. Protein expression from exogenous mRNA: uptake by receptor-mediated endocytosis and trafficking via the lysosomal pathway.

    NARCIS (Netherlands)

    Lorenz, C.; Fotin-Mleczek, M.; Roth, G.; Becker, C.; Dam, T.C.; Verdurmen, W.P.R.; Brock, R.E.; Probst, J.; Schlake, T.

    2011-01-01

    Insertional mutagenesis and the inherent risk of malignancy compromise the clinical use of DNA-based therapies. Being a transient copy of genetic material, mRNA is a safe alternative, overcoming this limitation. As a prerequisite for the development of efficient mRNA-based therapies, we investigated

  4. Genetically designed biomolecular capping system for mesoporous silica nanoparticles enables receptor-mediated cell uptake and controlled drug release

    Czech Academy of Sciences Publication Activity Database

    Datz, S.; Argyo, C.; Gattner, M.; Weiss, V.; Brunner, K.; Bretzler, J.; von Schirnding, C.; Torrano, A. A.; Spada, F.; Vrábel, Milan; Engelke, H.; Bräuchle, C.; Carell, T.; Bein, T.

    2016-01-01

    Roč. 8, č. 15 (2016), s. 8101-8110 ISSN 2040-3364 Institutional support: RVO:61388963 Keywords : responsive controlled release * Diels-Alder reactions * human carbonic anhydrase Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 7.367, year: 2016 http://pubs.rsc.org/en/content/articlehtml/2016/nr/c5nr08163g

  5. The role of receptor-mediated T-cells activation disorders in pulmonary tuberculosis

    Directory of Open Access Journals (Sweden)

    Irina E. Esimova

    2017-01-01

    Full Text Available Aim. To analyze the peculiarities and mechanisms of receptor-mediated T-lymphocytes disorders in different clinical forms of pulmonary tuberculosis.Materials and мethods. The study involved 116 patients with first diagnosed infiltrative and disseminated drug-sensitive and drug-resistant pulmonary tuberculosis. The key stages in receptor-mediated activation of T-lymphocytes, isolated from blood, after their CD3/CD28-induction in vitro with addition of intracellular transport blocker were analyzed. Their immunotyping was carried out with the method of two- and threecolor flow cytofluorometry. The obtained results were statistically analyzed.Results. The breach of extracellular and intracellular stages of T-lymphocytes activation, shown by reduction in total number of CD3- and CD28-positive cells, and CD3+CD28+IL2+, CD3+CD28+IL2–, CD3+NF-kB+, CD3+NFAT2+ lymphocytes, and increase in number of CD3+CTLA4+ cells, was identified with most of their manifestations in disseminated drug-resistant pulmonary tuberculosis. It was shown that the content of CD3+AP-1+ lymphocytes is variable in drug-resistant pulmonary tuberculosis: it increases in the infiltrative form and decreases in the disseminated form.Conclusion. The results showed different mechanisms leading to a deficiency of IL-2-positive lymphocytes and T-lymphocytopenia: from “functional reserve” exhaustion of T-cells in drug-sensitive pulmonary tuberculosis to immunosuppression under the influence of suppressive cytokines (in case of the infiltrative form and inhibitory protein CTLA4 (in case of the disseminated form in drug-resistant pulmonary tuberculosis. 

  6. Effects of sarcosine and N, N-dimethylglycine on NMDA receptor-mediated excitatory field potentials.

    Science.gov (United States)

    Lee, Mei-Yi; Lin, Yi-Ruu; Tu, Yi-Shu; Tseng, Yufeng Jane; Chan, Ming-Huan; Chen, Hwei-Hsien

    2017-02-28

    Sarcosine, a glycine transporter type 1 inhibitor and an N-methyl-D-aspartate (NMDA) receptor co-agonist at the glycine binding site, potentiates NMDA receptor function. Structurally similar to sarcosine, N,N-dimethylglycine (DMG) is also N-methyl glycine-derivative amino acid and commonly used as a dietary supplement. The present study compared the effects of sarcosine and DMG on NMDA receptor-mediated excitatory field potentials (EFPs) in mouse medial prefrontal cortex brain slices using a multi-electrode array system. Glycine, sarcosine and DMG alone did not alter the NMDA receptor-mediated EFPs, but in combination with glutamate, glycine and its N-methyl derivatives significantly increased the frequency and amplitude of EFPs. The enhancing effects of glycine analogs in combination with glutamate on EFPs were remarkably reduced by the glycine binding site antagonist 7-chlorokynurenate (7-CK). However, DMG, but not sarcosine, reduced the frequency and amplitude of EFPs elicited by co-application of glutamate plus glycine. D-cycloserine, a partial agonist at the glycine binding site on NMDA receptors, affected EFPs in a similar manner to DMG. Furthermore, DMG, but not sarcosine, reduced the frequencies and amplitudes of EFPs elicited by glutamate plus D-serine, another endogenous ligand for glycine binding site. These findings suggest that sarcosine acts as a full agonist, yet DMG is a partial agonist at glycine binding site of NMDA receptors. The molecular docking analysis indicated that the interactions of glycine, sarcosine, and DMG to NMDA receptors are highly similar, supporting that the glycine binding site of NMDA receptors is a critical target site for sarcosine and DMG.

  7. Receptor-mediated endocytosis and intracellular trafficking of insulin and low-density lipoprotein by retinal vascular endothelial cells.

    Science.gov (United States)

    Stitt, A W; Anderson, H R; Gardiner, T A; Bailie, J R; Archer, D B

    1994-08-01

    The authors investigated the receptor-mediated endocytosis (RME) and intracellular trafficking of insulin and low-density lipoprotein (LDL) in cultured retinal vascular endothelial cells (RVECs). Low-density lipoprotein and insulin were conjugated to 10 nm colloidal gold, and these ligands were added to cultured bovine RVECs for 20 minutes at 4 degrees C. The cultures were then warmed to 37 degrees C and fixed after incubation times between 30 seconds and 1 hour. Control cells were incubated with unconjugated gold colloid at times and concentrations similar to those of the ligands. Additional control cells were exposed to several concentrations of anti-insulin receptor antibody or a saturating solution of unconjugated insulin before incubation with gold insulin. Using transmission electron microscopy, insulin gold and LDL gold were both observed at various stages of RME. Insulin-gold particles were first seen to bind to the apical plasma membrane (PM) before clustering in clathrin-coated pits and internalization in coated vesicles. Gold was later visualized in uncoated cytoplasmic vesicles, corresponding to early endosomes and multivesicular bodies (MVBs) or late endosomes. In several instances, localized regions of the limiting membrane of the MVBs appeared coated, a feature of endosomal membranes not previously described. After RME at the apical PM and passage through the endosomal system, the greater part of both insulin- and LDL-gold conjugates was seen to accumulate in large lysosome-like compartments. However, a small but significant proportion of the internalized ligands was transcytosed and released as discrete membrane-associated quanta at the basal cell surface. The uptake of LDL gold was greatly increased in highly vacuolated, late-passage RVECs. In controls, anti-insulin receptor antibody and excess unconjugated insulin caused up to 89% inhibition in gold-insulin binding and internalization. These results illustrate the internalization and intracellular

  8. The Influence of Receptor-Mediated Interactions on Reaction-Diffusion Mechanisms of Cellular Self-organisation

    Czech Academy of Sciences Publication Activity Database

    Klika, Václav; Baker, R. E.; Headon, D.; Gaffney, E. A.

    2012-01-01

    Roč. 74, č. 4 (2012), s. 935-957 ISSN 0092-8240 Institutional research plan: CEZ:AV0Z20760514 Keywords : reaction-diffusion * receptor-mediated patterning * turing models Subject RIV: BO - Biophysics Impact factor: 2.023, year: 2012 http://www.springerlink.com/content/9713544x6871w4n6/?MUD=MP

  9. Vascular endothelin ET(B) receptor-mediated contraction requires phosphorylation of ERK1/2 proteins

    DEFF Research Database (Denmark)

    Luo, Guogang; Jamali, Roya; Cao, Yong-Xiao

    2006-01-01

    In cardiovascular diseases, endothelin type B (ET(B)) receptors in arterial smooth muscle cells are upregulated. The present study revealed that organ culture of rat mesenteric artery segments enhanced endothelin ET(B) receptor-mediated contraction paralleled with increase in the receptor mRNA an...

  10. Substitution of the Lys linker with the β-Ala linker dramatically decreased the renal uptake of 99mTc-labeled Arg-X-Asp-conjugated and X-Ala-Asp-conjugated α-melanocyte stimulating hormone peptides.

    Science.gov (United States)

    Flook, Adam M; Yang, Jianquan; Miao, Yubin

    2014-11-13

    The purpose of this study was to examine whether the substitution of the Lys linker with the β-Ala could reduce the renal uptake of (99m)Tc-labeled Arg-X-Asp-conjugated and X-Ala-Asp-conjugated α-melanocyte stimulating hormone (α-MSH) peptides. RSD-β-Ala-(Arg(11))CCMSH (1) {c[Arg-Ser-Asp-dTyr-Asp]-β-Ala-Cys-Cys-Glu-His-dPhe-Arg-Trp-Cys-Arg-Pro-Val-NH2}, RTD-β-Ala-(Arg(11))CCMSH (2), RVD-β-Ala-(Arg(11))CCMSH (3), RAD-β-Ala-(Arg(11))CCMSH (4), NAD-β-Ala-(Arg(11))CCMSH (5), and EAD-β-Ala-(Arg(11))CCMSH (6) peptides were synthesized and evaluated for their melanocortin 1 (MC1) receptor binding affinities in B16/F1 melanoma cells. The biodistribution of their (99m)Tc-conjugates were determined in B16/F1 melanoma-bearing C57 mice. The substitution of the Lys linker with β-Ala linker dramatically reduced the renal uptake of all six (99m)Tc-peptides. (99m)Tc-4 exhibited the highest melanoma uptake (15.66 ± 6.19% ID/g) and the lowest kidney uptake (20.18 ± 3.86% ID/g) among these (99m)Tc-peptides at 2 h postinjection. The B16/F1 melanoma lesions could be clearly visualized by single photon emission computed tomography (SPECT)/CT using (99m)Tc-4 as an imaging probe.

  11. Nicotine impairs cyclooxygenase-2-dependent kinin-receptor-mediated murine airway relaxations

    International Nuclear Information System (INIS)

    Xu, Yuan; Cardell, Lars-Olaf

    2014-01-01

    Introduction: Cigarette smoke induces local inflammation and airway hyperreactivity. In asthmatics, it worsens the symptoms and increases the risk for exacerbation. The present study investigates the effects of nicotine on airway relaxations in isolated murine tracheal segments. Methods: Segments were cultured for 24 h in the presence of vehicle, nicotine (10 μM) and/or dexamethasone (1 μM). Airway relaxations were assessed in myographs after pre-contraction with carbachol (1 μM). Kinin receptors, cyclooxygenase (COX) and inflammatory mediator expressions were assessed by real-time PCR and confocal-microscopy-based immunohistochemistry. Results: The organ culture procedure markedly increased bradykinin- (selective B 2 receptor agonist) and des-Arg 9 -bradykinin- (selective B 1 receptor agonist) induced relaxations, and slightly increased relaxation induced by isoprenaline, but not that induced by PGE 2 . The kinin receptor mediated relaxations were epithelium-, COX-2- and EP2-receptor-dependent and accompanied by drastically enhanced mRNA levels of kinin receptors, as well as inflammatory mediators MCP-1 and iNOS. Increase in COX-2 and mPGES-1 was verified both at mRNA and protein levels. Nicotine selectively suppressed the organ-culture-enhanced relaxations induced by des-Arg 9 -bradykinin and bradykinin, at the same time reducing mPGES-1 mRNA and protein expressions. α7-nicotinic acetylcholine receptor inhibitors α-bungarotoxin and MG624 both blocked the nicotine effects on kinin B 2 receptors, but not those on B 1 . Dexamethasone completely abolished kinin-induced relaxations. Conclusion: It is tempting to conclude that a local inflammatory process per se could have a bronchoprotective component by increasing COX-2 mediated airway relaxations and that nicotine could impede this safety mechanism. Dexamethasone further reduced airway inflammation together with relaxations. This might contribute to the steroid resistance seen in some patients with asthma

  12. Nicotine impairs cyclooxygenase-2-dependent kinin-receptor-mediated murine airway relaxations

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Yuan, E-mail: yuan.xu@ki.se; Cardell, Lars-Olaf

    2014-02-15

    Introduction: Cigarette smoke induces local inflammation and airway hyperreactivity. In asthmatics, it worsens the symptoms and increases the risk for exacerbation. The present study investigates the effects of nicotine on airway relaxations in isolated murine tracheal segments. Methods: Segments were cultured for 24 h in the presence of vehicle, nicotine (10 μM) and/or dexamethasone (1 μM). Airway relaxations were assessed in myographs after pre-contraction with carbachol (1 μM). Kinin receptors, cyclooxygenase (COX) and inflammatory mediator expressions were assessed by real-time PCR and confocal-microscopy-based immunohistochemistry. Results: The organ culture procedure markedly increased bradykinin- (selective B{sub 2} receptor agonist) and des-Arg{sup 9}-bradykinin- (selective B{sub 1} receptor agonist) induced relaxations, and slightly increased relaxation induced by isoprenaline, but not that induced by PGE{sub 2}. The kinin receptor mediated relaxations were epithelium-, COX-2- and EP2-receptor-dependent and accompanied by drastically enhanced mRNA levels of kinin receptors, as well as inflammatory mediators MCP-1 and iNOS. Increase in COX-2 and mPGES-1 was verified both at mRNA and protein levels. Nicotine selectively suppressed the organ-culture-enhanced relaxations induced by des-Arg{sup 9}-bradykinin and bradykinin, at the same time reducing mPGES-1 mRNA and protein expressions. α7-nicotinic acetylcholine receptor inhibitors α-bungarotoxin and MG624 both blocked the nicotine effects on kinin B{sub 2} receptors, but not those on B{sub 1}. Dexamethasone completely abolished kinin-induced relaxations. Conclusion: It is tempting to conclude that a local inflammatory process per se could have a bronchoprotective component by increasing COX-2 mediated airway relaxations and that nicotine could impede this safety mechanism. Dexamethasone further reduced airway inflammation together with relaxations. This might contribute to the steroid resistance seen in

  13. Enhanced NMDA receptor-mediated intracellular calcium signaling in magnocellular neurosecretory neurons in heart failure rats.

    Science.gov (United States)

    Stern, Javier E; Potapenko, Evgeniy S

    2013-08-15

    An enhanced glutamate excitatory function within the hypothalamic supraoptic and paraventricluar nuclei is known to contribute to increased neurosecretory and presympathetic neuronal activity, and hence, neurohumoral activation, during heart failure (HF). Still, the precise mechanisms underlying enhanced glutamate-driven neuronal activity in HF remain to be elucidated. Here, we performed simultaneous electrophysiology and fast confocal Ca²⁺ imaging to determine whether altered N-methyl-d-aspartate (NMDA) receptor-mediated changes in intracellular Ca²⁺ levels (NMDA-ΔCa²⁺) occurred in hypothalamic magnocellular neurosecretory cells (MNCs) in HF rats. We found that activation of NMDA receptors resulted in a larger ΔCa²⁺ in MNCs from HF when compared with sham rats. The enhanced NMDA-ΔCa²⁺ was neither dependent on the magnitude of the NMDA-mediated current (voltage clamp) nor on the degree of membrane depolarization or firing activity evoked by NMDA (current clamp). Differently from NMDA receptor activation, firing activity evoked by direct membrane depolarization resulted in similar changes in intracellular Ca²⁺ in sham and HF rats. Taken together, our results support a relatively selective alteration of intracellular Ca²⁺ homeostasis and signaling following activation of NMDA receptors in MNCs during HF. The downstream functional consequences of such altered ΔCa²⁺ signaling during HF are discussed.

  14. Novel isoforms of the TFIID subunit TAF4 modulate nuclear receptor-mediated transcriptional activity

    International Nuclear Information System (INIS)

    Brunkhorst, Adrian; Neuman, Toomas; Hall, Anita; Arenas, Ernest; Bartfai, Tamas; Hermanson, Ola; Metsis, Madis

    2004-01-01

    The transcription factor TFIID consists of TATA-binding protein (TBP) and TBP-associated factors (TAFs). TAFs are essential for modulation of transcriptional activity but the regulation of TAFs is complex and many important aspects remain unclear. In this study, we have identified and characterized five novel truncated forms of the TFIID subunit TAF4 (TAF II 135). Analysis of the mouse gene structure revealed that all truncations were the results of alternative splicing and resulted in the loss of domains or parts of domains implicated in TAF4 functional interactions. Results from transcriptional assays showed that several of the TAF4 isoforms exerted dominant negative effects on TAF4 activity in nuclear receptor-mediated transcriptional activation. In addition, alternative TAF4 isoforms could be detected in specific cell types. Our results indicate an additional level of complexity in TAF4-mediated regulation of transcription and suggest context-specific roles for these new TAF4 isoforms in transcriptional regulation in vivo

  15. Plant cell surface receptor-mediated signaling - a common theme amid diversity.

    Science.gov (United States)

    He, Yunxia; Zhou, Jinggeng; Shan, Libo; Meng, Xiangzong

    2018-01-29

    Sessile plants employ a diverse array of plasma membrane-bound receptors to perceive endogenous and exogenous signals for regulation of plant growth, development and immunity. These cell surface receptors include receptor-like kinases (RLKs) and receptor-like proteins (RLPs) that harbor different extracellular domains for perception of distinct ligands. Several RLK and RLP signaling pathways converge at the somatic embryogenesis receptor kinases (SERKs), which function as shared co-receptors. A repertoire of receptor-like cytoplasmic kinases (RLCKs) associate with the receptor complexes to relay intracellular signaling. Downstream of the receptor complexes, mitogen-activated protein kinase (MAPK) cascades are among the key signaling modules at which the signals converge, and these cascades regulate diverse cellular and physiological responses through phosphorylation of different downstream substrates. In this Review, we summarize the emerging common theme that underlies cell surface receptor-mediated signaling pathways in Arabidopsis thaliana : the dynamic association of RLKs and RLPs with specific co-receptors and RLCKs for signal transduction. We further discuss how signaling specificities are maintained through modules at which signals converge, with a focus on SERK-mediated receptor signaling. © 2018. Published by The Company of Biologists Ltd.

  16. Muscarinic receptor-mediated inositol tetrakisphosphate response in bovine adrenal chromaffin cells

    International Nuclear Information System (INIS)

    Sanborn, B.B.; Schneider, A.S.

    1990-01-01

    Inositol trisphosphate (IP 3 ), a product of the phosphoinositide cycle, mobilizes intracellular Ca 2+ in many cell types. New evidence suggests that inositol tetrakisphosphate (IP 4 ), an IP 3 derivative, may act as another second messenger to further alter calcium homeostasis. However, the function and mechanism of action of IP 4 are presently unresolved. We now report evidence of muscarinic receptor-mediated accumulation of IP 4 in bovine adrenal chromaffin cells, a classic neurosecretory system in which calcium movements have been well studied. Muscarine stimulated an increase in [ 3 H]IP 4 and [ 3 H]IP 3 accumulation in chromaffin cells and this effect was completely blocked by atropine. [ 3 H]IP 4 accumulation was detectable within 15 sec, increased to a maximum by 30 sec and thereafter declined. 2,3-diphosphoglycerate, an inhibitor of IP 3 and IP 4 hydrolysis, enhanced accumulation of these inositol polyphosphates. The results provide the first evidence of a rapid inositol tetrakisphosphate response in adrenal chromaffin cells, which should facilitate the future resolution of the relationship between IP 4 and calcium homeostasis

  17. Electroacupuncture Potentiates Cannabinoid Receptor-Mediated Descending Inhibitory Control in a Mouse Model of Knee Osteoarthritis

    Directory of Open Access Journals (Sweden)

    Xiao-Cui Yuan

    2018-04-01

    Full Text Available Knee osteoarthritis (KOA is a highly prevalent, chronic joint disorder, which can lead to chronic pain. Although electroacupuncture (EA is effective in relieving chronic pain in the clinic, the involved mechanisms remain unclear. Reduced diffuse noxius inhibitory controls (DNIC function is associated with chronic pain and may be related to the action of endocannabinoids. In the present study, we determined whether EA may potentiate cannabinoid receptor-mediated descending inhibitory control and inhibit chronic pain in a mouse model of KOA. We found that the optimized parameters of EA inhibiting chronic pain were the low frequency and high intensity (2 Hz + 1 mA. EA reversed the reduced expression of CB1 receptors and the 2-arachidonoylglycerol (2-AG level in the midbrain in chronic pain. Microinjection of the CB1 receptor antagonist AM251 into the ventrolateral periaqueductal gray (vlPAG can reversed the EA effect on pain hypersensitivity and DNIC function. In addition, CB1 receptors on GABAergic but not glutamatergic neurons are involved in the EA effect on DNIC function and descending inhibitory control of 5-HT in the medulla, thus inhibiting chronic pain. Our data suggest that endocannabinoid (2-AG-CB1R-GABA-5-HT may be a novel signaling pathway involved in the effect of EA improving DNIC function and inhibiting chronic pain.

  18. GABA-A Receptors Mediate Tonic Inhibition and Neurosteroid Sensitivity in the Brain.

    Science.gov (United States)

    Reddy, Doodipala Samba

    2018-01-01

    Neurosteroids like allopregnanolone (AP) are positive allosteric modulators of synaptic and extrasynaptic GABA-A receptors. AP and related neurosteroids exhibit a greater potency for δ-containing extrasynaptic receptors. The δGABA-A receptors, which are expressed extrasynaptically in the dentate gyrus and other regions, contribute to tonic inhibition, promoting network shunting as well as reducing seizure susceptibility. Levels of endogenous neurosteroids fluctuate with ovarian cycle. Natural and synthetic neurosteroids maximally potentiate tonic inhibition in the hippocampus and provide robust protection against a variety of limbic seizures and status epilepticus. Recently, a consensus neurosteroid pharmacophore model has been proposed at extrasynaptic δGABA-A receptors based on structure-activity relationship for functional activation of tonic currents and seizure protection. Aside from anticonvulsant actions, neurosteroids have been found to be powerful anxiolytic and anesthetic agents. Neurosteroids and Zn 2+ have preferential affinity for δ-containing receptors. Thus, Zn 2+ can prevent neurosteroid activation of extrasynaptic δGABA-A receptor-mediated tonic inhibition. Recently, we demonstrated that Zn 2+ selectively inhibits extrasynaptic δGABA-A receptors and thereby fully prevents AP activation of tonic inhibition and seizure protection. We confirmed that neurosteroids exhibit greater sensitivity at extrasynaptic δGABA-A receptors. Overall, extrasynaptic GABA-A receptors are primary mediators of tonic inhibition in the brain and play a key role in the pathophysiology of epilepsy and other neurological disorders. © 2018 Elsevier Inc. All rights reserved.

  19. Beta receptor-mediated modulation of the late positive potential in humans.

    Science.gov (United States)

    de Rover, Mischa; Brown, Stephen B R E; Boot, Nathalie; Hajcak, Greg; van Noorden, Martijn S; van der Wee, Nic J A; Nieuwenhuis, Sander

    2012-02-01

    Electrophysiological studies have identified a scalp potential, the late positive potential (LPP), which is modulated by the emotional intensity of observed stimuli. Previous work has shown that the LPP reflects the modulation of activity in extrastriate visual cortical structures, but little is known about the source of that modulation. The present study investigated whether beta-adrenergic receptors are involved in the generation of the LPP. We used a genetic individual differences approach (experiment 1) and a pharmacological manipulation (experiment 2) to test the hypothesis that the LPP is modulated by the activation of β-adrenergic receptors. In experiment 1, we found that LPP amplitude depends on allelic variation in the β1-receptor gene polymorphism. In experiment 2, we found that LPP amplitude was modulated by the β-blocker propranolol in a direction dependent on subjects' level of trait anxiety: In participants with lower trait anxiety, propranolol led to a (nonsignificant) decrease in the LPP modulation; in participants with higher trait anxiety, propranolol increased the emotion-related LPP modulation. These results provide initial support for the hypothesis that the LPP reflects the downstream effects, in visual cortical areas, of β-receptor-mediated activation of the amygdala.

  20. The effect of vanadate on receptor-mediated endocytosis of asialoorosomucoid in rat liver parenchymal cells

    International Nuclear Information System (INIS)

    Kindberg, G.M.; Gudmundsen, O.; Berg, T.

    1990-01-01

    Vanadate is a phosphate analogue that inhibits enzymes involved in phosphate release and transfer reactions. Since such reactions may play important roles in endocytosis, we studied the effects of vanadate on various steps in receptor-mediated endocytosis of asialoorosomucoid labeled with 125I-tyramine-cellobiose (125I-TC-AOM). The labeled degradation products formed from 125I-TC-AOM are trapped in the lysosomes and may therefore serve as lysosomal markers in subcellular fractionation studies. Vanadate reduced the amount of active surface asialoglycoprotein receptors approximately 70%, but had no effect on the rate of internalization and retroendocytosis of ligand. The amount of surface asialoglycoprotein receptors can be reduced by lowering the incubation temperature gradually from 37 to 15 degrees C; vanadate affected only the temperature--sensitive receptors. Vanadate inhibited degradation of 125I-TC-AOM 70-80%. Degradation was much more sensitive to vanadate than binding; half-maximal effects were seen at approximately 1 mM vanadate for binding and approximately 0.1 mM vanadate for degradation. By subcellular fractionation in sucrose and Nycodenz gradients, it was shown that vanadate completely prevented the transfer of 125I-TC-AOM from endosomes to lysosomes. Therefore, the inhibition of degradation by vanadate was indirect; in the presence of vanadate, ligand did not gain access to the lysosomes. The limited degradation in the presence of vanadate took place in a prelysosomal compartment. Vanadate did not affect cell viability and ATP content

  1. Receptor-mediated inhibition of adenylate cyclase and stimulation of arachidonic acid release in 3T3 fibroblasts. Selective susceptibility to islet-activating protein, pertussis toxin

    International Nuclear Information System (INIS)

    Murayama, T.; Ui, M.

    1985-01-01

    Thrombin exhibited diverse effects on mouse 3T3 fibroblasts. It (a) decreased cAMP in the cell suspension, (b) inhibited adenylate cyclase in the Lubrol-permeabilized cell suspension in a GTP-dependent manner, increased releases of (c) arachidonic acid and (d) inositol from the cell monolayer prelabeled with these labeled compounds, (e) increased 45 Ca 2+ uptake into the cell monolayer, and (f) increased 86 Rb + uptake into the cell monolayer in a ouabain-sensitive manner. Most of the effects were reproduced by bradykinin, platelet-activating factor, and angiotensin II. The receptors for these agonists are thus likely to be linked to three separate effector systems: the adenylate cyclase inhibition, the phosphoinositide breakdown leading to Ca 2+ mobilization and phospholipase A2 activation, and the Na,K-ATPase activation. Among the effects of these agonists, (a), (b), (c), and (e) were abolished, but (d) and (f) were not, by prior treatment of the cells with islet-activating protein (IAP), pertussis toxin, which ADP-ribosylates the Mr = 41,000 protein, the alpha-subunit of the inhibitory guanine nucleotide regulatory protein (Ni), thereby abolishing receptor-mediated inhibition of adenylate cyclase. The effects (a), (c), (d), and (e) of thrombin, but not (b), were mimicked by A23187, a calcium ionophore. The effects of A23187, in contrast to those of receptor agonists, were not affected by the treatment of cells with IAP. Thus, the IAP substrate, the alpha-subunit of Ni, or the protein alike, may play an additional role in signal transduction arising from the Ca 2+ -mobilizing receptors, probably mediating process(es) distal to phosphoinositide breakdown and proximal to Ca 2+ gating

  2. Striatal adenosine A2A receptor-mediated positron emission tomographic imaging in 6-hydroxydopamine-lesioned rats using [18F]-MRS5425

    International Nuclear Information System (INIS)

    Bhattacharjee, Abesh Kumar; Lang Lixin; Jacobson, Orit; Shinkre, Bidhan; Ma Ying; Niu Gang; Trenkle, William C.; Jacobson, Kenneth A.; Chen Xiaoyuan; Kiesewetter, Dale O.

    2011-01-01

    Introduction: A 2A receptors are expressed in the basal ganglia, specifically in striatopallidal GABAergic neurons in the striatum (caudate-putamen). This brain region undergoes degeneration of presynaptic dopamine projections and depletion of dopamine in Parkinson's disease. We developed an 18 F-labeled A 2A analog radiotracer ([ 18 F]-MRS5425) for A 2A receptor imaging using positron emission tomography (PET). We hypothesized that this tracer could image A 2A receptor changes in the rat model for Parkinson's disease, which is created following unilateral injection of the monoaminergic toxin 6-hydroxydopamine (6-OHDA) into the substantia nigra. Methods: [ 18 F]-MRS5425 was injected intravenously in anesthetized rats, and PET imaging data were collected. Image-derived percentage injected doses per gram (%ID/g) in regions of interest was measured in the striatum of normal rats and in rats unilaterally lesioned with 6-OHDA after intravenous administration of saline (baseline), D 2 agonist quinpirole (1.0 mg/kg) or D 2 antagonist raclopride (6.0 mg/kg). Results: Baseline %ID/g reached a maximum at 90 s and maintained plateau for 3.5 min, and then declined slowly thereafter. In 6-OHDA-lesioned rats, %ID/g was significantly higher in the lesioned side compared to the intact side, and the baseline total %ID/g (data from both hemispheres were combined) was significantly higher compared to quinpirole stimulation starting from 4.5 min until the end of acquisition at 30 min. Raclopride did not produce any change in uptake compared to baseline or between the hemispheres. Conclusion: Thus, increase of A 2A receptor-mediated uptake of radioactive MRS5425 could be a superior molecular target for Parkinson's imaging.

  3. Striatal adenosine A{sub 2A} receptor-mediated positron emission tomographic imaging in 6-hydroxydopamine-lesioned rats using [{sup 18}F]-MRS5425

    Energy Technology Data Exchange (ETDEWEB)

    Bhattacharjee, Abesh Kumar; Lang Lixin; Jacobson, Orit [Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892 (United States); Shinkre, Bidhan [Chemical Biology Unit, Laboratory of Cell Biochemistry and Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 (United States); Ma Ying [Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892 (United States); Niu Gang [Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892 (United States); Department of Radiology and Imaging Sciences, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892 (United States); Trenkle, William C. [Chemical Biology Unit, Laboratory of Cell Biochemistry and Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 (United States); Jacobson, Kenneth A. [Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 (United States); Chen Xiaoyuan [Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892 (United States); Kiesewetter, Dale O., E-mail: dk7k@nih.gov [Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892 (United States)

    2011-08-15

    Introduction: A{sub 2A} receptors are expressed in the basal ganglia, specifically in striatopallidal GABAergic neurons in the striatum (caudate-putamen). This brain region undergoes degeneration of presynaptic dopamine projections and depletion of dopamine in Parkinson's disease. We developed an {sup 18}F-labeled A{sub 2A} analog radiotracer ([{sup 18}F]-MRS5425) for A{sub 2A} receptor imaging using positron emission tomography (PET). We hypothesized that this tracer could image A{sub 2A} receptor changes in the rat model for Parkinson's disease, which is created following unilateral injection of the monoaminergic toxin 6-hydroxydopamine (6-OHDA) into the substantia nigra. Methods: [{sup 18}F]-MRS5425 was injected intravenously in anesthetized rats, and PET imaging data were collected. Image-derived percentage injected doses per gram (%ID/g) in regions of interest was measured in the striatum of normal rats and in rats unilaterally lesioned with 6-OHDA after intravenous administration of saline (baseline), D{sub 2} agonist quinpirole (1.0 mg/kg) or D{sub 2} antagonist raclopride (6.0 mg/kg). Results: Baseline %ID/g reached a maximum at 90 s and maintained plateau for 3.5 min, and then declined slowly thereafter. In 6-OHDA-lesioned rats, %ID/g was significantly higher in the lesioned side compared to the intact side, and the baseline total %ID/g (data from both hemispheres were combined) was significantly higher compared to quinpirole stimulation starting from 4.5 min until the end of acquisition at 30 min. Raclopride did not produce any change in uptake compared to baseline or between the hemispheres. Conclusion: Thus, increase of A{sub 2A} receptor-mediated uptake of radioactive MRS5425 could be a superior molecular target for Parkinson's imaging.

  4. Positron emission tomography of tumour [{sup 18}F]fluoroestradiol uptake in patients with acquired hormone-resistant metastatic breast cancer prior to oestradiol therapy

    Energy Technology Data Exchange (ETDEWEB)

    Kruchten, Michel van; Schroeder, Carolien P.; Vries, Elisabeth G.E. de; Hospers, Geke A.P. [University of Groningen, Department of Medical Oncology, University Medical Centre Groningen (Netherlands); Glaudemans, Andor W.J.M.; Vries, Erik F.J. de [University of Groningen, Department of Nuclear Medicine and Molecular Imaging, University Medical Centre Groningen (Netherlands)

    2015-10-15

    Whereas anti-oestrogen therapy is widely applied to treat oestrogen receptor (ER) positive breast cancer, paradoxically, oestrogens can also induce tumour regression. Up-regulation of ER expression is a marker for oestrogen hypersensitivity. We, therefore, performed an exploratory study to evaluate positron emission tomography (PET) with the tracer 16α-[{sup 18}F]fluoro-17β-oestradiol ({sup 18}F-FES) as potential marker to select breast cancer patients for oestradiol therapy. Eligible patients had acquired endocrine-resistant metastatic breast cancer that progressed after ≥2 lines of endocrine therapy. All patients had prior ER-positive histology. Treatment consisted of oestradiol 2 mg, three times daily, orally. Patients underwent {sup 18}F-FES-PET/CT imaging at baseline. Tumour {sup 18}F-FES-uptake was quantified for a maximum of 20 lesions and expressed as maximum standardised uptake value (SUV{sub max}). CT-scan was repeated every 3 months to evaluate treatment response. Clinical benefit was defined as time to radiologic or clinical progression ≥24 weeks. {sup 18}F-FES uptake, quantified for 255 lesions in 19 patients, varied greatly between lesions (median 2.8; range 0.6-24.3) and between patients (median 2.5; range 1.1-15.5). Seven (37 %) patients experienced clinical benefit of oestrogen therapy, eight progressed (PD), and four were non-evaluable due to side effects. The positive and negative predictive value (PPV/NPV) of {sup 18}F-FES-PET for response to treatment were 60 % (95 % CI: 31-83 %) and 80 % (95 % CI: 38-96 %), respectively, using SUV{sub max} >1.5. {sup 18}F-FES-PET may aid identification of patients with acquired antihormone resistant breast cancer that are unlikely to benefit from oestradiol therapy. (orig.)

  5. Stimulation by parathyroid hormone of sup 45 Ca sup 2+ uptake in osteoblast-like cells: Possible involvement of alkaline phosphatase

    Energy Technology Data Exchange (ETDEWEB)

    Fukayama, S.; Tashjian, A.H. Jr. (Harvard School of Public Health, Boston, MA (USA))

    1990-04-01

    We have investigated the actions of human PTH (hPTH-(1-34)) on the association of 45Ca2+ with two human (SaOS-2 and MG-63) and two rat (ROS 17/2.8 and UMR-106) osteoblast-like cell types. In SaOS-2 cells, hPTH-(1-34) binds to specific membrane receptors to activate adenylate cyclase. Treatment of SaOS-2 cells with hPTH-(1-34) resulted in an increase in 45Ca2+ uptake, in a dose-dependent fashion, up to 2- to 4-fold above control values. The increase was first evident at 10 min and persisted for at least 30 min. Treatment with nimodipine, a calcium channel antagonist, was without effect on the stimulatory action of PTH. A similar enhancement of cell-associated 45Ca2+ was observed when the cells were incubated with vasoactive intestinal peptide, which acts via different receptors to activate adenylate cyclase in SaOS-2 cells. Treatment with (Bu)2cAMP also induced an increase in cell-associated 45Ca2+. Pretreatment of SaOS-2 cells with hPTH-(1-34) for 4 h, which induced homologous desensitization to a second challenge with the same peptide for stimulation of cAMP production, did not attenuate the further enhancement of cell-associated 45Ca2+ by a second treatment with hPTH-(1-34). We then examined a possible relationship between alkaline phosphatase (ALPase) and 45Ca2+ uptake. SaOS-2 cells contained high levels of alkaline phosphatase activity and continuously released the enzyme into the medium. Release was enhanced by treatment with hPTH-(1-34) for 10 min. Incubation of cells with levamisole (an inhibitor of the liver/bone/kidney type of ALPase) resulted in a rapid decrease in basal and PTH-stimulated 45Ca2+ uptake, while treatment with L-Phe-Gly-Gly was without effect. Treatment of the cells with ALPase (bovine kidney) enhanced 45Ca2+ uptake. In MG-63 cells, a stimulatory effect of hPTH-(1-34) on cell-associated 45Ca2+ was also observed; however, hPTH-(1-34) did not stimulate cAMP production in MG-63 cells.

  6. A pp32-retinoblastoma protein complex modulates androgen receptor-mediated transcription and associates with components of the splicing machinery

    International Nuclear Information System (INIS)

    Adegbola, Onikepe; Pasternack, Gary R.

    2005-01-01

    We have previously shown pp32 and the retinoblastoma protein interact. pp32 and the retinoblastoma protein are nuclear receptor transcriptional coregulators: the retinoblastoma protein is a coactivator for androgen receptor, the major regulator of prostate cancer growth, while pp32, which is highly expressed in prostate cancer, is a corepressor of the estrogen receptor. We now show pp32 increases androgen receptor-mediated transcription and the retinoblastoma protein modulates this activity. Using affinity purification and mass spectrometry, we identify members of the pp32-retinoblastoma protein complex as PSF and nonO/p54nrb, proteins implicated in coordinate regulation of nuclear receptor-mediated transcription and splicing. We show that the pp32-retinoblastoma protein complex is modulated during TPA-induced K562 differentiation. Present evidence suggests that nuclear receptors assemble multiprotein complexes to coordinately regulate transcription and mRNA processing. Our results suggest that pp32 and the retinoblastoma protein may be part of a multiprotein complex that coordinately regulates nuclear receptor-mediated transcription and mRNA processing

  7. Influence of ER leak on resting cytoplasmic Ca2+ and receptor-mediated Ca2+ signalling in human macrophage.

    Science.gov (United States)

    Layhadi, Janice A; Fountain, Samuel J

    2017-06-03

    Mechanisms controlling endoplasmic reticulum (ER) Ca 2+ homeostasis are important regulators of resting cytoplasmic Ca 2+ concentration ([Ca 2+ ] cyto ) and receptor-mediated Ca 2+ signalling. Here we investigate channels responsible for ER Ca 2+ leak in THP-1 macrophage and human primary macrophage. In the absence of extracellular Ca 2+ we employ ionomycin action at the plasma membrane to stimulate ER Ca 2+ leak. Under these conditions ionomycin elevates [Ca 2+ ] cyto revealing a Ca 2+ leak response which is abolished by thapsigargin. IP 3 receptors (Xestospongin C, 2-APB), ryanodine receptors (dantrolene), and translocon (anisomycin) inhibition facilitated ER Ca 2+ leak in model macrophage, with translocon inhibition also reducing resting [Ca 2+ ] cyto . In primary macrophage, translocon inhibition blocks Ca 2+ leak but does not influence resting [Ca 2+ ] cyto . We identify a role for translocon-mediated ER Ca 2+ leak in receptor-mediated Ca 2+ signalling in both model and primary human macrophage, whereby the Ca 2+ response to ADP (P2Y receptor agonist) is augmented following anisomycin treatment. In conclusion, we demonstrate a role of ER Ca 2+ leak via the translocon in controlling resting cytoplasmic Ca 2+ in model macrophage and receptor-mediated Ca 2+ signalling in model macrophage and primary macrophage. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Intrinsically disordered cytoplasmic domains of two cytokine receptors mediate conserved interactions with membranes

    DEFF Research Database (Denmark)

    Haxholm, Gitte Wolfsberg; Nikolajsen, Louise Fletcher; Olsen, Johan Gotthardt

    2015-01-01

    . This study presents the first comprehensive structural characterization of any cytokine receptor ICD and demonstrates that the human prolactin and growth hormone receptor ICDs are intrinsically disordered throughout their entire lengths. We show that they interact specifically with hallmark lipids...

  9. The Role of Estrogen Related Receptor in Modulating Estrogen Receptor Mediated Transcription in Breast Cancer Cells

    Science.gov (United States)

    2005-04-01

    tumors correlates with an unfavorable prognosis (Ariazi 2002; Lu 2001; Suzuki 2004; Vanacker 1999). The transcriptional activity of ERRa is not inhibited...SA. 101:6570-5. Needham, M ., S. Raines, J. McPheat, C. Stacey, J. Ellston, S. Hoare, and M . Parker. 2000. Differential interaction of steroid hormone...R. Graves, M . Wright, and B.M. Spiegelman. 1998. A cold- inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell. 92:829- 39

  10. Decreased α1-adrenergic receptor-mediated inositide hydrolysis in neurons from hypertensive rat brain

    International Nuclear Information System (INIS)

    Feldstein, J.B.; Gonzales, R.A.; Baker, S.P.; Sumners, C.; Crews, F.T.; Raizada, M.K.

    1986-01-01

    The expression of α 1 -adrenergic receptors and norepinephrine (NE)-stimulated hydrolysis of inositol phospholipid has been studied in neuronal cultures from the brains of normotensive (Wistar-Kyoto, WKY) and spontaneously hypertensive (SH) rats. Binding of 125 I-1-[β-(4-hydroxyphenyl)-ethyl-aminomethyl] tetralone (HEAT) to neuronal membranes was 68-85% specific and was rapid. Competition-inhibition experiments with various agonists and antagonists suggested that 125 I-HEAT bound selectively to α 1 -adrenergic receptors. Specific binding of 125 I-HEAT to neuronal membranes from SH rat brain cultures was 30-45% higher compared with binding in WKY normotensive controls. This increase was attributed to an increase in the number of α 1 -adrenergic receptors on SH rat brain neurons. Incubation of neuronal cultures of rat brain from both strains with NE resulted in a concentration-dependent stimulation of release of inositol phosphates, although neurons from SH rat brains were 40% less responsive compared with WKY controls. The decrease in responsiveness of SH rat brain neurons to NE, even though the α 1 -adrenergic receptors are increased, does not appear to be due to a general defect in membrane receptors and postreceptor signal transduction mechanisms. This is because neither the number of muscarinic-cholinergic receptors nor the carbachol-stimulated release of inositol phosphates is different in neuronal cultures from the brains of SH rats compared with neuronal cultures from the brains of WKY rats. These observations suggest that the increased expression of α 1 -adrenergic receptors does not parallel the receptor-mediated inositol phosphate hydrolysis in neuronal cultures from SH rat brain

  11. Milrinone attenuates thromboxane receptor-mediated hyperresponsiveness in hypoxic pulmonary arterial myocytes.

    Science.gov (United States)

    Santhosh, K T; Elkhateeb, O; Nolette, N; Outbih, O; Halayko, A J; Dakshinamurti, S

    2011-07-01

    Neonatal pulmonary hypertension (PPHN) is characterized by pulmonary vasoconstriction, due in part to dysregulation of the thromboxane prostanoid (TP) receptor. Hypoxia induces TP receptor-mediated hyperresponsiveness, whereas serine phosphorylation mediates desensitization of TP receptors. We hypothesized that prostacyclin (IP) receptor activity induces TP receptor phosphorylation and decreases ligand affinity; that TP receptor sensitization in hypoxic myocytes is due to IP receptor inactivation; and that this would be reversible by the cAMP-specific phosphodiesterase inhibitor milrinone. We examined functional regulation of TP receptors by serine phosphorylation and effects of IP receptor stimulation and protein kinase A (PKA) activity on TP receptor sensitivity in myocytes from neonatal porcine resistance pulmonary arteries after 72 h hypoxia in vitro. Ca(2+) response curves to U46619 (TP receptor agonist) were determined in hypoxic and normoxic myocytes incubated with or without iloprost (IP receptor agonist), forskolin (adenylyl cyclase activator), H8 (PKA inhibitor) or milrinone. TP and IP receptor saturation binding kinetics were measured in presence of iloprost or 8-bromo-cAMP. Ligand affinity for TP receptors was normalized in vitro by IP receptor signalling intermediates. However, IP receptor affinity was compromised in hypoxic myocytes, decreasing cAMP production. Milrinone normalized TP receptor sensitivity in hypoxic myocytes by restoring PKA-mediated regulatory TP receptor phosphorylation. TP receptor sensitivity and EC(50) for TP receptor agonists was regulated by PKA, as TP receptor serine phosphorylation by PKA down-regulated Ca(2+) mobilization. Hypoxia decreased IP receptor activity and cAMP generation, inducing TP receptor hyperresponsiveness, which was reversed by milrinone. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

  12. PKCɛ mediates substance P inhibition of GABAA receptors-mediated current in rat dorsal root ganglion.

    Science.gov (United States)

    Li, Li; Zhao, Lei; Wang, Yang; Ma, Ke-tao; Shi, Wen-yan; Wang, Ying-zi; Si, Jun-qiang

    2015-02-01

    The mechanism underlying the modulatory effect of substance P (SP) on GABA-activated response in rat dorsal root ganglion (DRG) neurons was investigated. In freshly dissociated rat DRG neurons, whole-cell patch-clamp technique was used to record GABA-activated current and sharp electrode intracellular recording technique was used to record GABA-induced membrane depolarization. Application of GABA (1-1000 μmol/L) induced an inward current in a concentration-dependent manner in 114 out of 127 DRG neurons (89.8 %) examined with whole-cell patch-clamp recordings. Bath application of GABA (1-1000 μmol/L) evoked a depolarizing response in 236 out of 257 (91.8%) DRG neurons examined with intracellular recordings. Application of SP (0.001-1 μmol/L) suppressed the GABA-activated inward current and membrane depolarization. The inhibitory effects were concentration-dependent and could be blocked by the selective neurokinin 1 (NK1) receptors antagonist spantide but not by L659187 and SR142801 (1 μmol/L, n=7), selective antagonists of NK2 and NK3. The inhibitory effect of SP was significantly reduced by the calcium chelator BAPTA-AM, phospholipase C (PLC) inhibitor U73122, and PKC inhibitor chelerythrine, respectively. The PKA inhibitor H-89 did not affect the SP effect. Remarkably, the inhibitory effect of SP on GABA-activated current was nearly completely removed by a selective PKCε inhibitor epilon-V1-2 but not by safingol and LY333531, selective inhibitors of PKCα and PKCβ. Our results suggest that NK1 receptor mediates SP-induced inhibition of GABA-activated current and membrane depolarization by activating intracellular PLC-Ca²⁺-PKCε cascade. SP might regulate the excitability of peripheral nociceptors through inhibition of the "pre-synaptic inhibition" evoked by GABA, which may explain its role in pain and neurogenic inflammation.

  13. Receptor-mediated endocytosis generates nanomechanical force reflective of ligand identity and cellular property.

    Science.gov (United States)

    Zhang, Xiao; Ren, Juan; Wang, Jingren; Li, Shixie; Zou, Qingze; Gao, Nan

    2018-08-01

    Whether environmental (thermal, chemical, and nutrient) signals generate quantifiable, nanoscale, mechanophysical changes in the cellular plasma membrane has not been well elucidated. Assessment of such mechanophysical properties of plasma membrane may shed lights on fundamental cellular process. Atomic force microscopic (AFM) measurement of the mechanical properties of live cells was hampered by the difficulty in accounting for the effects of the cantilever motion and the associated hydrodynamic force on the mechanical measurement. These challenges have been addressed in our recently developed control-based AFM nanomechanical measurement protocol, which enables a fast, noninvasive, broadband measurement of the real-time changes in plasma membrane elasticity in live cells. Here we show using this newly developed AFM platform that the plasma membrane of live mammalian cells exhibits a constant and quantifiable nanomechanical property, the membrane elasticity. This mechanical property sensitively changes in response to environmental factors, such as the thermal, chemical, and growth factor stimuli. We demonstrate that different chemical inhibitors of endocytosis elicit distinct changes in plasma membrane elastic modulus reflecting their specific molecular actions on the lipid configuration or the endocytic machinery. Interestingly, two different growth factors, EGF and Wnt3a, elicited distinct elastic force profiles revealed by AFM at the plasma membrane during receptor-mediated endocytosis. By applying this platform to genetically modified cells, we uncovered a previously unknown contribution of Cdc42, a key component of the cellular trafficking network, to EGF-stimulated endocytosis at plasma membrane. Together, this nanomechanical AFM study establishes an important foundation that is expandable and adaptable for investigation of cellular membrane evolution in response to various key extracellular signals. © 2017 Wiley Periodicals, Inc.

  14. Decrement of GABAA receptor-mediated inhibitory postsynaptic currents in dentate granule cells in epileptic hippocampus.

    Science.gov (United States)

    Isokawa, M

    1996-05-01

    1. Inhibitory postsynaptic currents (IPSCs) were studied in hippocampal dentate granule cells (DGCs) in the pilocarpine model and human temporal lobe epilepsy, with the use of the whole cell patch-clamp recording technique in slice preparations. 2. In the pilocarpine model, hippocampal slices were prepared from rats that were allowed to experience spontaneous seizures for 2 mo. Human hippocampal specimens were obtained from epileptic patients who underwent surgical treatment for medically intractable seizures. 3. IPSCs were generated by single perforant path stimulation and recorded at a membrane potential (Vm) of 0 mV near the reversal potential of glutamate excitatory postsynaptic currents in the voltage-clamp recording. IPSCs were pharmacologically identified as gamma-aminobutyric acid-A (GABAA) IPSCs by 10 microM bicuculline methiodide. 4. During low-frequency stimulation, IPSCs were not different in amplitude among non-seizure-experienced rat hippocampi, human nonsclerotic hippocampi, seizure-experienced rat hippocampi, and human sclerotic hippocampi. In the last two groups of DGCs, current-clamp recordings indicated the presence of prolonged excitatory postsynaptic potentials (EPSPs) mediated by the N-methyl-D-aspartate (NMDA) receptor. 5. High-frequency stimulation, administered at Vm = -30 mV to activate NMDA currents, reduced GABAA IPSC amplitude specifically in seizure-experienced rat hippocampi (t = 2.5, P < 0.03) and human sclerotic hippocampi (t = 7.7, P < 0.01). This reduction was blocked by an NMDA receptor antagonist, 2-amino-5-phosphonovaleric acid (APV) (50 microM). The time for GABAA IPSCs to recover to their original amplitude was also shortened by the application of APV. 6. I conclude that, when intensively activated, NMDA receptor-mediated excitatory transmission may interact with GABAergic synaptic inhibition in DGCs in seizure-experienced hippocampus to transiently reduce GABA(A) receptor-channel function. Such interactions may contribute to

  15. Receptor-mediated transcytosis of cyclophilin B through the blood-brain barrier.

    Science.gov (United States)

    Carpentier, M; Descamps, L; Allain, F; Denys, A; Durieux, S; Fenart, L; Kieda, C; Cecchelli, R; Spik, G

    1999-07-01

    Cyclophilin B (CyPB) is a cyclosporin A (CsA)-binding protein mainly located in intracellular vesicles and secreted in biological fluids. In previous works, we demonstrated that CyPB interacts with T lymphocytes and enhances in vitro cellular incorporation and activity of CsA. In addition to its immunosuppressive activity, CsA is able to promote regeneration of damaged peripheral nerves. However, the crossing of the drug from plasma to neural tissue is restricted by the relative impermeability of the blood-brain barrier. To know whether CyPB might also participate in the delivery of CsA into the brain, we have analyzed the interactions of CyPB with brain capillary endothelial cells. First, we demonstrated that CyPB binds to two types of binding sites present at the surface of capillary endothelial cells from various species of tissues. The first type of binding sites (K(D) = 300 nM; number of sites = 3 x 10(6)) is related to interactions with negatively charged compounds such as proteoglycans. The second type of binding sites, approximately 50,000 per cell, exhibits a higher affinity for CyPB (K(D) = 15 nM) and is involved in an endocytosis process, indicating it might correspond to a functional receptor. Finally, the use of an in vitro model of blood-brain barrier allowed us to demonstrate that CyPB is transcytosed by a receptor-mediated pathway (flux = 16.5 fmol/cm2/h). In these conditions, CyPB did not significantly modify the passage of CsA, indicating that it is unlikely to provide a pathway for CsA brain delivery.

  16. NMDA receptors mediate neuron-to-glia signaling in mouse cortical astrocytes.

    Science.gov (United States)

    Lalo, Ulyana; Pankratov, Yuri; Kirchhoff, Frank; North, R Alan; Verkhratsky, Alexei

    2006-03-08

    Chemical transmission between neurons and glial cells is an important element of integration in the CNS. Here, we describe currents activated by NMDA in cortical astrocytes, identified in transgenic mice that express enhanced green fluorescent protein under control of the human glial fibrillary acidic protein promoter. Astrocytes were studied by whole-cell voltage clamp either in slices or after gentle nonenzymatic mechanical dissociation. Acutely isolated astrocytes showed a three-component response to glutamate. The initial rapid component was blocked by 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide (NBQX), which is an antagonist of AMPA receptors (IC50, 2 microM), and the NMDA receptor antagonist D-AP-5 blocked the later sustained component (IC50, 0.6 microM). The third component of glutamate application response was sensitive to D,L-threo-beta-benzyloxyaspartate, a glutamate transporter blocker. Fast application of NMDA evoked concentration-dependent inward currents (EC50, 0.3 microM); these showed use-dependent block by (+)-5-methyl-10,11-dihydro-5H-dibenzo [a,d] cyclohepten-5,10-imine maleate (MK-801). These NMDA-evoked currents were linearly dependent on membrane potential and were not affected by extracellular magnesium at concentrations up to 10 mM. Electrical stimulation of axons in layer IV-VI induced a complex inward current in astrocytes situated in the cortical layer II, part of which was sensitive to MK-801 at holding potential -80 mV and was not affected by the AMPA glutamate receptor antagonist NBQX. The fast miniature spontaneous currents were observed in cortical astrocytes in slices as well. These currents exhibited both AMPA and NMDA receptor-mediated components. We conclude that cortical astrocytes express functional NMDA receptors that are devoid of Mg2+ block, and these receptors are involved in neuronal-glial signal transmission.

  17. P2X receptor-mediated ATP purinergic signaling in health and disease

    Directory of Open Access Journals (Sweden)

    Jiang LH

    2012-09-01

    Full Text Available Lin-Hua JiangSchool of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds, United KingdomAbstract: Purinergic P2X receptors are plasma membrane proteins present in a wide range of mammalian cells where they act as a cellular sensor, enabling cells to detect and respond to extracellular adenosine triphosphate (ATP, an important signaling molecule. P2X receptors function as ligand-gated Ca2+-permeable cationic channels that open upon ATP binding to elevate intracellular Ca2+ concentrations and cause membrane depolarization. In response to sustained activation, P2X receptors induce formation of a pore permeable to large molecules. P2X receptors also interact with distinct functional proteins and membrane lipids to form specialized signaling complexes. Studies have provided compelling evidence to show that such P2X receptor-mediated ATP-signaling mechanisms determine and regulate a growing number and diversity of important physiological processes, including neurotransmission, muscle contraction, and cytokine release. There is accumulating evidence to support strong causative relationships of altered receptor expression and function with chronic pain, inflammatory diseases, cancers, and other pathologies or diseases. Numerous high throughput screening drug discovery programs and preclinical studies have thus far demonstrated the proof of concepts that the P2X receptors are druggable targets and selective receptor antagonism is a promising therapeutics approach. This review will discuss the recent progress in understanding the mammalian P2X receptors with respect to the ATP-signaling mechanisms, physiological and pathophysiological roles, and development and preclinical studies of receptor antagonists.Keywords: extracellular ATP, ion channel, large pore, signaling complex, chronic pain, inflammatory diseases

  18. Receptor-mediated endocytosis of low density lipoproteins in aortic endothelial cells

    International Nuclear Information System (INIS)

    Sanan, D.A.

    1986-04-01

    Lipoprotein binding and metabolism in actively-dividing (subconfluent) and quiescent (postconfluent) bovine aortic endothelial cells (ECs) were qualitatively investigated by fluorescence microscopy using dioctadecylindocarbocyanine-labelled lipoproteins and by indirect immunofluorescence microscopy. LDL and acetylated-LDL (AcLDL) were seen bound to the surfaces of subconfluent ECs (at 4 degrees C or at 37 degrees C), as a random distribution of punctate foci. ECs therefore closely resembled fibroblasts in the distribution of LDL receptors on their surfaces. No binding of LDL was seen on postconfluent EC surfaces by either direct or indirect fluorescence microscopy. The patterns of AcLDL binding on postconfluent ECs resembled those on subconfluent ECs. Intracellular LDL and AcLDL occurred as perinuclear accumulations of large fluorescent disc-shaped profiles in subconfluent ECs. These accumulations were shown to arise from surface-bound material by pulse-chase experiments. Intracellular LDL was absent in the majority of postconfluent ECs, while AcLDL accumulation was massive. 'Wounding' of cultures allowed simultaneous assessment of lipoprotein metabolism in quiescent and actively-dividing areas of the same culture. It is concluded that postconfluent quiescent bovine aortic ECs in vitro metabolise virtually no LDL via the LDL-receptor pathway due to a vanishingly low number of LDL receptors. This contrasts with the ability of postconfluent cells to metabolise relatively large amounts of AcLDL via a receptor-mediated mechanism. The significance of these conclusions is discussed with respect to the interaction of plasma lipoproteins with the endothelium in vivo. 301 refs

  19. Do mollusks use vertebrate sex steroids as reproductive hormones? Part I: Critical appraisal of the evidence for the presence, biosynthesis and uptake of steroids.

    Science.gov (United States)

    Scott, Alexander P

    2012-11-01

    The consensus view is that vertebrate-type steroids are present in mollusks and perform hormonal roles which are similar to those that they play in vertebrates. Although vertebrate steroids can be measured in molluscan tissues, a key question is 'Are they formed endogenously or they are picked up from their environment?'. The present review concludes that there is no convincing evidence for biosynthesis of vertebrate steroids by mollusks. Furthermore, the 'mollusk' genome does not contain the genes for key enzymes that are necessary to transform cholesterol in progressive steps into vertebrate-type steroids; nor does the mollusk genome contain genes for functioning classical nuclear steroid receptors. On the other hand, there is very strong evidence that mollusks are able to absorb vertebrate steroids from the environment; and are able to store some of them (by conjugating them to fatty acids) for weeks to months. It is notable that the three steroids that have been proposed as functional hormones in mollusks (i.e. progesterone, testosterone and 17β-estradiol) are the same as those of humans. Since humans (and indeed all vertebrates) continuously excrete steroids not just via urine and feces, but via their body surface (and, in fish, via the gills), it is impossible to rule out contamination as the sole reason for the presence of vertebrate steroids in mollusks (even in animals kept under supposedly 'clean laboratory conditions'). Essentially, the presence of vertebrate steroids in mollusks cannot be taken as reliable evidence of either endogenous biosynthesis or of an endocrine role. Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.

  20. The maximum standardized uptake value of 18 F-FDG PET scan to determine prognosis of hormone-receptor positive metastatic breast cancer

    Directory of Open Access Journals (Sweden)

    Zhang Jian

    2013-01-01

    Full Text Available Abstract Background Whether PET scan maximum standard uptake value (SUVmax could differentiate luminal A from luminal B and help predict the survival of metastatic breast cancer (MBC patients with luminal subtype is still unknown and need to be investigated. Methods 305 MBC patients with luminal subtypes were screened with PET/CT. Eligible patients were prospectively followed up. Results In total, 134 patients were eligible for this study. SUVmax was significantly related to the number of metastatic sites and presence of visceral metastasis on univariate analysis. SUVmax could not effectively differentiate patients with luminal A from luminal B subtype. Although luminal subtype at diagnosis could predict the relapse-free interval, it could not predict progression-free survival (PFS or overall survival (OS after developing relapse. In contrast, SUVmax was predictive of both PFS and OS and this effect was maintained in multivariate COX regression model. Conclusions SUVmax of MBC did not correlate with molecular subtypes of primary tumor. While molecular subtype may be a valuable prognostic factor at primary diagnosis of breast cancer, the SUVmax, rather than molecular subtype, does have a potential to predict independently in multivariate analysis for the PFS and OS in patients with metastatic disease of luminal subtype.

  1. The maximum standardized uptake value of 18 F-FDG PET scan to determine prognosis of hormone-receptor positive metastatic breast cancer

    International Nuclear Information System (INIS)

    Zhang, Jian; Hu, Xi-Chun; Jia, Zhen; Ragaz, Joseph; Zhang, Ying-Jian; Zhou, Min; Zhang, Yong-Ping; Li, Gang; Wang, Bi-Yun; Wang, Zhong-Hua

    2013-01-01

    Whether PET scan maximum standard uptake value (SUVmax) could differentiate luminal A from luminal B and help predict the survival of metastatic breast cancer (MBC) patients with luminal subtype is still unknown and need to be investigated. 305 MBC patients with luminal subtypes were screened with PET/CT. Eligible patients were prospectively followed up. In total, 134 patients were eligible for this study. SUVmax was significantly related to the number of metastatic sites and presence of visceral metastasis on univariate analysis. SUVmax could not effectively differentiate patients with luminal A from luminal B subtype. Although luminal subtype at diagnosis could predict the relapse-free interval, it could not predict progression-free survival (PFS) or overall survival (OS) after developing relapse. In contrast, SUVmax was predictive of both PFS and OS and this effect was maintained in multivariate COX regression model. SUVmax of MBC did not correlate with molecular subtypes of primary tumor. While molecular subtype may be a valuable prognostic factor at primary diagnosis of breast cancer, the SUVmax, rather than molecular subtype, does have a potential to predict independently in multivariate analysis for the PFS and OS in patients with metastatic disease of luminal subtype

  2. Characterization of murine melanocortin receptors mediating adipocyte lipolysis and examination of signalling pathways involved

    DEFF Research Database (Denmark)

    Møller, Cathrine Laustrup; Raun, Kirsten; Jacobsen, Marianne Lambert

    2011-01-01

    hormone (a-MSH) generated from proopiomelanocortin (POMC), as well as synthetic MSH analogues to stimulate lipolysis in murine 3T3-L1 adipocytes it is shown that MC2R and MC5R are lipolytic mediators in differentiated 3T3-L1 adipocytes. Involvement of cAMP, phosphorylated extracellular signal...

  3. Astrocytes protect neurons against methylmercury via ATP/P2Y(1) receptor-mediated pathways in astrocytes.

    Science.gov (United States)

    Noguchi, Yusuke; Shinozaki, Youichi; Fujishita, Kayoko; Shibata, Keisuke; Imura, Yoshio; Morizawa, Yosuke; Gachet, Christian; Koizumi, Schuichi

    2013-01-01

    Methylmercury (MeHg) is a well known environmental pollutant that induces serious neuronal damage. Although MeHg readily crosses the blood-brain barrier, and should affect both neurons and glial cells, how it affects glia or neuron-to-glia interactions has received only limited attention. Here, we report that MeHg triggers ATP/P2Y1 receptor signals in astrocytes, thereby protecting neurons against MeHg via interleukin-6 (IL-6)-mediated pathways. MeHg increased several mRNAs in astrocytes, among which IL-6 was the highest. For this, ATP/P2Y1 receptor-mediated mechanisms were required because the IL-6 production was (i) inhibited by a P2Y1 receptor antagonist, MRS2179, (ii) abolished in astrocytes obtained from P2Y1 receptor-knockout mice, and (iii) mimicked by exogenously applied ATP. In addition, (iv) MeHg released ATP by exocytosis from astrocytes. As for the intracellular mechanisms responsible for IL-6 production, p38 MAP kinase was involved. MeHg-treated astrocyte-conditioned medium (ACM) showed neuro-protective effects against MeHg, which was blocked by anti-IL-6 antibody and was mimicked by the application of recombinant IL-6. As for the mechanism of neuro-protection by IL-6, an adenosine A1 receptor-mediated pathway in neurons seems to be involved. Taken together, when astrocytes sense MeHg, they release ATP that autostimulates P2Y1 receptors to upregulate IL-6, thereby leading to A1 receptor-mediated neuro-protection against MeHg.

  4. Activation of Brain Somatostatin Signaling Suppresses CRF Receptor-Mediated Stress Response

    OpenAIRE

    Andreas Stengel; Yvette F. Taché; Yvette F. Taché

    2017-01-01

    Corticotropin-releasing factor (CRF) is the hallmark brain peptide triggering the response to stress and mediates—in addition to the stimulation of the hypothalamus-pituitary-adrenal (HPA) axis—other hormonal, behavioral, autonomic and visceral components. Earlier reports indicate that somatostatin-28 injected intracerebroventricularly counteracts the acute stress-induced ACTH and catecholamine release. Mounting evidence now supports that activation of brain somatostatin signaling exerts a br...

  5. Receptor-mediated oral delivery of a bioencapsulated green fluorescent protein expressed in transgenic chloroplasts into the mouse circulatory system.

    Science.gov (United States)

    Limaye, Arati; Koya, Vijay; Samsam, Mohtashem; Daniell, Henry

    2006-05-01

    Oral delivery of biopharmaceutical proteins expressed in plant cells should reduce their cost of production, purification, processing, cold storage, transportation, and delivery. However, poor intestinal absorption of intact proteins is a major challenge. To overcome this limitation, we investigate here the concept of receptor-mediated oral delivery of chloroplast-expressed foreign proteins. Therefore, the transmucosal carrier cholera toxin B-subunit and green fluorescent protein (CTB-GFP), separated by a furin cleavage site, was expressed via the tobacco chloroplast genome. Polymerase chain reaction (PCR) and Southern blot analyses confirmed site-specific transgene integration and homoplasmy. Immunoblot analysis and ELISA confirmed expression of monomeric and pentameric forms of CTB-GFP, up to 21.3% of total soluble proteins. An in vitro furin cleavage assay confirmed integrity of the engineered furin cleavage site, and a GM1 binding assay confirmed the functionality of CTB-GFP pentamers. Following oral administration of CTB-GFP expressing leaf material to mice, GFP was observed in the mice intestinal mucosa, liver, and spleen in fluorescence and immunohistochemical studies, while CTB remained in the intestinal cell. This report of receptor-mediated oral delivery of a foreign protein into the circulatory system opens the door for low-cost production and delivery of human therapeutic proteins.

  6. Scavenger receptor-mediated endocytosis by sinusoidal cells in rat bone marrow

    International Nuclear Information System (INIS)

    Geoffroy, J.S.

    1987-01-01

    Endocytosis of serum albumin by sinusoidal endothelial cells in rat bone marrow was investigated initially at the ultrastructural level with subsequent biochemical investigation of the specificity mediating this event. Bovine serum albumin adsorbed to 20nm colloidal gold particles (AuBSA) was chosen as the electron microscopic probe. Morphological data strongly suggested that a receptor was involved in uptake of AuBSA. Confirmation of receptor involvement in the uptake of AuBSA by marrow sinusoidal endothelial cells was achieved utilizing an in situ isolated hind limb perfusion protocol in conjunction with unlabeled, radiolabeled, and radio-/colloidal gold labeled probes. The major findings of competition and saturation experiments were: (1) endocytosis of AuBSA was mediated by a receptor for modified/treated serum albumin; (2) endocytosis of formaldehyde-treated serum albumin was mediated by a binding site which may be the same or closely related to the site responsible for the uptake of AuBSA; and (3) endocytosis of native untreated albumin was not mediated by receptor and probably represents fluid-phase pinocitosis

  7. In vivo effect of 3,5,3'-triiodothyronine on calcium uptake in several tissues in the rat: Evidence for a physiological role for calcium as the first messenger for the prompt action of thyroid hormone at the level of the plasma membrane

    International Nuclear Information System (INIS)

    Segal, J.

    1990-01-01

    Calcium has been shown in vitro to serve as the first messenger for the rapid effect of thyroid hormone at the level of the plasma membrane. In the present study the physiological relevance of this mechanism is examined in the whole animal. To this end, the effect of T3 on 45calcium uptake and sugar 2-deoxyglucose (2-DG) uptake, an effect that requires extracellular calcium, and the influence of calcium blockers thereon were measured in ventricles, atria, diaphragm, fat, and liver in the rat. In the first three tissues, T3 produced comparable changes in 45Ca uptake and 2-DG uptake (T3 increased 2-DG uptake in fat, where 45Ca uptake was undetected, and had no effect in liver); this activity was blocked by the calcium channel blocker cadmium. The effect of T3 on 45Ca uptake, like its effect on the in vivo uptake of 2-DG described previously, was biphasic and time related; at physiological doses of 0.01 and 0.1 micrograms/100 g BW, T3 increased 45Ca uptake, whereas at greater (pharmacological) doses of 1 and 100 micrograms/100 g BW, T3 was without effect or inhibited 45Ca uptake. In ventricles and atria, the stimulatory effect of T3 on 45Ca uptake was very rapid within 2 min, at which time it was at or near maximum (50-90% above control) and then declined gradually and was not seen after 10-20 min. Of the several calcium blockers employed, verapamil (organic) and cadmium (inorganic) were found to be the most effective. Verapamil and cadmium produced a rapid, transient, and dose-related inhibition of 45Ca uptake in the tissues examined (except fat tissue where, under the experimental conditions employed, 45Ca uptake was undetected). Verapamil, given iv (200 micrograms/100 g BW) or ip (1 mg/100 g BW), reduced tissue 45Ca uptake by 50-90% within 2 or 10 min, respectively, and then its inhibitory effect diminished rapidly and was not seen after 20-30 min

  8. Vitamin D receptor-mediated control of Soggy, Wise, and Hairless gene expression in keratinocytes.

    Science.gov (United States)

    Hsieh, Jui-Cheng; Estess, Rudolf C; Kaneko, Ichiro; Whitfield, G Kerr; Jurutka, Peter W; Haussler, Mark R

    2014-02-01

    The vitamin D receptor (VDR), but not its hormonal ligand, 1,25-dihydroxyvitamin D3 (1,25D), is required for the progression of the mammalian hair cycle. We studied three genes relevant to hair cycle signaling, DKKL1 (Soggy), SOSTDC1 (Wise), and HR (Hairless), to determine whether their expression is regulated by VDR and/or its 1,25D ligand. DKKL1 mRNA was repressed 49-72% by 1,25D in primary human and CCD-1106 KERTr keratinocytes; a functional vitamin D responsive element (VDRE) was identified at -9590 bp in murine Soggy. Similarly, SOSTDC1 mRNA was repressed 41-59% by 1,25D in KERTr and primary human keratinocytes; a functional VDRE was located at -6215 bp in human Wise. In contrast, HR mRNA was upregulated 1.56- to 2.77-fold by 1,25D in primary human and KERTr keratinocytes; a VDRE (TGGTGAgtgAGGACA) consisting of an imperfect direct repeat separated by three nucleotides (DR3) was identified at -7269 bp in the human Hairless gene that mediated dramatic induction, even in the absence of 1,25D ligand. In parallel, a DR4 thyroid hormone responsive element, TGGTGAggccAGGACA, was identified at +1304 bp in the human HR gene that conferred tri-iodothyronine (T3)-independent transcriptional activation. Because the thyroid hormone receptor controls HR expression in the CNS, whereas VDR functions in concert with the HR corepressor specifically in skin, a model is proposed wherein unliganded VDR upregulates the expression of HR, the gene product of which acts as a downstream comodulator to feedback-repress DKKL1 and SOSTDC1, resulting in integration of bone morphogenic protein and Wnt signaling to drive the mammalian hair cycle and/or influencing epidermal function.

  9. Activation of Brain Somatostatin Signaling Suppresses CRF Receptor-Mediated Stress Response

    Directory of Open Access Journals (Sweden)

    Andreas Stengel

    2017-04-01

    Full Text Available Corticotropin-releasing factor (CRF is the hallmark brain peptide triggering the response to stress and mediates—in addition to the stimulation of the hypothalamus-pituitary-adrenal (HPA axis—other hormonal, behavioral, autonomic and visceral components. Earlier reports indicate that somatostatin-28 injected intracerebroventricularly counteracts the acute stress-induced ACTH and catecholamine release. Mounting evidence now supports that activation of brain somatostatin signaling exerts a broader anti-stress effect by blunting the endocrine, autonomic, behavioral (with a focus on food intake and visceral gastrointestinal motor responses through the involvement of distinct somatostatin receptor subtypes.

  10. Activation of Brain Somatostatin Signaling Suppresses CRF Receptor-Mediated Stress Response.

    Science.gov (United States)

    Stengel, Andreas; Taché, Yvette F

    2017-01-01

    Corticotropin-releasing factor (CRF) is the hallmark brain peptide triggering the response to stress and mediates-in addition to the stimulation of the hypothalamus-pituitary-adrenal (HPA) axis-other hormonal, behavioral, autonomic and visceral components. Earlier reports indicate that somatostatin-28 injected intracerebroventricularly counteracts the acute stress-induced ACTH and catecholamine release. Mounting evidence now supports that activation of brain somatostatin signaling exerts a broader anti-stress effect by blunting the endocrine, autonomic, behavioral (with a focus on food intake) and visceral gastrointestinal motor responses through the involvement of distinct somatostatin receptor subtypes.

  11. Hormone assay

    International Nuclear Information System (INIS)

    Eisentraut, A.M.

    1977-01-01

    An improved radioimmunoassay is described for measuring total triiodothyronine or total thyroxine levels in a sample of serum containing free endogenous thyroid hormone and endogenous thyroid hormone bound to thyroid hormone binding protein. The thyroid hormone is released from the protein by adding hydrochloric acid to the serum. The pH of the separated thyroid hormone and thyroid hormone binding protein is raised in the absence of a blocking agent without interference from the endogenous protein. 125 I-labelled thyroid hormone and thyroid hormone antibodies are added to the mixture, allowing the labelled and unlabelled thyroid hormone and the thyroid hormone antibody to bind competitively. This results in free thyroid hormone being separated from antibody bound thyroid hormone and thus the unknown quantity of thyroid hormone may be determined. A thyroid hormone test assay kit is described for this radioimmunoassay. It provides a 'single tube' assay which does not require blocking agents for endogenous protein interference nor an external solid phase sorption step for the separation of bound and free hormone after the competitive binding step; it also requires a minimum number of manipulative steps. Examples of the assay are given to illustrate the reproducibility, linearity and specificity of the assay. (UK)

  12. Sex Hormone Receptor Repertoire in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Gerald M. Higa

    2013-01-01

    Full Text Available Classification of breast cancer as endocrine sensitive, hormone dependent, or estrogen receptor (ER positive refers singularly to ERα. One of the oldest recognized tumor targets, disruption of ERα-mediated signaling, is believed to be the mechanistic mode of action for all hormonal interventions used in treating this disease. Whereas ERα is widely accepted as the single most important predictive factor (for response to endocrine therapy, the presence of the receptor in tumor cells is also of prognostic value. Even though the clinical relevance of the two other sex hormone receptors, namely, ERβ and the androgen receptor remains unclear, two discordant phenomena observed in hormone-dependent breast cancers could be causally related to ERβ-mediated effects and androgenic actions. Nonetheless, our understanding of regulatory molecules and resistance mechanisms remains incomplete, further compromising our ability to develop novel therapeutic strategies that could improve disease outcomes. This review focuses on the receptor-mediated actions of the sex hormones in breast cancer.

  13. Gamma interferon augments Fc gamma receptor-mediated dengue virus infection of human monocytic cells.

    OpenAIRE

    Kontny, U; Kurane, I; Ennis, F A

    1988-01-01

    It has been reported that anti-dengue antibodies at subneutralizing concentrations augment dengue virus infection of monocytic cells. This is due to the increased uptake of dengue virus in the form of virus-antibody complexes by cells via Fc gamma receptors. We analyzed the effects of recombinant human gamma interferon (rIFN-gamma) on dengue virus infection of human monocytic cells. U937 cells, a human monocytic cell line, were infected with dengue virus in the form of virus-antibody complexe...

  14. Uptake of magnetic nanoparticles into cells for cell tracking

    International Nuclear Information System (INIS)

    Becker, Christiane; Hodenius, Michael; Blendinger, Gitta; Sechi, Antonio; Hieronymus, Thomas; Mueller-Schulte, Detlef; Schmitz-Rode, Thomas; Zenke, Martin

    2007-01-01

    A challenge for future applications in nanotechnology is the functional integration of nano-sized materials into cellular structures. Here we investigated superparamagnetic Fe 3 O 4 iron oxide nanoparticles coated with a lipid bilayer for uptake into cells and for targeting subcellular compartments. It was found that magnetic nanoparticles (MNPs) are effectively taken up into cells and make cells acquire magnetic activity. Biotin-conjugated MNPs were further functionalized by binding of the fluorescent tag streptavidin-fluorescein isothiocyanate (FITC) and, following uptake into cells, shown to confer magnetic activity and fluorescence labeling. Such FITC-MNPs were localized in the lysosomal compartment of cells which suggests a receptor-mediated uptake mechanism

  15. Halothane inhibits the cholinergic-receptor-mediated influx of calcium in primary culture of bovine adrenal medulla cells

    International Nuclear Information System (INIS)

    Yashima, N.; Wada, A.; Izumi, F.

    1986-01-01

    Adrenal medulla cells are cholinoceptive cells. Stimulation of the acetylcholine receptor causes the influx of Ca to the cells, and Ca acts as the coupler of the stimulus-secretion coupling. In this study, the authors investigated the effects of halothane on the receptor-mediated influx of 45 Ca using cultured bovine adrenal medulla cells. Halothane at clinical concentrations (0.5-2%) inhibited the influx of 45 Ca caused by carbachol, with simultaneous inhibition of catecholamine secretion. The influx of 45 Ca and the secretion of catecholamines caused by K depolarization were inhibited by a large concentration of Mg, which competes with Ca at Ca channels, but not inhibited by halothane. Inhibition of the 45 Ca influx by halothane was not overcome by increase in the carbachol concentration. Inhibition of the 45 Ca influx by halothane was examined in comparison with that caused by a large concentration of Mg by the application of Scatchard analysis as the function of the external Ca concentration. Halothane decreased the maximal influx of 45 Ca without altering the apparent kinetic constant of Ca to Ca channels. On the contrary, a large concentration of Mg increased the apparent kinetic constant without altering the maximal influx of 45 Ca. Based on these findings, the authors suggest that inhibition of the 45 Ca influx by halothane was not due to the direct competitive inhibition of Ca channels, nor to the competitive antagonism of agonist-receptor interaction. As a possibility, halothane seems to inhibit the receptor-mediated activation of Ca channels through the interference of coupling between the receptor and Ca channels

  16. Reboxetine Enhances the Olanzapine-Induced Antipsychotic-Like Effect, Cortical Dopamine Outflow and NMDA Receptor-Mediated Transmission

    Science.gov (United States)

    Marcus, Monica M; Jardemark, Kent; Malmerfelt, Anna; Björkholm, Carl; Svensson, Torgny H

    2010-01-01

    Preclinical data have shown that addition of the selective norepinephrine transporter (NET) inhibitor reboxetine increases the antipsychotic-like effect of the D2/3 antagonist raclopride and, in parallel, enhances cortical dopamine output. Subsequent clinical results suggested that adding reboxetine to stable treatments with various antipsychotic drugs (APDs) may improve positive, negative and depressive symptoms in schizophrenia. In this study, we investigated in rats the effects of adding reboxetine to the second-generation APD olanzapine on: (i) antipsychotic efficacy, using the conditioned avoidance response (CAR) test, (ii) extrapyramidal side effect (EPS) liability, using a catalepsy test, (iii) dopamine efflux in the medial prefrontal cortex and the nucleus accumbens, using in vivo microdialysis in freely moving animals and (iv) cortical N-methyl--aspartate (NMDA) receptor-mediated transmission, using intracellular electrophysiological recording in vitro. Reboxetine (6 mg/kg) enhanced the suppression of CAR induced by a suboptimal dose (1.25 mg/kg), but not an optimal (2.5 mg/kg) dose of olanzapine without any concomitant catalepsy. Addition of reboxetine to the low dose of olanzapine also markedly increased cortical dopamine outflow and facilitated prefrontal NMDA receptor-mediated transmission. Our data suggest that adjunctive treatment with a NET inhibitor may enhance the therapeutic effect of low-dose olanzapine in schizophrenia without increasing EPS liability and add an antidepressant action, thus in principle allowing for a dose reduction of olanzapine with a concomitant reduction of dose-related side effects, such as EPS and weight gain. PMID:20463659

  17. Prostaglandin E2 potentiation of P2X3 receptor mediated currents in dorsal root ganglion neurons

    Directory of Open Access Journals (Sweden)

    Huang Li-Yen

    2007-08-01

    Full Text Available Abstract Prostaglandin E2 (PGE2 is a well-known inflammatory mediator that enhances the excitability of DRG neurons. Homomeric P2X3 and heteromeric P2X2/3 receptors are abundantly expressed in dorsal root ganglia (DRG neurons and participate in the transmission of nociceptive signals. The interaction between PGE2 and P2X3 receptors has not been well delineated. We studied the actions of PGE2 on ATP-activated currents in dissociated DRG neurons under voltage-clamp conditions. PGE2 had no effects on P2X2/3 receptor-mediated responses, but significantly potentiated fast-inactivating ATP currents mediated by homomeric P2X3 receptors. PGE2 exerted its action by activating EP3 receptors. To study the mechanism underlying the action of PGE2, we found that the adenylyl cyclase activator, forskolin and the membrane-permeable cAMP analogue, 8-Br-cAMP increased ATP currents, mimicking the effect of PGE2. In addition, forskolin occluded the enhancement produced by PGE2. The protein kinase A (PKA inhibitors, H89 and PKA-I blocked the PGE2 effect. In contrast, the PKC inhibitor, bisindolymaleimide (Bis did not change the potentiating action of PGE2. We further showed that PGE2 enhanced α,β-meATP-induced allodynia and hyperalgesia and the enhancement was blocked by H89. These observations suggest that PGE2 binds to EP3 receptors, resulting in the activation of cAMP/PKA signaling pathway and leading to an enhancement of P2X3 homomeric receptor-mediated ATP responses in DRG neurons.

  18. Electroacupuncture improves cerebral blood flow and attenuates moderate ischemic injury via Angiotensin II its receptors-mediated mechanism in rats.

    Science.gov (United States)

    Li, Jing; He, Jiaojun; Du, Yuanhao; Cui, Jingjun; Ma, Ying; Zhang, Xuezhu

    2014-11-11

    To investigate the effects and potential mechanism of electroacupuncture intervention on expressions of Angiotensin II and its receptors-mediated signaling pathway in experimentally induced cerebral ischemia. Totally 126 male Wistar rats were randomly divided into control group, model group and EA group. The latter two were further divided into ten subgroups (n = 6) following Middle Cerebral Artery Occlusion (MCAO). Changes in regional cerebral blood flow (rCBF) and expressions of Angiotensin II and its receptors (AT1R, AT2R), as well as effector proteins in phosphatidyl inositol signal pathway were monitored before and at different times after MCAO. MCAO-induced decline of ipsilateral rCBF was partially suppressed by electroacupuncture, and contralateral blood flow was also superior to that of model group. Angiotensin II level was remarkably elevated immediately after MCAO, while electroacupuncture group exhibited significantly lower levels at 1 to 3 h and the value was significantly increased thereafter. The enhanced expression of AT1R was partially inhibited by electroacupuncture, while increased AT2R level was further induced. Electroacupuncture stimulation attenuated and postponed the upregulated-expressions of Gq and CaM these upregulations. ELISA results showed sharply increased expressions of DAG and IP3, which were remarkably neutralized by electroacupuncture. MCAO induced significant increases in expression of Angiotensin II and its receptor-mediated signal pathway. These enhanced expressions were significantly attenuated by electroacupuncture intervention, followed by reduced vasoconstriction and improved blood supply in ischemic region, and ultimately conferred beneficial effects on cerebral ischemia.

  19. Loss of Progesterone Receptor-Mediated Actions Induce Preterm Cellular and Structural Remodeling of the Cervix and Premature Birth

    Science.gov (United States)

    Yellon, Steven M.; Dobyns, Abigail E.; Beck, Hailey L.; Kurtzman, James T.; Garfield, Robert E.; Kirby, Michael A.

    2013-01-01

    A decline in serum progesterone or antagonism of progesterone receptor function results in preterm labor and birth. Whether characteristics of premature remodeling of the cervix after antiprogestins or ovariectomy are similar to that at term was the focus of the present study. Groups of pregnant rats were treated with vehicle, a progesterone receptor antagonist (onapristone or mifepristone), or ovariectomized on day 17 postbreeding. As expected, controls given vehicle delivered at term while rats delivered preterm after progesterone receptor antagonist treatment or ovariectomy. Similar to the cervix before term, the preterm cervix of progesterone receptor antagonist-treated rats was characterized by reduced cell nuclei density, decreased collagen content and structure, as well as a greater presence of macrophages per unit area. Thus, loss of nuclear progesterone receptor-mediated actions promoted structural remodeling of the cervix, increased census of resident macrophages, and preterm birth much like that found in the cervix at term. In contrast to the progesterone receptor antagonist-induced advance in characteristics associated with remodeling, ovariectomy-induced loss of systemic progesterone did not affect hypertrophy, extracellular collagen, or macrophage numbers in the cervix. Thus, the structure and macrophage census in the cervix appear sufficient for premature ripening and birth to occur well before term. With progesterone receptors predominantly localized on cells other than macrophages, the findings suggest that interactions between cells may facilitate the loss of progesterone receptor-mediated actions as part of a final common mechanism that remodels the cervix in certain etiologies of preterm and with parturition at term. PMID:24339918

  20. DOTATOC: a powerful new tool for receptor-mediated radionuclide therapy

    International Nuclear Information System (INIS)

    Otte, A.; Jermann, E.; Behe, M.; Goetze, M.; Bucher, H.C.; Roser, H.W.; Heppeler, A.; Mueller-Brand, J.; Maecke, H.R.

    1997-01-01

    This study presents the first successful use of a peptidic vector, DOTATOC, labelled with the β-emitting radioisotope yttrium-90, for the treatment of a patient with somatostatin receptor-positive abdominal metastases of a neuroendocrine carcinoma of unknown localization. Tumour response and symptomatic relief were achieved. In addition, the new substance DOTATOC was labelled with the diagnostic chemical analogue indium-111 and studied in three patients with histopathologically verified neuroendocrine abdominal tumours for its diagnostic sensitivity and compared with the commercially available OctreoScan. In all patients the kidney-to-tumour uptake ratio (in counts per pixel) was on average 1.9-fold lower with 111 In-DOTATOC than with OctreoScan. DOTATOC could be a potential new diagnostic and therapeutic agent in the management of neuroendocrine tumours. (orig.). With 4 figs., 1 tab

  1. Insulin receptors mediate growth effects in cultured fetal neurons. I. Rapid stimulation of protein synthesis

    International Nuclear Information System (INIS)

    Heidenreich, K.A.; Toledo, S.P.

    1989-01-01

    In this study we have examined the effects of insulin on protein synthesis in cultured fetal chick neurons. Protein synthesis was monitored by measuring the incorporation of [3H]leucine (3H-leu) into trichloroacetic acid (TCA)-precipitable protein. Upon addition of 3H-leu, there was a 5-min lag before radioactivity occurred in protein. During this period cell-associated radioactivity reached equilibrium and was totally recovered in the TCA-soluble fraction. After 5 min, the incorporation of 3H-leu into protein was linear for 2 h and was inhibited (98%) by the inclusion of 10 micrograms/ml cycloheximide. After 24 h of serum deprivation, insulin increased 3H-leu incorporation into protein by approximately 2-fold. The stimulation of protein synthesis by insulin was dose dependent (ED50 = 70 pM) and seen within 30 min. Proinsulin was approximately 10-fold less potent than insulin on a molar basis in stimulating neuronal protein synthesis. Insulin had no effect on the TCA-soluble fraction of 3H-leu at any time and did not influence the uptake of [3H]aminoisobutyric acid into neurons. The isotope ratio of 3H-leu/14C-leu in the leucyl tRNA pool was the same in control and insulin-treated neurons. Analysis of newly synthesized proteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that insulin uniformly increased the incorporation of 14C-leu into all of the resolved neuronal proteins. We conclude from these data that (1) insulin rapidly stimulates overall protein synthesis in fetal neurons independent of amino acid uptake and aminoacyl tRNA precursor pools; (2) stimulation of protein synthesis is mediated by the brain subtype of insulin receptor; and (3) insulin is potentially an important in vivo growth factor for fetal central nervous system neurons

  2. Thyroid hormones and lipid phosphorus in mice

    Energy Technology Data Exchange (ETDEWEB)

    Thakare, U R; Ganatra, R D; Shah, D H [Bhabha Atomic Research Centre, Bombay (India). Radiation Medicine Centre

    1978-04-01

    In vivo studies in mice injected intravenously with /sup 125/I-triiodothyronine (T-3) showed a linear relationship between the uptake of the labelled hormone by the tissue and the lipid phosphorous content of the same tissue. However, studies with /sup 125/I-thyroxine failed to show a similar relationship between the lipid phosphorous content of the organ and the uptake of radioactive hormone by the same organ. In vitro studies using equilibrium dialysis technique with isolated lipid extracts of various organs and radioactive thyroid hormones (T-3 and T-4) did not show any relation between the lipid P and the uptake of labelled hormone. On the basis of the observed discrepancy between in vivo and in vitro studies, it is postulated that an organized lipoprotein structure at the cell membrane may be responsible for the entry of the thyroid hormones.

  3. Astrocytic β2-adrenergic receptors mediate hippocampal long-term memory consolidation

    KAUST Repository

    Gao, Virginia; Suzuki, Akinobu; Magistretti, Pierre J.; Lengacher, Sylvain; Pollonini, Gabriella; Steinman, Michael Q.; Alberini, Cristina M.

    2016-01-01

    Emotionally relevant experiences form strong and long-lasting memories by critically engaging the stress hormone/neurotransmitter noradrenaline, which mediates and modulates the consolidation of these memories. Noradrenaline acts through adrenergic receptors (ARs), of which β2- Adrenergic receptors (βARs) are of particular importance. The differential anatomical and cellular distribution of βAR subtypes in the brain suggests that they play distinct roles in memory processing, although much about their specific contributions and mechanisms of action remains to be understood. Here we show that astrocytic rather than neuronal β2ARs in the hippocampus play a key role in the consolidation of a fear-based contextual memory. These hippocampal β2ARs, but not β1ARs, are coupled to the training-dependent release of lactate from astrocytes, which is necessary for long- Term memory formation and for underlying molecular changes. This key metabolic role of astrocytic β2ARs may represent a novel target mechanism for stress-related psychopathologies and neurodegeneration.

  4. Targeting of liposomes to cells bearing nerve growth factor receptors mediated by biotinylated NGF

    International Nuclear Information System (INIS)

    Rosenberg, M.B.

    1986-01-01

    Previous studies of liposome targeting have concentrated on immunological systems, the use of ligand-receptor interactions has received little attention. The protein hormone beta-nerve growth factor (NGF) was modified by biotinylation via carboxyl group substitution (C-bio-NGF) under reaction conditions that yielded an average of 3 biotin additions per NGF subunit. NGF was also biotinylated through amino group substitution to produce derivatives with ratios of 1, 2 and 4 biotin moieties per NGF subunit (N-bio-NGF). These derivatives were compared with native NGF for their ability to compete with 125 I-NGF for binding to NGF receptors on rat pheochromocytoma (PC 12) cells at 4 0 C. C-bio-NGF was as effective as native NGF in binding to NGF receptors, while N-bio-NGF containing 1 biotin per NGF subunit was only 28% as active in binding as native NGF. C-bio-NGF, but not N-bio-NGF, mediated the specific binding of 125 I-streptavidin to PC12 cells. Biocytin-NGF, a derivative of C-bio-NGF with an extended spacer chain, was also synthesized and retained full biological and receptor binding activities. C-bio-NGF and biocytin-NGF were as effective as native NGF in a bioassay involving induction of neurite outgrowth from PC12 cells

  5. Astrocytic β2-adrenergic receptors mediate hippocampal long-term memory consolidation

    KAUST Repository

    Gao, Virginia

    2016-07-12

    Emotionally relevant experiences form strong and long-lasting memories by critically engaging the stress hormone/neurotransmitter noradrenaline, which mediates and modulates the consolidation of these memories. Noradrenaline acts through adrenergic receptors (ARs), of which β2- Adrenergic receptors (βARs) are of particular importance. The differential anatomical and cellular distribution of βAR subtypes in the brain suggests that they play distinct roles in memory processing, although much about their specific contributions and mechanisms of action remains to be understood. Here we show that astrocytic rather than neuronal β2ARs in the hippocampus play a key role in the consolidation of a fear-based contextual memory. These hippocampal β2ARs, but not β1ARs, are coupled to the training-dependent release of lactate from astrocytes, which is necessary for long- Term memory formation and for underlying molecular changes. This key metabolic role of astrocytic β2ARs may represent a novel target mechanism for stress-related psychopathologies and neurodegeneration.

  6. Phenobarbital but not diazepam reduces AMPA/Kainate receptor mediated currents and exerts opposite actions on initial seizures in the neonatal rat hippocampus

    Directory of Open Access Journals (Sweden)

    Romain eNardou

    2011-07-01

    Full Text Available Diazepam (DZP and phenobarbital (PB are extensively used as first and second line drugs to treat acute seizures in neonates and their actions are thought to be mediated by increasing the actions of GABAergic signals. Yet, their efficacy is variable with occasional failure or even aggravation of recurrent seizures questioning whether other mechanisms are not involved in their actions. We have now compared the effects of DZP and PB on ictal-like events (ILEs in an in vitro model of mirror focus (MF. Using the three-compartment chamber with the two immature hippocampi and their commissural fibers placed in 3 different compartments, kainate was applied to one hippocampus and PB or DZP to the contralateral one, either after one ILE or after many recurrent ILEs that produce an epileptogenic MF. We report that in contrast to PB, DZP aggravated propagating ILEs from the start and did not prevent the formation of MF. PB reduced and DZP increased the network driven Giant Depolarising Potentials suggesting that PB may exert additional actions that are not mediated by GABA signalling. In keeping with this, PB but not DZP reduced field potentials recorded in the presence of GABA and NMDA receptor antagonists. These effects are mediated by a direct action on AMPA/Kainate receptors since PB: i reduced AMPA/Kainate receptor mediated currents induced by focal applications of glutamate ; ii reduced the amplitude and the frequency of AMPA but not NMDA receptor mediated miniature EPSCs; iii augmented the number of AMPA receptor mediated EPSCs failures evoked by minimal stimulation. These effects persisted in MF. Therefore, PB exerts its anticonvulsive actions partly by reducing AMPA/Kainate receptors mediated EPSCs in addition to the pro-GABA effects. We suggest that PB may have advantage over DZP in the treatment of initial neonatal seizures since the additional reduction of glutamate receptors mediated signals may reduce the severity of neonatal seizures.

  7. An in vitro approach for prioritization and evaluation of chemical effects on glucocorticoid receptor mediated adipogenesis.

    Science.gov (United States)

    Hartman, Jessica K; Beames, Tyler; Parks, Bethany; Doheny, Daniel; Song, Gina; Efremenko, Alina; Yoon, Miyoung; Foley, Briana; Deisenroth, Chad; McMullen, Patrick D; Clewell, Rebecca A

    2018-05-18

    Rising obesity rates worldwide have socio-economic ramifications. While genetics, diet, and lack of exercise are major contributors to obesity, environmental factors may enhance susceptibility through disruption of hormone homeostasis and metabolic processes. The obesogen hypothesis contends that chemical exposure early in development may enhance adipocyte differentiation, thereby increasing the number of adipocytes and predisposing for obesity and metabolic disease. We previously developed a primary human adipose stem cell (hASC) assay to evaluate the effect of environmental chemicals on PPARG-dependent adipogenesis. Here, the assay was modified to determine the effects of chemicals on the glucocorticoid receptor (GR) pathway. In differentiation cocktail lacking the glucocorticoid agonist dexamethasone (DEX), hASCs do not differentiate into adipocytes. In the presence of GR agonists, adipocyte maturation was observed using phenotypic makers for lipid accumulation, adipokine secretion, and expression of key genes. To evaluate the role of environmental compounds on adipocyte differentiation, progenitor cells were treated with 19 prioritized compounds previously identified by ToxPi as having GR-dependent bioactivity, and multiplexed assays were used to confirm a GR-dependent mode of action. Five chemicals were found to be strong agonists. The assay was also modified to evaluate GR-antagonists, and 8/10 of the hypothesized antagonists inhibited adipogenesis. The in vitro bioactivity data was put into context with extrapolated human steady state concentrations (Css) and clinical exposure data (Cmax). These data support using a human adipose-derived stem cell differentiation assay to test the potential of chemicals to alter human GR-dependent adipogenesis. Copyright © 2017. Published by Elsevier Inc.

  8. Cobaltous chloride and hypoxia inhibit aryl hydrocarbon receptor-mediated responses in breast cancer cells

    International Nuclear Information System (INIS)

    Khan, Shaheen; Liu Shengxi; Stoner, Matthew; Safe, Stephen

    2007-01-01

    The aryl hydrocarbon receptor (AhR) is expressed in estrogen receptor (ER)-positive ZR-75 breast cancer cells. Treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces CYP1A1 protein and mRNA levels and also activates inhibitory AhR-ERα crosstalk associated with hormone-induced reporter gene expression. In ZR-75 cells grown under hypoxia, induction of these AhR-mediated responses by TCDD was significantly inhibited. This was not accompanied by decreased nuclear AhR levels or decreased interaction of the AhR complex with the CYP1A1 gene promoter as determined in a chromatin immunoprecipitation assay. Hypoxia-induced loss of Ah-responsiveness was not associated with induction of hypoxia-inducible factor-1α or other factors that sequester the AhR nuclear translocation (Arnt) protein, and overexpression of Arnt under hypoxia did not restore Ah-responsiveness. The p65 subunit of NFκB which inhibits AhR-mediated transactivation was not induced by hypoxia and was primarily cytosolic in ZR-75 cells grown under hypoxic and normoxic conditions. In ZR-75 cells maintained under hypoxic conditions for 24 h, BRCA1 (an enhancer of AhR-mediated transactivation in breast cancer cells) was significantly decreased and this contributed to loss of Ah-responsiveness. In cells grown under hypoxia for 6 h, BRCA1 was not decreased, but induction of CYP1A1 by TCDD was significantly decreased. Cotreatment of ZR-75 cells with TCDD plus the protein synthesis inhibitor cycloheximide for 6 h enhanced CYP1A1 expression in cells grown under hypoxia and normoxia. These results suggest that hypoxia rapidly induces protein(s) that inhibit Ah-responsiveness and these may be similar to constitutively expressed inhibitors of Ah-responsiveness (under normoxia) that are also inhibited by cycloheximide

  9. Ionotropic glutamate receptors mediate inducible defense in the water flea Daphnia pulex.

    Directory of Open Access Journals (Sweden)

    Hitoshi Miyakawa

    Full Text Available Phenotypic plasticity is the ability held in many organisms to produce different phenotypes with a given genome in response to environmental stimuli, such as temperature, nutrition and various biological interactions. It seems likely that environmental signals induce a variety of mechanistic responses that influence ontogenetic processes. Inducible defenses, in which prey animals alter their morphology, behavior and/or other traits to help protect against direct or latent predation threats, are among the most striking examples of phenotypic plasticity. The freshwater microcrustacean Daphnia pulex forms tooth-like defensive structures, "neckteeth," in response to chemical cues or signals, referred to as "kairomones," in this case released from phantom midge larvae, a predator of D. pulex. To identify factors involved in the reception and/or transmission of a kairomone, we used microarray analysis to identify genes up-regulated following a short period of exposure to the midge kairomone. In addition to identifying differentially expressed genes of unknown function, we also found significant up-regulation of genes encoding ionotropic glutamate receptors, which are known to be involved in neurotransmission in many animal species. Specific antagonists of these receptors strongly inhibit the formation of neckteeth in D. pulex, although agonists did not induce neckteeth by themselves, indicating that ionotropic glutamate receptors are necessary but not sufficient for early steps of neckteeth formation in D. pulex. Moreover, using co-exposure of D. pulex to antagonists and juvenile hormone (JH, which physiologically mediates neckteeth formation, we found evidence suggesting that the inhibitory effect of antagonists is not due to direct inhibition of JH synthesis/secretion. Our findings not only provide a candidate molecule required for the inducible defense response in D. pulex, but also will contribute to the understanding of complex mechanisms

  10. Bovine lactoferrin counteracts Toll-like receptor mediated activation signals in antigen presenting cells.

    Directory of Open Access Journals (Sweden)

    Patrizia Puddu

    Full Text Available Lactoferrin (LF, a key element in mammalian immune system, plays pivotal roles in host defence against infection and excessive inflammation. Its protective effects range from direct antimicrobial activities against a large panel of microbes, including bacteria, viruses, fungi and parasites, to antinflammatory and anticancer activities. In this study, we show that monocyte-derived dendritic cells (MD-DCs generated in the presence of bovine LF (bLF fail to undergo activation by up-modulating CD83, co-stimulatory and major histocompatibility complex molecules, and cytokine/chemokine secretion. Moreover, these cells are weak activators of T cell proliferation and retain antigen uptake activity. Consistent with an impaired maturation, bLF-MD-DC primed T lymphocytes exhibit a functional unresponsiveness characterized by reduced expression of CD154 and impaired expression of IFN-γ and IL-2. The observed imunosuppressive effects correlate with an increased expression of molecules with negative regulatory functions (i.e. immunoglobulin-like transcript 3 and programmed death ligand 1, indoleamine 2,3-dioxygenase, and suppressor of cytokine signaling-3. Interestingly, bLF-MD-DCs produce IL-6 and exhibit constitutive signal transducer and activator of transcription 3 activation. Conversely, bLF exposure of already differentiated MD-DCs completely fails to induce IL-6, and partially inhibits Toll-like receptor (TLR agonist-induced activation. Cell-specific differences in bLF internalization likely account for the distinct response elicited by bLF in monocytes versus immature DCs, providing a mechanistic base for its multiple effects. These results indicate that bLF exerts a potent anti-inflammatory activity by skewing monocyte differentiation into DCs with impaired capacity to undergo activation and to promote Th1 responses. Overall, these bLF-mediated effects may represent a strategy to block excessive DC activation upon TLR-induced inflammation, adding

  11. Prenatal Alcohol Exposure Increases Histamine H3 Receptor-Mediated Inhibition of Glutamatergic Neurotransmission in Rat Dentate Gyrus.

    Science.gov (United States)

    Varaschin, Rafael K; Allen, Nyika A; Rosenberg, Martina J; Valenzuela, C Fernando; Savage, Daniel D

    2018-02-01

    We have reported that prenatal alcohol exposure (PAE)-induced deficits in dentate gyrus, long-term potentiation (LTP), and memory are ameliorated by the histamine H 3 receptor inverse agonist ABT-239. Curiously, ABT-239 did not enhance LTP or memory in control offspring. Here, we initiated an investigation of how PAE alters histaminergic neurotransmission in the dentate gyrus and other brain regions employing combined radiohistochemical and electrophysiological approaches in vitro to examine histamine H 3 receptor number and function. Long-Evans rat dams voluntarily consumed either a 0% or 5% ethanol solution 4 hours each day throughout gestation. This pattern of drinking, which produces a mean peak maternal serum ethanol concentration of 60.8 ± 5.8 mg/dl, did not affect maternal weight gain, litter size, or offspring birthweight. Radiohistochemical studies in adult offspring revealed that specific [ 3 H]-A349821 binding to histamine H 3 receptors was not different in PAE rats compared to controls. However, H 3 receptor-mediated G i /G o protein-effector coupling, as measured by methimepip-stimulated [ 35 S]-GTPγS binding, was significantly increased in cerebral cortex, cerebellum, and dentate gyrus of PAE rats compared to control. A LIGAND analysis of detailed methimepip concentration-response curves in dentate gyrus indicated that PAE significantly elevates receptor-effector coupling by a lower affinity H 3 receptor population without significantly altering the affinities of H 3 receptor subpopulations. In agreement with the [ 35 S]-GTPγS studies, a similar range of methimepip concentrations also inhibited electrically evoked field excitatory postsynaptic potential responses and increased paired-pulse ratio, a measure of decreased glutamate release, to a significantly greater extent in dentate gyrus slices from PAE rats than in controls. These results suggest that a PAE-induced elevation in H 3 receptor-mediated inhibition of glutamate release from

  12. Down-regulation of parathyroid hormone (PTH) receptors in cultured bone cells is associated with agonist-specific intracellular processing of PTH-receptor complexes.

    Science.gov (United States)

    Teitelbaum, A P; Silve, C M; Nyiredy, K O; Arnaud, C D

    1986-02-01

    that the attenuation of PTH stimulation of cAMP production in treated bone cells may be, at least in part, due to receptor-mediated endocytosis of the hormone.

  13. The overexpressed human 46-kDa mannose 6-phosphate receptor mediates endocytosis and sorting of β-glucuronidase

    International Nuclear Information System (INIS)

    Watanabe, H.; Grubb, J.H.; Sly, W.S.

    1990-01-01

    The authors studied the function of the human small (46-kDa) mannose 6-phosphate receptor (SMPR) in transfected mouse L cells that do not express the larger insulin-like growth factor II/mannose 6-phosphate receptor. Cells overexpressing human SMPR were studied for enzyme binding to cell surface receptors, for binding to intracellular receptors in permeabilized cells, and for receptor-mediated endocytosis of recombinant human β-glucuronidase. Specific binding to human SMPR in permeabilized cells showed a pH optimum between pH 6.0 and pH 6.5. Binding was significant in the present of EDTA but was enhanced by added divalent cations. Up to 2.3% of the total functional receptor could be detected on the cell surface by enzyme binding. They present experiments showing that at very high levels of overexpression, and at pH 6.5, human SMPR mediated the endocytosis of β-glucuronidase. At pH 7.5, the rate of endocytosis was only 14% the rate seen at pH 6.5. Cells overexpressing human SMPR also showed reduced secretion of newly synthesized β-glucuronidase when compared to cells transfected with vector only, suggesting that overexpressed human SMPR can participate in sorting of newly synthesized β-glucuronidase and partially correct the sorting defect in mouse L cells that do not express the insulin-like growth factor II/mannose 6-phosphate receptor

  14. The Influence of Receptor-Mediated Interactions on Reaction-Diffusion Mechanisms of Cellular Self-organisation

    KAUST Repository

    Klika, Václav

    2011-11-10

    Understanding the mechanisms governing and regulating self-organisation in the developing embryo is a key challenge that has puzzled and fascinated scientists for decades. Since its conception in 1952 the Turing model has been a paradigm for pattern formation, motivating numerous theoretical and experimental studies, though its verification at the molecular level in biological systems has remained elusive. In this work, we consider the influence of receptor-mediated dynamics within the framework of Turing models, showing how non-diffusing species impact the conditions for the emergence of self-organisation. We illustrate our results within the framework of hair follicle pre-patterning, showing how receptor interaction structures can be constrained by the requirement for patterning, without the need for detailed knowledge of the network dynamics. Finally, in the light of our results, we discuss the ability of such systems to pattern outside the classical limits of the Turing model, and the inherent dangers involved in model reduction. © 2011 Society for Mathematical Biology.

  15. Rac1 switching at the right time and location is essential for Fcγ receptor-mediated phagosome formation.

    Science.gov (United States)

    Ikeda, Yuka; Kawai, Katsuhisa; Ikawa, Akira; Kawamoto, Kyoko; Egami, Youhei; Araki, Nobukazu

    2017-08-01

    Lamellipodia are sheet-like cell protrusions driven by actin polymerization mainly through Rac1, a GTPase molecular switch. In Fcγ receptor-mediated phagocytosis of IgG-opsonized erythrocytes (IgG-Es), Rac1 activation is required for lamellipodial extension along the surface of IgG-Es. However, the significance of Rac1 deactivation in phagosome formation is poorly understood. Our live-cell imaging and electron microscopy revealed that RAW264 macrophages expressing a constitutively active Rac1 mutant showed defects in phagocytic cup formation, while lamellipodia were formed around IgG-Es. Because activated Rac1 reduced the phosphorylation levels of myosin light chains, failure of the cup formation is probably due to inhibition of actin/myosin II contractility. Reversible photo-manipulation of the Rac1 switch in macrophages fed with IgG-Es could phenocopy two lamellipodial motilities: outward-extension and cup-constriction by Rac1 ON and OFF, respectively. In conjunction with fluorescence resonance energy transfer imaging of Rac1 activity, we provide a novel mechanistic model of phagosome formation spatiotemporally controlled by Rac1 switching within a phagocytic cup. © 2017. Published by The Company of Biologists Ltd.

  16. ZFAT plays critical roles in peripheral T cell homeostasis and its T cell receptor-mediated response

    International Nuclear Information System (INIS)

    Doi, Keiko; Fujimoto, Takahiro; Okamura, Tadashi; Ogawa, Masahiro; Tanaka, Yoko; Mototani, Yasumasa; Goto, Motohito; Ota, Takeharu; Matsuzaki, Hiroshi; Kuroki, Masahide; Tsunoda, Toshiyuki; Sasazuki, Takehiko; Shirasawa, Senji

    2012-01-01

    Highlights: ► We generated Cd4-Cre-mediated T cell-specific Zfat-deficient mice. ► Zfat-deficiency leads to reduction in the number of the peripheral T cells. ► Impaired T cell receptor-mediated response in Zfat-deficient peripheral T cells. ► Decreased expression of IL-7Rα, IL-2Rα and IL-2 in Zfat-deficient peripheral T cells. ► Zfat plays critical roles in peripheral T cell homeostasis. -- Abstract: ZFAT, originally identified as a candidate susceptibility gene for autoimmune thyroid disease, has been reported to be involved in apoptosis, development and primitive hematopoiesis. Zfat is highly expressed in T- and B-cells in the lymphoid tissues, however, its physiological function in the immune system remains totally unknown. Here, we generated the T cell-specific Zfat-deficient mice and demonstrated that Zfat-deficiency leads to a remarkable reduction in the number of the peripheral T cells. Intriguingly, a reduced expression of IL-7Rα and the impaired responsiveness to IL-7 for the survival were observed in the Zfat-deficient T cells. Furthermore, a severe defect in proliferation and increased apoptosis in the Zfat-deficient T cells following T cell receptor (TCR) stimulation was observed with a reduced IL-2Rα expression as well as a reduced IL-2 production. Thus, our findings reveal that Zfat is a critical regulator in peripheral T cell homeostasis and its TCR-mediated response.

  17. Hormone action. Part I. Peptide hormones

    International Nuclear Information System (INIS)

    Birnbaumer, L.; O'Malley, B.W.

    1985-01-01

    The major sections of this book on the hormonal action of peptide hormones cover receptor assays, identification of receptor proteins, methods for identification of internalized hormones and hormone receptors, preparation of hormonally responsive cells and cell hybrids, purification of membrane receptors and related techniques, assays of hormonal effects and related functions, and antibodies in hormone action

  18. Stimulation of accumbal GABAA receptors inhibits delta2-, but not delta1-, opioid receptor-mediated dopamine efflux in the nucleus accumbens of freely moving rats.

    Science.gov (United States)

    Aono, Yuri; Kiguchi, Yuri; Watanabe, Yuriko; Waddington, John L; Saigusa, Tadashi

    2017-11-15

    The nucleus accumbens contains delta-opioid receptors that may reduce inhibitory neurotransmission. Reduction in GABA A receptor-mediated inhibition of accumbal dopamine release due to delta-opioid receptor activation should be suppressed by stimulating accumbal GABA A receptors. As delta-opioid receptors are divided into delta2- and delta1-opioid receptors, we analysed the effects of the GABA A receptor agonist muscimol on delta2- and delta1-opioid receptor-mediated accumbal dopamine efflux in freely moving rats using in vivo microdialysis. Drugs were administered intracerebrally through the dialysis probe. Doses of compounds indicate total amount administered (mol) during 25-50min infusions. The delta2-opioid receptor agonist deltorphin II (25.0nmol)- and delta1-opioid receptor agonist DPDPE (5.0nmol)-induced increases in dopamine efflux were inhibited by the delta2-opioid receptor antagonist naltriben (1.5nmol) and the delta1-opioid receptor antagonist BNTX (150.0pmol), respectively. Muscimol (250.0pmol) inhibited deltorphin II (25.0nmol)-induced dopamine efflux. The GABA A receptor antagonist bicuculline (50.0pmol), which failed to affect deltorphin II (25.0nmol)-induced dopamine efflux, counteracted the inhibitory effect of muscimol on deltorphin II-induced dopamine efflux. Neither muscimol (250.0pmol) nor bicuculline (50.0 and 500.0pmol) altered DPDPE (5.0nmol)-induced dopamine efflux. The present results show that reduction in accumbal GABA A receptor-mediated inhibition of dopaminergic activity is necessary to produce delta2-opioid receptor-induced increase in accumbal dopamine efflux. This study indicates that activation of delta2- but not delta1-opioid receptors on the cell bodies and/or terminals of accumbal GABAergic interneurons inhibits GABA release and, accordingly, decreases GABA A receptor-mediated inhibition of dopaminergic terminals, resulting in enhanced accumbal dopamine efflux. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Steroid Hormone Receptor Signals as Prognosticators for Urothelial Tumor

    Directory of Open Access Journals (Sweden)

    Hiroki Ide

    2015-01-01

    Full Text Available There is a substantial amount of preclinical or clinical evidence suggesting that steroid hormone receptor-mediated signals play a critical role in urothelial tumorigenesis and tumor progression. These receptors include androgen receptor, estrogen receptors, glucocorticoid receptor, progesterone receptor, vitamin D receptor, retinoid receptors, peroxisome proliferator-activated receptors, and others including orphan receptors. In particular, studies using urothelial cancer tissue specimens have demonstrated that elevated or reduced expression of these receptors as well as alterations of their upstream or downstream pathways correlates with patient outcomes. This review summarizes and discusses available data suggesting that steroid hormone receptors and related signals serve as biomarkers for urothelial carcinoma and are able to predict tumor recurrence or progression.

  20. Ah receptor mediated suppression of the antibody response in mice is primarily dependent on the Ah phenotype of lymphoid tissue

    International Nuclear Information System (INIS)

    Silkworth, J.B.; Antrim, L.A.; Sack, G.

    1986-01-01

    Halogenated aromatic hydrocarbons act through the aromatic hydrocarbon (Ah) receptor in mice to produce a series of toxic effects of the immune system. The receptor protein is a product of the Ah gene locus. Ah responsive (Ahb/Ahb) mice express a high affinity receptor in both lymphoid and nonlymphoid tissues whereas nonresponsive Ahd/Ahd mice express a poor affinity receptor. To determine the role of the Ah receptor of lymphoid tissue relative to that of nonlymphoid tissue in the induction of immune impairment, bone marrow was used to reconstitute lethally irradiated mice of the same or opposite Ah phenotype. All mice were given 3,3',4,4'-tetrachlorobiphenyl (35 and 350 mumol/kg) ip 2 days before immunization with sheep erythrocytes (SRBC). The immune response to this T dependent antigen and organ weights were determined 5 or 7 days later in normal or chimeric mice, respectively. Monoclonal Lyt 1.1 and Lyt 1.2 antibodies were used to establish the origin of the cells which repopulated the chimeric thymuses. The immune responses of both BALB/cBy (Ahb/Ahb) and the BALB/cBy X DBA/2 hybrid, CByD2F1 (Ahb/Ahd), were significantly suppressed but DBA/2 mice were unaffected. The immune responses of chimeric BALB/cBy----BALB/cBy and BALB/cBy----DBA/2 (donor----recipient) mice were also significantly suppressed and thymic atrophy was observed in both cases. The serum anti-SRBC antibody titers of DBA/2----BALB/cBy chimeras were also significantly decreased although not to the same extent as in BALB/cBy----DBA/2 mice. Chimeric DBA/2----DBA/2 mice were not affected. These results indicate that the sensitivity to Ah receptor mediated suppression of the antibody response is primarily determined by the Ah phenotype of the lymphoid tissue

  1. The brain cytoplasmic RNA BC1 regulates dopamine D2 receptor-mediated transmission in the striatum.

    Science.gov (United States)

    Centonze, Diego; Rossi, Silvia; Napoli, Ilaria; Mercaldo, Valentina; Lacoux, Caroline; Ferrari, Francesca; Ciotti, Maria Teresa; De Chiara, Valentina; Prosperetti, Chiara; Maccarrone, Mauro; Fezza, Filomena; Calabresi, Paolo; Bernardi, Giorgio; Bagni, Claudia

    2007-08-15

    Dopamine D(2) receptor (D(2)DR)-mediated transmission in the striatum is remarkably flexible, and changes in its efficacy have been heavily implicated in a variety of physiological and pathological conditions. Although receptor-associated proteins are clearly involved in specific forms of synaptic plasticity, the molecular mechanisms regulating the sensitivity of D(2) receptors in this brain area are essentially obscure. We have studied the physiological responses of the D(2)DR stimulations in mice lacking the brain cytoplasmic RNA BC1, a small noncoding dendritically localized RNA that is supposed to play a role in mRNA translation. We show that the efficiency of D(2)-mediated transmission regulating striatal GABA synapses is under the control of BC1 RNA, through a negative influence on D(2) receptor protein level affecting the functional pool of receptors. Ablation of the BC1 gene did not result in widespread dysregulation of synaptic transmission, because the sensitivity of cannabinoid CB(1) receptors was intact in the striatum of BC1 knock-out (KO) mice despite D(2) and CB(1) receptors mediated similar electrophysiological actions. Interestingly, the fragile X mental retardation protein FMRP, one of the multiple BC1 partners, is not involved in the BC1 effects on the D(2)-mediated transmission. Because D(2)DR mRNA is apparently equally translated in the BC1-KO and wild-type mice, whereas the protein level is higher in BC1-KO mice, we suggest that BC1 RNA controls D(2)DR indirectly, probably regulating translation of molecules involved in D(2)DR turnover and/or stability.

  2. Testin, a novel binding partner of the calcium-sensing receptor, enhances receptor-mediated Rho-kinase signalling

    International Nuclear Information System (INIS)

    Magno, Aaron L.; Ingley, Evan; Brown, Suzanne J.; Conigrave, Arthur D.; Ratajczak, Thomas; Ward, Bryan K.

    2011-01-01

    Highlights: → A yeast two-hybrid screen revealed testin bound to the calcium-sensing receptor. → The second zinc finger of LIM domain 1 of testin is critical for interaction. → Testin bound to a region of the receptor tail important for cell signalling. → Testin and receptor interaction was confirmed in mammalian (HEK293) cells. → Overexpression of testin enhanced receptor-mediated Rho signalling in HEK293 cells. -- Abstract: The calcium-sensing receptor (CaR) plays an integral role in calcium homeostasis and the regulation of other cellular functions including cell proliferation and cytoskeletal organisation. The multifunctional nature of the CaR is manifested through ligand-dependent stimulation of different signalling pathways that are also regulated by partner binding proteins. Following a yeast two-hybrid library screen using the intracellular tail of the CaR as bait, we identified several novel binding partners including the focal adhesion protein, testin. Testin has not previously been shown to interact with cell surface receptors. The sites of interaction between the CaR and testin were mapped to the membrane proximal region of the receptor tail and the second zinc-finger of LIM domain 1 of testin, the integrity of which was found to be critical for the CaR-testin interaction. The CaR-testin association was confirmed in HEK293 cells by coimmunoprecipitation and confocal microscopy studies. Ectopic expression of testin in HEK293 cells stably expressing the CaR enhanced CaR-stimulated Rho activity but had no effect on CaR-stimulated ERK signalling. These results suggest an interplay between the CaR and testin in the regulation of CaR-mediated Rho signalling with possible effects on the cytoskeleton.

  3. ZFAT plays critical roles in peripheral T cell homeostasis and its T cell receptor-mediated response

    Energy Technology Data Exchange (ETDEWEB)

    Doi, Keiko [Department of Cell Biology, Faculty of Medicine, Fukuoka University, Fukuoka (Japan); Central Research Institute for Advanced Molecular Medicine, Fukuoka University, Fukuoka (Japan); Central Research Institute of Life Sciences for the Next Generation of Women Scientists, Fukuoka University, Fukuoka (Japan); Fujimoto, Takahiro [Department of Cell Biology, Faculty of Medicine, Fukuoka University, Fukuoka (Japan); Central Research Institute for Advanced Molecular Medicine, Fukuoka University, Fukuoka (Japan); Okamura, Tadashi [Division of Animal Models, Department of Infectious Diseases, Research Institute, National Center for Global Health and Medicine, Tokyo (Japan); Ogawa, Masahiro [Central Research Institute for Advanced Molecular Medicine, Fukuoka University, Fukuoka (Japan); Tanaka, Yoko [Department of Cell Biology, Faculty of Medicine, Fukuoka University, Fukuoka (Japan); Mototani, Yasumasa; Goto, Motohito [Division of Animal Models, Department of Infectious Diseases, Research Institute, National Center for Global Health and Medicine, Tokyo (Japan); Ota, Takeharu; Matsuzaki, Hiroshi [Department of Cell Biology, Faculty of Medicine, Fukuoka University, Fukuoka (Japan); Kuroki, Masahide [Central Research Institute for Advanced Molecular Medicine, Fukuoka University, Fukuoka (Japan); Tsunoda, Toshiyuki [Department of Cell Biology, Faculty of Medicine, Fukuoka University, Fukuoka (Japan); Central Research Institute for Advanced Molecular Medicine, Fukuoka University, Fukuoka (Japan); Sasazuki, Takehiko [Institute for Advanced Study, Kyushu University, Fukuoka (Japan); Shirasawa, Senji, E-mail: sshirasa@fukuoka-u.ac.jp [Department of Cell Biology, Faculty of Medicine, Fukuoka University, Fukuoka (Japan); Central Research Institute for Advanced Molecular Medicine, Fukuoka University, Fukuoka (Japan)

    2012-08-17

    Highlights: Black-Right-Pointing-Pointer We generated Cd4-Cre-mediated T cell-specific Zfat-deficient mice. Black-Right-Pointing-Pointer Zfat-deficiency leads to reduction in the number of the peripheral T cells. Black-Right-Pointing-Pointer Impaired T cell receptor-mediated response in Zfat-deficient peripheral T cells. Black-Right-Pointing-Pointer Decreased expression of IL-7R{alpha}, IL-2R{alpha} and IL-2 in Zfat-deficient peripheral T cells. Black-Right-Pointing-Pointer Zfat plays critical roles in peripheral T cell homeostasis. -- Abstract: ZFAT, originally identified as a candidate susceptibility gene for autoimmune thyroid disease, has been reported to be involved in apoptosis, development and primitive hematopoiesis. Zfat is highly expressed in T- and B-cells in the lymphoid tissues, however, its physiological function in the immune system remains totally unknown. Here, we generated the T cell-specific Zfat-deficient mice and demonstrated that Zfat-deficiency leads to a remarkable reduction in the number of the peripheral T cells. Intriguingly, a reduced expression of IL-7R{alpha} and the impaired responsiveness to IL-7 for the survival were observed in the Zfat-deficient T cells. Furthermore, a severe defect in proliferation and increased apoptosis in the Zfat-deficient T cells following T cell receptor (TCR) stimulation was observed with a reduced IL-2R{alpha} expression as well as a reduced IL-2 production. Thus, our findings reveal that Zfat is a critical regulator in peripheral T cell homeostasis and its TCR-mediated response.

  4. Stress-induced release of anterior pituitary hormones: Effect of H3 receptor-mediated inhibition of histaminergic activity or posterior hypothalamic lesion

    DEFF Research Database (Denmark)

    Knigge, U.; Søe-Jensen, P.; Jørgensen, Henrik

    1999-01-01

    Histamine receptors, corticotropin, *Gb-endorphin, prolactin, adrenal steroids, stress, endotoxin, serotonin......Histamine receptors, corticotropin, *Gb-endorphin, prolactin, adrenal steroids, stress, endotoxin, serotonin...

  5. Hormone Data

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Hormones quantified from marine mammal and sea turtle tissue provide information about the status of each animal sampled, including its sex, reproductive status and...

  6. Hormone Therapy

    Science.gov (United States)

    ... it also can be a sign of endometrial cancer. All bleeding after menopause should be evaluated. Other side effects reported by women who take hormone therapy include fluid retention and breast soreness. This soreness usually lasts for a short ...

  7. Anti-idiotypic antibody: A new strategy for the development of a growth hormone receptor antagonist.

    Science.gov (United States)

    Lan, Hainan; Zheng, Xin; Khan, Muhammad Akram; Li, Steven

    2015-11-01

    In general, traditional growth hormone receptor antagonist can be divided into two major classes: growth hormone (GH) analogues and anti-growth hormone receptor (GHR) antibodies. Herein, we tried to explore a new class of growth hormone receptor (GHR) antagonist that may have potential advantages over the traditional antagonists. For this, we developed a monoclonal anti-idiotypic antibody growth hormone, termed CG-86. A series of experiments were conducted to characterize and evaluate this antibody, and the results from a competitive receptor-binding assay, Enzyme Linked Immunosorbent Assays (ELISA) and epitope mapping demonstrate that CG-86 behaved as a typical Ab2β. Next, we examined its antagonistic activity using in vitro cell models, and the results showed that CG-86 could effectively inhibit growth hormone receptor-mediated signalling and effectively inhibit growth hormone-induced Ba/F3-GHR638 proliferation. In summary, these studies show that an anti-idiotypic antibody (CG-86) has promise as a novel growth hormone receptor antagonist. Furthermore, the current findings also suggest that anti-idiotypic antibody may represent a novel strategy to produce a new class of growth hormone receptor antagonist, and this strategy may be applied with other cytokines or growth factors. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Dopamine D2 receptors mediate two-odor discrimination and reversal learning in C57BL/6 mice

    Directory of Open Access Journals (Sweden)

    Grandy David K

    2004-04-01

    Full Text Available Abstract Background Dopamine modulation of neuronal signaling in the frontal cortex, midbrain, and striatum is essential for processing and integrating diverse external sensory stimuli and attaching salience to environmental cues that signal causal relationships, thereby guiding goal-directed, adaptable behaviors. At the cellular level, dopamine signaling is mediated through D1-like or D2-like receptors. Although a role for D1-like receptors in a variety of goal-directed behaviors has been identified, an explicit involvement of D2 receptors has not been clearly established. To determine whether dopamine D2 receptor-mediated signaling contributes to associative and reversal learning, we compared C57Bl/6J mice that completely lack functional dopamine D2 receptors to wild-type mice with respect to their ability to attach appropriate salience to external stimuli (stimulus discrimination and disengage from inappropriate behavioral strategies when reinforcement contingencies change (e.g. reversal learning. Results Mildly food-deprived female wild-type and dopamine D2 receptor deficient mice rapidly learned to retrieve and consume visible food reinforcers from a small plastic dish. Furthermore, both genotypes readily learned to dig through the same dish filled with sterile sand in order to locate a buried food pellet. However, the dopamine D2 receptor deficient mice required significantly more trials than wild-type mice to discriminate between two dishes, each filled with a different scented sand, and to associate one of the two odors with the presence of a reinforcer (food. In addition, the dopamine D2 receptor deficient mice repeatedly fail to alter their response patterns during reversal trials where the reinforcement rules were inverted. Conclusions Inbred C57Bl/6J mice that develop in the complete absence of functional dopamine D2 receptors are capable of olfaction but display an impaired ability to acquire odor-driven reinforcement contingencies

  9. Hypersensitivity to thromboxane receptor mediated cerebral vasomotion and CBF oscillations during acute NO-deficiency in rats.

    Directory of Open Access Journals (Sweden)

    Béla Horváth

    Full Text Available BACKGROUND: Low frequency (4-12 cpm spontaneous fluctuations of the cerebrovascular tone (vasomotion and oscillations of the cerebral blood flow (CBF have been reported in diseases associated with endothelial dysfunction. Since endothelium-derived nitric oxide (NO suppresses constitutively the release and vascular effects of thromboxane A(2 (TXA(2, NO-deficiency is often associated with activation of thromboxane receptors (TP. In the present study we hypothesized that in the absence of NO, overactivation of the TP-receptor mediated cerebrovascular signaling pathway contributes to the development of vasomotion and CBF oscillations. METHODOLOGY/PRINCIPAL FINDINGS: Effects of pharmacological modulation of TP-receptor activation and its downstream signaling pathway have been investigated on CBF oscillations (measured by laser-Doppler flowmetry in anesthetized rats and vasomotion (measured by isometric tension recording in isolated rat middle cerebral arteries, MCAs both under physiological conditions and after acute inhibition of NO synthesis. Administration of the TP-receptor agonist U-46619 (1 µg/kg i.v. to control animals failed to induce any changes of the systemic or cerebral circulatory parameters. Inhibition of the NO synthesis by nitro-L-arginine methyl ester (L-NAME, 100 mg/kg i.v. resulted in increased mean arterial blood pressure and a decreased CBF accompanied by appearance of CBF-oscillations with a dominant frequency of 148±2 mHz. U-46619 significantly augmented the CBF-oscillations induced by L-NAME while inhibition of endogenous TXA(2 synthesis by ozagrel (10 mg/kg i.v. attenuated it. In isolated MCAs U-46619 in a concentration of 100 nM, which induced weak and stable contraction under physiological conditions, evoked sustained vasomotion in the absence of NO, which effect could be completely reversed by inhibition of Rho-kinase by 10 µM Y-27632. CONCLUSION/SIGNIFICANCE: These results suggest that hypersensitivity of the TP

  10. Cellular uptake of nanoparticles as determined by particle properties, experimental conditions, and cell type.

    Science.gov (United States)

    Kettler, Katja; Veltman, Karin; van de Meent, Dik; van Wezel, Annemarie; Hendriks, A Jan

    2014-03-01

    The increased application of nanoparticles (NPs) is increasing the risk of their release into the environment. Although many toxicity studies have been conducted, the environmental risk is difficult to estimate, because uptake mechanisms are often not determined in toxicity studies. In the present study, the authors review dominant uptake mechanisms of NPs in cells, as well as the effect of NP properties, experimental conditions, and cell type on NP uptake. Knowledge of NP uptake is crucial for risk assessment and is essential to predict the behavior of NPs based on their physical-chemical properties. Important uptake mechanisms for eukaryotic cells are macropinocytosis, receptor-mediated endocytosis, and phagocytosis in specialized mammalian cells. The studies reviewed demonstrate that uptake into nonphagocytic cells depends strongly on NP size, with an uptake optimum at an NP diameter of approximately 50 nm. Increasing surface charges, either positive or negative, have been shown to increase particle uptake in comparison with uncharged NPs. Another important factor is the degree of (homo-) aggregation. Results regarding shape have been ambiguous. Difficulties in the production of NPs, with 1 property changed at a time, call for a full characterization of NP properties. Only then will it be possible to draw conclusions as to which property affected the uptake. © 2013 SETAC.

  11. Uptake of low density lipoproteins by the hamster lung. Interactions with capillary endothelium

    International Nuclear Information System (INIS)

    Nistor, A.; Simionescu, M.

    1986-01-01

    The mechanism by which the circulating low density lipoproteins (LDL) contribute to the lung surfactant cholesterol was investigated by perfusing the hamster lung in situ with LDL either radiolabeled or coupled to gold, or both. Part of [ 125 I]-LDL and [ 3 H]-cholesterol LDL were taken up by a specific process which was time- and concentration-dependent and reached saturation within 20 to 30 min of perfusion. Competition experiments and removal of receptor-bound LDL by heparin suggested that about 50% of LDL uptake is receptor-independent. Experiments using double labeled LDL showed a preferential uptake of 3 H-cholesterol versus 125 I by the lung both in situ and in vivo. LDL-gold particles (LDL-Au), recirculated through the isolated lung, bound to the endothelial luminal plasma membrane and to features potentially involved in receptor-mediated endocytosis (coated pits, coated vesicles, lysosomelike structures) and in transcytosis (plasmalemmal vesicles). The results suggest that LDL uptake by the lung takes place by both receptor-mediated and receptor-independent mechanisms. Cholesterol may be in part transferred to the lung without the apoprotein moiety; the alveolar capillary endothelium appears to be the first monitor of this complex process

  12. Cellular uptake of folate-conjugated lipophilic superparamagnetic iron oxide nanoparticles

    International Nuclear Information System (INIS)

    Woo, Kyoungja; Moon, Jihyung; Choi, Kyu-Sil; Seong, Tae-Yeon; Yoon, Kwon-Ha

    2009-01-01

    We prepared five folate-conjugated lipophilic superparamagnetic iron oxide nanoparticles (F 5 -Liposuperparamagnetic iron oxide nanoparticles(SPIONs), 5.5 and 11 nm) and investigated their cellular uptake with KB cells, which is one of the representative folate-receptor over-expressing human epidermoid carcinoma cells, using MRI. The cellular uptake tests with the respective 5.5 and 11 nm F 5 -LipoSPIONs at a fixed particle concentration showed appreciable amount of receptor-mediated uptakes and the specificity was higher in 5.5 nm SPIONs, due to its higher folic acid (FA) density, without inhibition. However, the numbers of the particles taken up under FA inhibition were similar, irrespective of their sizes.

  13. Cellular uptake of folate-conjugated lipophilic superparamagnetic iron oxide nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Woo, Kyoungja [Nano-Materials Research Center, Korea Institute of Science and Technology, P. O. Box 131, Cheongryang, Seoul 130-650 (Korea, Republic of)], E-mail: kjwoo@kist.re.kr; Moon, Jihyung [Nano-Materials Research Center, Korea Institute of Science and Technology, P. O. Box 131, Cheongryang, Seoul 130-650 (Korea, Republic of); Department of Materials Science and Engineering, Korea University, 5-1, Anam-Dong, Sungbook-Ku, Seoul, 136-713 (Korea, Republic of); Choi, Kyu-Sil [Division of Molecular Imaging, Samsung Biomedical Research Institute, Samsung Medical Center, 50 Ilwon-Dong, Kangnam-Ku, Seoul 135-710 (Korea, Republic of); Seong, Tae-Yeon [Department of Materials Science and Engineering, Korea University, 5-1, Anam-Dong, Sungbook-Ku, Seoul, 136-713 (Korea, Republic of); Yoon, Kwon-Ha [Institute for Radiological Imaging Science, Wonkwang University School of Medicine, 344-2, Shinyong, Iksan, Jeonbuk 570-749 (Korea, Republic of)

    2009-05-15

    We prepared five folate-conjugated lipophilic superparamagnetic iron oxide nanoparticles (F{sub 5}-Liposuperparamagnetic iron oxide nanoparticles(SPIONs), 5.5 and 11 nm) and investigated their cellular uptake with KB cells, which is one of the representative folate-receptor over-expressing human epidermoid carcinoma cells, using MRI. The cellular uptake tests with the respective 5.5 and 11 nm F{sub 5}-LipoSPIONs at a fixed particle concentration showed appreciable amount of receptor-mediated uptakes and the specificity was higher in 5.5 nm SPIONs, due to its higher folic acid (FA) density, without inhibition. However, the numbers of the particles taken up under FA inhibition were similar, irrespective of their sizes.

  14. Alpha 1-adrenergic receptor-mediated phosphoinositide hydrolysis and prostaglandin E2 formation in Madin-Darby canine kidney cells. Possible parallel activation of phospholipase C and phospholipase A2

    International Nuclear Information System (INIS)

    Slivka, S.R.; Insel, P.A.

    1987-01-01

    alpha 1-Adrenergic receptors mediate two effects on phospholipid metabolism in Madin-Darby canine kidney (MDCK-D1) cells: hydrolysis of phosphoinositides and arachidonic acid release with generation of prostaglandin E2 (PGE2). The similarity in concentration dependence for the agonist (-)-epinephrine in eliciting these two responses implies that they are mediated by a single population of alpha 1-adrenergic receptors. However, we find that the kinetics of the two responses are quite different, PGE2 production occurring more rapidly and transiently than the hydrolysis of phosphoinositides. The antibiotic neomycin selectively decreases alpha 1-receptor-mediated phosphatidylinositol 4,5-bisphosphate hydrolysis without decreasing alpha 1-receptor-mediated arachidonic acid release and PGE2 generation. In addition, receptor-mediated inositol trisphosphate formation is independent of extracellular calcium, whereas release of labeled arachidonic acid is largely calcium-dependent. Moreover, based on studies obtained with labeled arachidonic acid, receptor-mediated generation of arachidonic acid cannot be accounted for by breakdown of phosphatidylinositol monophosphate, phosphatidylinositol bisphosphate, or phosphatidic acid. Further studies indicate that epinephrine produces changes in formation or turnover of several classes of membrane phospholipids in MDCK cells. We conclude that alpha 1-adrenergic receptors in MDCK cells appear to regulate phospholipid metabolism by the parallel activation of phospholipase C and phospholipase A2. This parallel activation of phospholipases contrasts with models described in other systems which imply sequential activation of phospholipase C and diacylglycerol lipase or phospholipase A2

  15. Radioiodine uptake in inactive pulmonary tuberculosis

    International Nuclear Information System (INIS)

    Bakheet, S.M.; Powe, J.; Al Suhaibani, H.; Hammami, M.M.; Bazarbashi, M.

    1999-01-01

    Radioiodine may accumulate at sites of inflammation or infection. We have seen such accumulation in six thyroid cancer patients with a history of previously treated pulmonary tuberculosis. We also review the causes of false-positive radioiodine uptake in lung infection/inflammation. Eight foci of radioiodine uptake were seen on six iodine-123 diagnostic scans. In three foci, the uptake was focal and indistinguishable from thyroid cancer pulmonary metastases from thyroid cancer. In the remaining foci, the uptake appeared nonsegmental, linear or lobar, suggesting a false-positive finding. The uptake was unchanged, variable in appearance or non-persistent on follow-up scans and less extensive than the fibrocystic changes seen on chest radiographs. In the two patients studied, thyroid hormone level did not affect the radioiodine lung uptake and there was congruent gallium-67 uptake. None of the patients had any evidence of thyroid cancer recurrence or of reactivation of tuberculosis and only two patients had chronic intermittent chest symptoms. Severe bronchiectasis, active tuberculosis, acute bronchitis, respiratory bronchiolitis, rheumatoid arthritis-associated lung disease and fungal infection such as Allescheria boydii and aspergillosis can lead to different patterns of radioiodine chest uptake mimicking pulmonary metastases. Pulmonary scarring secondary to tuberculosis may predispose to localized radioiodine accumulation even in the absence of clinically evident active infection. False-positive radioiodine uptake due to pulmonary infection/inflammation should be considered in thyroid cancer patients prior to the diagnosis of pulmonary metastases. (orig.)

  16. Bioidentical Hormones and Menopause

    Science.gov (United States)

    ... Endocrinologist Search Featured Resource Menopause Map™ View Bioidentical Hormones January 2012 Download PDFs English Espanol Editors Howard ... take HT for symptom relief. What are bioidentical hormones? Bioidentical hormones are identical to the hormones that ...

  17. Nitric oxide inhibits the bradykinin B2 receptor-mediated adrenomedullary catecholamine release but has no effect on adrenal blood flow response in vivo.

    Science.gov (United States)

    Bouallegue, Ali; Yamaguchi, Nobuharu

    2005-06-01

    The role of nitric oxide (NO) in bradykinin (BK)-induced adrenal catecholamine secretion still remains obscure. The present study was to investigate whether an inhibition of NO synthase with N(omega)-nitro-L-arginine methyl ester (L-NAME) would modulate BK-induced adrenal catecholamine secretion (ACS) and adrenal vasodilating response (AVR) in anesthetized dogs. Plasma catecholamine concentrations were determined with an HPLC coupled with an electrochemical detector. All drugs were locally administered to the left adrenal gland via intra-arterial infusion. BK dose-dependently increased both ACS and AVR. Hoe-140, a selective B(2) antagonist, significantly blocked the BK-induced increases in both ACS and AVR. In the presence of L-NAME, the BK-induced ACS was significantly enhanced, while the simultaneous AVR remained unaffected. These results suggest that the both BK-induced ACS and AVR are primarily mediated by B(2) receptors in the canine adrenal gland. Our results also suggest that the enhanced ACS in response to BK in the presence of L-NAME may have resulted from a specific inhibition of NO formation in the adrenal gland. It is concluded that the BK-induced NO may play an inhibitory role in the B(2)-receptor-mediated mechanisms regulating ACS, while it may not be implicated in the B(2)-receptor-mediated AVR under in vivo conditions.

  18. Ga-66 labeled somatostatin analogue DOTA-DPhe1-Tyr3-octreotide as a potential agent for positron emission tomography imaging and receptor mediated internal radiotherapy of somatostatin receptor positive tumors

    International Nuclear Information System (INIS)

    Ugur, Oemer; Kothari, Paresh J.; Finn, Ronald D.; Zanzonico, Pat; Ruan, Shutian; Guenther, Ilonka; Maecke, Helmut R.; Larson, Steven M.

    2002-01-01

    Radionuclide labeled somatostatin analogues selectively target somatostatin receptor (SSTR)-expressing tumors as a basis for diagnosis and treatment of these tumors. Recently, a DOTA-functionalized somatostatin analogue, DOTATOC (DOTA-DPhe 1 -Tyr 3 -octreotide) has been developed. This compound has been shown to be superior to the other somatostatin analogues as indicated by its uniquely high tumor-to-non-target tissue ratio. DOTATOC can be labeled with a variety of radiometals including gallium radioisotopes. Gallium-66 is a positron emitting radionuclide (T 1/2 =9.5 hr; β + =56%), that can be produced in carrier free form by a low-beam energy cyclotron. In this study we investigated SSTR targeting characteristics of 66 Ga-DOTATOC in AR42J rat pancreas tumor implanted nude mice as a potential agent for diagnosis and receptor-mediated internal radiotherapy of SSTR-expressing tumors. We compared our results with 67 Ga- and 68 Ga- labeled DOTATOC. The radiolabeling procedure gave labeling yield ranged from 85-95% and radiochemical and chemical purity was >95%. In-vitro competitive binding curves and in-vivo competitive displacement studies with an excess of unlabeled peptide indicates that there is specific binding of the radioligand to SSTR. Animal biodistribution data and serial microPET TM images demonstrated rapid tumor uptake and rapid clearance from the blood and all tissues except kidney. Maximum % ID/g values for tumor were 10.0±0.7, 13.2±2.1 and 9.8±1.5 for 66 Ga-, 67 Ga-, and 68 Ga-DOTATOC, respectively. Calculated tumor, kidney and bone marrow doses for 66 Ga-DOTATOC based on biodistribution data were 178, 109 and 1.2 cGy/MBq, respectively. We conclude that 66 Ga labeled DOTATOC can be used for PET diagnosis and quantitative imaging-based dosimetry of SSTR positive tumors. 66 Ga-DOTATOC may also be used in higher doses for ablation of these tumors. However, kidney is the critical organ for toxicity (tumor/kidney ratio 1.64), and high kidney uptake must

  19. Ga-66 labeled somatostatin analogue DOTA-DPhe{sup 1}-Tyr{sup 3}-octreotide as a potential agent for positron emission tomography imaging and receptor mediated internal radiotherapy of somatostatin receptor positive tumors

    Energy Technology Data Exchange (ETDEWEB)

    Ugur, Oemer E-mail: ougur@hacettepe.edu.tr; Kothari, Paresh J.; Finn, Ronald D.; Zanzonico, Pat; Ruan, Shutian; Guenther, Ilonka; Maecke, Helmut R.; Larson, Steven M

    2002-02-01

    Radionuclide labeled somatostatin analogues selectively target somatostatin receptor (SSTR)-expressing tumors as a basis for diagnosis and treatment of these tumors. Recently, a DOTA-functionalized somatostatin analogue, DOTATOC (DOTA-DPhe{sup 1}-Tyr{sup 3}-octreotide) has been developed. This compound has been shown to be superior to the other somatostatin analogues as indicated by its uniquely high tumor-to-non-target tissue ratio. DOTATOC can be labeled with a variety of radiometals including gallium radioisotopes. Gallium-66 is a positron emitting radionuclide (T{sub 1/2} =9.5 hr; {beta}{sup +}=56%), that can be produced in carrier free form by a low-beam energy cyclotron. In this study we investigated SSTR targeting characteristics of {sup 66}Ga-DOTATOC in AR42J rat pancreas tumor implanted nude mice as a potential agent for diagnosis and receptor-mediated internal radiotherapy of SSTR-expressing tumors. We compared our results with {sup 67}Ga- and {sup 68}Ga- labeled DOTATOC. The radiolabeling procedure gave labeling yield ranged from 85-95% and radiochemical and chemical purity was >95%. In-vitro competitive binding curves and in-vivo competitive displacement studies with an excess of unlabeled peptide indicates that there is specific binding of the radioligand to SSTR. Animal biodistribution data and serial microPET{sup TM} images demonstrated rapid tumor uptake and rapid clearance from the blood and all tissues except kidney. Maximum % ID/g values for tumor were 10.0{+-}0.7, 13.2{+-}2.1 and 9.8{+-}1.5 for {sup 66}Ga-, {sup 67}Ga-, and {sup 68}Ga-DOTATOC, respectively. Calculated tumor, kidney and bone marrow doses for {sup 66}Ga-DOTATOC based on biodistribution data were 178, 109 and 1.2 cGy/MBq, respectively. We conclude that {sup 66}Ga labeled DOTATOC can be used for PET diagnosis and quantitative imaging-based dosimetry of SSTR positive tumors. {sup 66}Ga-DOTATOC may also be used in higher doses for ablation of these tumors. However, kidney is the

  20. In vivo evaluation of radiotracers targeting the melanin-concentrating hormone receptor 1: [11C]SNAP-7941 and [18F]FE@SNAP reveal specific uptake in the ventricular system.

    Science.gov (United States)

    Zeilinger, Markus; Dumanic, Monika; Pichler, Florian; Budinsky, Lubos; Wadsak, Wolfgang; Pallitsch, Katharina; Spreitzer, Helmut; Lanzenberger, Rupert; Hacker, Marcus; Mitterhauser, Markus; Philippe, Cécile

    2017-08-14

    The MCHR1 is involved in the regulation of energy homeostasis and changes of the expression are linked to a variety of associated diseases, such as diabetes and adiposity. The study aimed at the in vitro and in vivo evaluation of [ 11 C]SNAP-7941 and [ 18 F]FE@SNAP as potential PET-tracers for the MCHR1. Competitive binding studies with non-radioactive derivatives and small-animal PET/CT and MRI brain studies were performed under baseline conditions and tracer displacement with the unlabelled MCHR1 antagonist (±)-SNAP-7941. Binding studies evinced high binding affinity of the non-radioactive derivatives. Small-animal imaging of [ 11 C]SNAP-7941 and [ 18 F]FE@SNAP evinced high tracer uptake in MCHR1-rich regions of the ventricular system. Quantitative analysis depicted a significant tracer reduction after displacement with (±)-SNAP-7941. Due to the high binding affinity of the non-labelled derivatives and the high specific tracer uptake of [ 11 C]SNAP-7941 and [ 18 F]FE@SNAP, there is strong evidence that both radiotracers may serve as highly suitable agents for specific MCHR1 imaging.

  1. A novel ecdysone receptor mediates steroid-regulated developmental events during the mid-third instar of Drosophila.

    Directory of Open Access Journals (Sweden)

    Benjamin F B Costantino

    2008-06-01

    Full Text Available The larval salivary gland of Drosophila melanogaster synthesizes and secretes glue glycoproteins that cement developing animals to a solid surface during metamorphosis. The steroid hormone 20-hydroxyecdysone (20E is an essential signaling molecule that modulates most of the physiological functions of the larval gland. At the end of larval development, it is known that 20E--signaling through a nuclear receptor heterodimer consisting of EcR and USP--induces the early and late puffing cascade of the polytene chromosomes and causes the exocytosis of stored glue granules into the lumen of the gland. It has also been reported that an earlier pulse of hormone induces the temporally and spatially specific transcriptional activation of the glue genes; however, the receptor responsible for triggering this response has not been characterized. Here we show that the coordinated expression of the glue genes midway through the third instar is mediated by 20E acting to induce genes of the Broad Complex (BRC through a receptor that is not an EcR/USP heterodimer. This result is novel because it demonstrates for the first time that at least some 20E-mediated, mid-larval, developmental responses are controlled by an uncharacterized receptor that does not contain an RXR-like component.

  2. Investigation of the receptor-mediated endocytosis of transcobalamin/intrinsic factor-vitamin B12 complexes

    DEFF Research Database (Denmark)

    Beedholm, Rasmus; Grissom, Charles B.; Fedosov, Sergey N.

    receptor structure. This receptor is suggested to be regulated by the vitamin B12 level in the cells, which is interesting in relation to cancer growth. The cellular endocytosis of TC- B12 complex by this unknown receptor is being investigated, using confocal microscopy. Fluorescently labeled B12 molecules...... (Oregon green linked to B12) have been synthesized to determine the B12 uptake level in normal and various tumour-derived cells (e.g. Hela cells from cervix epithelioid carcinoma and BN- cells from rat yolk sac sarcoma). Costaining of the B12 binders has been performed using fluorescently labelled...

  3. Hormones in international meat production: biological, sociological and consumer issues.

    Science.gov (United States)

    Galbraith, Hugh

    2002-12-01

    Beef and its products are an important source of nutrition in many human societies. Methods of production vary and include the use of hormonal compounds ('hormones') to increase growth and lean tissue with reduced fat deposition in cattle. The hormonal compounds are naturally occurring in animals or are synthetically produced xenobiotics and have oestrogenic (oestradiol-17beta and its esters; zeranol), androgenic (testosterone and esters; trenbolone acetate) or progestogenic (progesterone; melengestrol acetate) activity. The use of hormones as production aids is permitted in North American countries but is no longer allowed in the European Union (EU), which also prohibits the importation of beef and its products derived from hormone-treated cattle. These actions have resulted in a trade dispute between the two trading blocs. The major concern for EU authorities is the possibility of adverse effects on human consumers of residues of hormones and metabolites. Methods used to assess possible adverse effects are typical of those used by international agencies to assess acceptability of chemicals in human food. These include analysis of quantities present in the context of known biological activity and digestive, absorptive, post-absorptive and excretory processes. Particular considerations include the low quantities of hormonal compounds consumed in meat products and their relationships to endogenous production particularly in prepubertal children, enterohepatic inactivation, cellular receptor- and non-receptor-mediated effects and potential for interference with growth, development and physiological function in consumers. There is particular concern about the role of oestradiol-17beta as a carcinogen in certain tissues. Now subject to a 'permanent' EU ban, current evidence suggests that certain catechol metabolites may induce free-radical damage of DNA in cell and laboratory animal test systems. Classical oestrogen-receptor mediation is considered to stimulate

  4. Synthesis of 99mTc-oxybutynin for M3-receptor-mediated imaging of urinary bladder

    International Nuclear Information System (INIS)

    Moustapha, M.E.; Benha University, Benha; Motaleb, M.A.; Ibrahim, I.T.

    2011-01-01

    Radiolabeling of oxybutynin, a muscarinic acetylcholine (mACh) receptor antagonist agent with 99m Tc is of considerable interest for imaging of urinary bladder. This study is aimed to optimize radiolabeling yield of oxybutynin with 99m Tc using SnCl 2 x 2H 2 O as a reducing agent with respect to factors that affect the reaction conditions such as oxybutynin amount, stannous chloride amount, reaction time and pH of the reaction mixture. In vitro stability of the radiolabeled complex was checked and it was found to be stable for up to 8 h. 99m Tc-oxybutynin was injected via subcutaneous and intravenous administration routes into normal Sprague-Dawley rats. Biodistribution studies have revealed that 99m Tc-oxybutynin exhibits high affinity and specificity for the muscarinic M 3 subtype located on the smooth muscle of urinary bladder relative to the M 1 and M 2 subtypes of the G protein coupled receptor (GPCR) superfamily. In vivo uptake of subcutaneous 99m Tc-oxybutynin in urinary bladder was 19.6 ± 0.42% ID at 0.5 h, whereas in intravenous administration route the accumulation in the urinary bladder was found to be 9.4 ± 0.31% ID at 0.5 h post injection. Administration of cold oxybutynin effectively blocked urinary bladder uptake and further confirms the high specificity of this complex for the M 3 receptor. (author)

  5. Permanent Distal Occlusion of Middle Cerebral Artery in Rat Causes Local Increased ETB, 5-HT1B and AT1 Receptor-Mediated Contractility Downstream of Occlusion

    DEFF Research Database (Denmark)

    Rasmussen, Marianne N P; Hornbak, Malene; Larsen, Stine S

    2013-01-01

    Background/Aims: In response to experimental stroke, a characteristic functional and expressional upregulation of contractile G-protein-coupled receptors has been uncovered in the affected cerebral vasculature; however, the mechanism initiating this phenomenon remains unknown. Methods: Using...... a model of permanent distal occlusion of rat middle cerebral arteries, we investigated whether there was a regional difference in receptor-mediated contractility of segments located upstream and downstream of the occlusion site. The contractile response to endothelin, angiotensin and 5-hydroxytryptamine...... receptor stimulation was studied by sensitive wire myograph. Results: Only downstream segments exhibited an augmented contractile response to stimulation with each of the three ligands, with the response towards sarafotoxin 6c being especially augmented compared to sham, upstream and contralateral controls...

  6. A comprehensive curated resource for follicle stimulating hormone signaling

    Directory of Open Access Journals (Sweden)

    Sharma Jyoti

    2011-10-01

    Full Text Available Abstract Background Follicle stimulating hormone (FSH is an important hormone responsible for growth, maturation and function of the human reproductive system. FSH regulates the synthesis of steroid hormones such as estrogen and progesterone, proliferation and maturation of follicles in the ovary and spermatogenesis in the testes. FSH is a glycoprotein heterodimer that binds and acts through the FSH receptor, a G-protein coupled receptor. Although online pathway repositories provide information about G-protein coupled receptor mediated signal transduction, the signaling events initiated specifically by FSH are not cataloged in any public database in a detailed fashion. Findings We performed comprehensive curation of the published literature to identify the components of FSH signaling pathway and the molecular interactions that occur upon FSH receptor activation. Our effort yielded 64 reactions comprising 35 enzyme-substrate reactions, 11 molecular association events, 11 activation events and 7 protein translocation events that occur in response to FSH receptor activation. We also cataloged 265 genes, which were differentially expressed upon FSH stimulation in normal human reproductive tissues. Conclusions We anticipate that the information provided in this resource will provide better insights into the physiological role of FSH in reproductive biology, its signaling mediators and aid in further research in this area. The curated FSH pathway data is freely available through NetPath (http://www.netpath.org, a pathway resource developed previously by our group.

  7. Uptake of benzyladenine by excised watermelon cotyledons.

    Science.gov (United States)

    Lampugnani, M G; Fantelli, R; Longo, G P; Longo, C P; Rossi, G

    1981-07-01

    The uptake of 8-[(14)C]N(6)-benzyladenine (BA) was studied in excised watermelon (Citrullus vulgaris Schrad.) cotyledons 24 hours after the start of imbibition. The passive nature of this uptake is suggested by the following evidence: (a) no sign of saturation on increasing external concentration of BA; (b) no decrease in uptake under conditions that inhibit ATP synthesis; (c) no change in amount of radioactivity absorbed when cotyledons are frozen and thawed before the uptake test. About two-thirds of the radioactivity taken up is released after 12 hours of washing. If the washing is performed at 2 C very little radioactivity is released.There seems to be a correlation between the level of radioactivity (i.e. of BA + derivatives) present in the cotyledons and the magnitude of hormonal responses that are observed four days after uptake. This relationship holds regardless of whether a given level of radioactivity has been reached after a short period of uptake or after a long period of uptake followed by washing.

  8. Glutamate AMPA/kainate receptors, not GABA(A) receptors, mediate estradiol-induced sex differences in the hypothalamus.

    Science.gov (United States)

    Todd, Brigitte J; Schwarz, Jaclyn M; Mong, Jessica A; McCarthy, Margaret M

    2007-02-15

    Sex differences in brain morphology underlie physiological and behavioral differences between males and females. During the critical perinatal period for sexual differentiation in the rat, gonadal steroids act in a regionally specific manner to alter neuronal morphology. Using Golgi-Cox impregnation, we examined several parameters of neuronal morphology in postnatal day 2 (PN2) rats. We found that in the ventromedial nucleus of the hypothalamus (VMN) and in areas just dorsal and just lateral to the VMN that there was a sex difference in total dendritic spine number (males greater) that was abolished by treating female neonates with exogenous testosterone. Dendritic branching was similarly sexually differentiated and hormonally modulated in the VMN and dorsal to the VMN. We then used spinophilin, a protein that positively correlates with the amount of dendritic spines, to investigate the mechanisms underlying these sex differences. Estradiol, which mediates most aspects of masculinization and is the aromatized product of testosterone, increased spinophilin levels in female PN2 rats to that of males. Muscimol, an agonist at GABA(A) receptors, did not affect spinophilin protein levels in either male or female neonates. Kainic acid, an agonist at glutamatergic AMPA/kainate receptors, mimicked the effect of estradiol in females. Antagonizing AMPA/kainate receptors with NBQX prevented the estradiol-induced increase in spinophilin in females but did not affect spinophilin level in males. (c) 2007 Wiley Periodicals, Inc.

  9. AIB1 is required for the acquisition of epithelial growth factor receptor-mediated tamoxifen resistance in breast cancer cells

    International Nuclear Information System (INIS)

    Zhao Wenhui; Zhang Qingyuan; Kang Xinmei; Jin Shi; Lou Changjie

    2009-01-01

    Acquired resistance to tamoxifen has become a serious obstacle in breast cancer treatment. The underlying mechanism responsible for this condition has not been completely elucidated. In this study, a tamoxifen-resistant (Tam-R) MCF-7 breast cancer cell line was developed to mimic the occurrence of acquired tamoxifen resistance as seen in clinical practice. Increased expression levels of HER1, HER2 and the estrogen receptor (ER)-AIB1 complex were found in tamoxifen-resistant cells. EGF stimulation and gefitinib inhibition experiments further demonstrated that HER1/HER2 signaling and AIB1 were involved in the proliferation of cells that had acquired Tam resistance. However, when AIB1 was silenced with AIB1-siRNA in Tam-R cells, the cell growth stimulated by the HER1/HER2 signaling pathway was significantly reduced, and the cells were again found to be inhibited by tamoxifen. These results suggest that the AIB1 protein could be a limiting factor in the HER1/HER2-mediated hormone-independent growth of Tam-R cells. Thus, AIB1 may be a new therapeutic target, and the removal of AIB1 may decrease the crosstalk between ER and the HER1/HER2 pathway, resulting in the restoration of tamoxifen sensitivity in tamoxifen-resistant cells.

  10. Timing is critical for effective glucocorticoid receptor mediated repression of the cAMP-induced CRH gene.

    Directory of Open Access Journals (Sweden)

    Siem van der Laan

    Full Text Available Glucocorticoid negative feedback of the hypothalamus-pituitary-adrenal axis is mediated in part by direct repression of gene transcription in glucocorticoid receptor (GR expressing cells. We have investigated the cross talk between the two main signaling pathways involved in activation and repression of corticotrophin releasing hormone (CRH mRNA expression: cyclic AMP (cAMP and GR. We report that in the At-T20 cell-line the glucocorticoid-mediated repression of the cAMP-induced human CRH proximal promoter activity depends on the relative timing of activation of both signaling pathways. Activation of the GR prior to or in conjunction with cAMP signaling results in an effective repression of the cAMP-induced transcription of the CRH gene. In contrast, activation of the GR 10 minutes after onset of cAMP treatment, results in a significant loss of GR-mediated repression. In addition, translocation of ligand-activated GR to the nucleus was found as early as 10 minutes after glucocorticoid treatment. Interestingly, while both signaling cascades counteract each other on the CRH proximal promoter, they synergize on a synthetic promoter containing 'positive' response elements. Since the order of activation of both signaling pathways may vary considerably in vivo, we conclude that a critical time-window exists for effective repression of the CRH gene by glucocorticoids.

  11. Role of the metabolism of parathyroid hormone

    International Nuclear Information System (INIS)

    Teitelbaum, A.P.

    1978-01-01

    The heterogeneity of parathyroid hormone (PTH) in plasma has prompted investigations of the metabolism of PTH and its relationship to hormone action. The time course of tissue distribution and metabolism of electrolytically iodinated PTH (E-PTH) previously shown to retain biological activity was compared with that of inactive PTH iodinated with Chloramine-T (CT-PTH). Labeled PTH (0.4 μg) was injected in the saphenous veins of anesthetized rats which were sacrificed at 1, 3, 5, 10, and 20 min. Tissue extracts from kidney, liver, and serum were chromatographed to separate intact PTH from its metabolites. In the kidney, the initial rate of degradation of E-PTH was greater than that of CT-PTH. The difference in initial rates of metabolism may be due, in part, to receptor-specific hydrolysis on peritubular cell membranes which selectively act on biologically active PTH molecules. PTH-responsive adenyl cyclase activity in isolated kidney cortex plasma membranes was measured and PTH metabolism was monitored simultaneously. When degradation was completely blocked by histone f 3 (1 mg/ml), adenyl cyclase activity was significantly increased over control. In addition, when adenyl cyclase activity was negligible, the rate of PTH degradation by the membranes was not significantly diminished. Consistent with the in vivo data was the observation that E-PTH is metabolized by these membranes at a greater rate than CT-PTH. The data demonstrate the existence of a receptor-specific metabolism at sites which are independent of PTH receptor mediated adenyl cyclase activity

  12. Entry of porcine reproductive and respiratory syndrome virus into porcine alveolar macrophages via receptor-mediated endocytosis.

    Science.gov (United States)

    Nauwynck, H J; Duan, X; Favoreel, H W; Van Oostveldt, P; Pensaert, M B

    1999-02-01

    Porcine alveolar macrophages (AMphi) are the dominant cell type that supports the replication of porcine reproductive and respiratory syndrome virus (PRRSV) in vivo and in vitro. In order to determine the characteristics of the virus-receptor interaction, the attachment of PRRSV to cells was examined by using biotinylated virus in a series of flow cytometric assays. PRRSV bound specifically to AMphi in a dose-dependent manner. Binding of PRRSV to AMphi increased gradually and reached a maximum within 60 min at 4 degrees C. By confocal microscopy, it was shown that different degrees of PRRSV binding exist and that entry is by endocytosis. Virus uptake in vesicles is a clathrin-dependent process, as it was blocked by the addition of cytochalasin D and co-localization of PRRSV and clathrin was found. Furthermore, by the use of two weak bases, NH4Cl and chloroquine, it was demonstrated that PRRSV uses a low pH-dependent entry pathway. In the presence of these reagents, input virions accumulated in large vacuoles, indicating that uncoating was prevented. These results indicate that PRRSV entry into AMphi involves attachment to a specific virus receptor(s) followed by a process of endocytosis, by which virions are taken into the cell within vesicles by a clathrin-dependent pathway. A subsequent drop in pH is required for proper virus replication.

  13. A membrane glucocorticoid receptor mediates the rapid/non-genomic actions of glucocorticoids in mammalian skeletal muscle fibres.

    Science.gov (United States)

    Pérez, María Hernández-Alcalá; Cormack, Jonathan; Mallinson, David; Mutungi, Gabriel

    2013-10-15

    Glucocorticoids (GCs) are steroid hormones released from the adrenal gland in response to stress. They are also some of the most potent anti-inflammatory and immunosuppressive drugs currently in clinical use. They exert most of their physiological and pharmacological actions through the classical/genomic pathway. However, they also have rapid/non-genomic actions whose physiological and pharmacological functions are still poorly understood. Therefore, the primary aim of this study was to investigate the rapid/non-genomic effects of two widely prescribed glucocorticoids, beclomethasone dipropionate (BDP) and prednisolone acetate (PDNA), on force production in isolated, intact, mouse skeletal muscle fibre bundles. The results show that the effects of both GCs on maximum isometric force (Po) were fibre-type dependent. Thus, they increased Po in the slow-twitch fibre bundles without significantly affecting that of the fast-twitch fibre bundles. The increase in Po occurred within 10 min and was insensitive to the transcriptional inhibitor actinomycin D. Also, it was maximal at ∼250 nM and was blocked by the glucocorticoid receptor (GCR) inhibitor RU486 and a monoclonal anti-GCR, suggesting that it was mediated by a membrane (m) GCR. Both muscle fibre types expressed a cytosolic GCR. However, a mGCR was present only in the slow-twitch fibres. The receptor was more abundant in oxidative than in glycolytic fibres and was confined mainly to the periphery of the fibres where it co-localised with laminin. From these findings we conclude that the rapid/non-genomic actions of GCs are mediated by a mGCR and that they are physiologically/therapeutically beneficial, especially in slow-twitch muscle fibres.

  14. Guanine nucleotide regulation of muscarinic receptor-mediated inositol phosphate formation in permeabilized 1321N1 cells

    International Nuclear Information System (INIS)

    Orellana, S.A.; Trilivas, I.; Brown, J.H.

    1986-01-01

    Carbachol and guanine nucleotides stimulate formation of the ( 3 H)inositol phosphates IP, IP2, and IP3 in saponin-permeabilized monolayers labelled with ( 3 H) inositol. Carbachol alone has little effect on formation of the ( 3 H) inositol phosphates (IPs), but GTPγS causes synergistic accumulation of ( 3 H)IPs to levels similar to those seen in intact cells. GTP, GppNHp, and GTPγS all support formation of the ( 3 H)IPs, with or without hormone, but GTPγS is the most effective. In the presence of GTPγS, the effect of carbachol is dose-dependent. Half-maximal and maximal accumulation of the ( 3 H)IPs occur at ∼ 5 μM and ∼ 100 μM carbachol, respectively; values close to those seen in intact cells. GTPγS alone stimulates formation of the ( 3 H)IPs after a brief lag time. The combination of GTPγS and carbachol both increases the rate of, and decreases the lag in, formation of the ( 3 H)IPs. LiCl increases ( 3 H)IP and IP2, but not IP3, accumulation; while 2,3-diphosphoglycerate substantially increases that of ( 3 H)IP3. GTPγS and carbachol cause formation of ( 3 H)IPs in the absence of Ca ++ , but formation induced by GTPγS with or without carbachol is Ca ++ -sensitive over a range of physiological concentrations. Although carbachol, Ca ++ , and GTPγS all have effects on formation of ( 3 H)IPs, GTPγS appears to be a primary and obligatory regulator of phosphoinositide hydrolysis in the permeabilized 1321N1 astrocytoma cell

  15. Glucocorticoid receptor, but not mineralocorticoid receptor, mediates cortisol regulation of epidermal ionocyte development and ion transport in zebrafish (danio rerio.

    Directory of Open Access Journals (Sweden)

    Shelly Abad Cruz

    Full Text Available Cortisol is the major endogenous glucocorticoid (GC both in human and fish, mediated by corticosteroid receptors. Due to the absence of aldosterone production in teleost fish, cortisol is also traditionally accepted to function as mineralocorticoid (MC; but whether it acts through the glucocorticoid receptor (GR or the mineralocorticoid receptor (MR remains a subject of debate. Here, we used loss-of-function and rescue assays to determine whether cortisol affects zebrafish epidermal ionocyte development and function via the GR and/or the MR. GR knockdown morphants displayed a significant decrease in the major ionocytes, namely Na(+-K(+-ATPase-rich cells (NaRCs and H(+-ATPase-rich cells (HRCs, as well as other cells, including epidermal stem cells (ESCs, keratinocytes, and mucus cells; conversely, cell numbers were unaffected in MR knockdown morphants. In agreement, GR morphants, but not MR morphants, exhibited decreased NaRC-mediated Ca(2+ uptake and HRC-mediated H(+ secretion. Rescue via GR capped mRNA injection or exogenous cortisol incubation normalized the number of epidermal ionocytes in GR morphants. We also provide evidence for GR localization in epidermal cells. At the transcript level, GR mRNA is ubiquitously expressed in gill sections and present in both NaRCs and HRCs, supporting the knockdown and functional assay results in embryo. Altogether, we have provided solid molecular evidence that GR is indeed present on ionocytes, where it mediates the effects of cortisol on ionocyte development and function. Hence, cortisol-GR axis performs the roles of both GC and MC in zebrafish skin and gills.

  16. Depression of NMDA receptor-mediated synaptic transmission by four α2 adrenoceptor agonists on the in vitro rat spinal cord preparation

    Science.gov (United States)

    Faber, E S L; Chambers, J P; Evans, R H

    1998-01-01

    α2-Adrenoceptor agonists have a spinal site of analgesic action. In the current study the synaptic depressant actions of xylazine, detomidine, romifidine and dexmedetomidine have been compared on segmental reflexes containing NMDA receptor-mediated components in the neonatal rat hemisected spinal cord preparation in vitro.Reflexes were evoked in the ventral root following either supramaximal electrical stimulation of the corresponding ipsilateral lumbar dorsal root to evoke the high intensity excitatory postsynaptic potential (e.p.s.p.) involving all primary afferent fibres, or low intensity stimulation to evoke the solely A fibre-mediated low intensity e.p.s.p. The high intensity e.p.s.p. contains a greater NMDA receptor-mediated component.Xylazine, romifidine, detomidine and dexmedetomidine all depressed both the high intensity e.p.s.p. and the low intensity e.p.s.p. giving respective EC50 values of 0.91±0.2 μM (n=12), 23.4±3 nM (n=12), 37.7±7 nM (n=8) and 0.84±0.1 nM (n=4) for depression of the high intensity e.p.s.p. and 0.76±0.1 μM (n=12), 22.0±3 nM (n=12), 24.9±6 nM (n=4) and 2.7±0.6 nM (n=4) for depression of the low intensity e.p.s.p., respectively. Unlike the other three drugs, the two values for dexmedetomidine, showing a greater selectivity for the high intensity e.p.s.p., are significantly different.Each of these depressant actions was reversed by the selective α2-adrenoceptor antagonist atipamezole (1 μM).In contrast to previous reports of the actions of α2-adrenoceptor agonists on the in vitro spinal cord preparation, at concentrations ten fold higher than the above EC50 values xylazine, romifidine, detomidine and dexmedetomidine depressed the initial population spike of motoneurons (MSR). This depression was not reversed by atipamezole.Comparison of the rank order of the present EC50 values for depression of the high intensity e.p.s.p. with potency ratios from in vivo analgesic tests in previous studies show a close

  17. Hormones and absence epilepsy

    NARCIS (Netherlands)

    Luijtelaar, E.L.J.M. van; Tolmacheva, E.A.; Budziszewska, B.; Stein, J.

    2017-01-01

    Hormones have an extremely large impact on seizures and epilepsy. Stress and stress hormones are known to reinforce seizure expression, and gonadal hormones affect the number of seizures and even the seizure type. Moreover, hormonal concentrations change drastically over an individual's lifetime,

  18. GABA(A receptor-mediated acceleration of aging-associated memory decline in APP/PS1 mice and its pharmacological treatment by picrotoxin.

    Directory of Open Access Journals (Sweden)

    Yuji Yoshiike

    Full Text Available Advanced age and mutations in the genes encoding amyloid precursor protein (APP and presenilin (PS1 are two serious risk factors for Alzheimer's disease (AD. Finding common pathogenic changes originating from these risks may lead to a new therapeutic strategy. We observed a decline in memory performance and reduction in hippocampal long-term potentiation (LTP in both mature adult (9-15 months transgenic APP/PS1 mice and old (19-25 months non-transgenic (nonTg mice. By contrast, in the presence of bicuculline, a GABA(A receptor antagonist, LTP in adult APP/PS1 mice and old nonTg mice was larger than that in adult nonTg mice. The increased LTP levels in bicuculline-treated slices suggested that GABA(A receptor-mediated inhibition in adult APP/PS1 and old nonTg mice was upregulated. Assuming that enhanced inhibition of LTP mediates memory decline in APP/PS1 mice, we rescued memory deficits in adult APP/PS1 mice by treating them with another GABA(A receptor antagonist, picrotoxin (PTX, at a non-epileptic dose for 10 days. Among the saline vehicle-treated groups, substantially higher levels of synaptic proteins such as GABA(A receptor alpha1 subunit, PSD95, and NR2B were observed in APP/PS1 mice than in nonTg control mice. This difference was insignificant among PTX-treated groups, suggesting that memory decline in APP/PS1 mice may result from changes in synaptic protein levels through homeostatic mechanisms. Several independent studies reported previously in aged rodents both an increased level of GABA(A receptor alpha1 subunit and improvement of cognitive functions by long term GABA(A receptor antagonist treatment. Therefore, reduced LTP linked to enhanced GABA(A receptor-mediated inhibition may be triggered by aging and may be accelerated by familial AD-linked gene products like Abeta and mutant PS1, leading to cognitive decline that is pharmacologically treatable at least at this stage of disease progression in mice.

  19. Thyroid Scan and Uptake

    Medline Plus

    Full Text Available ... for a thyroid scan is 30 minutes or less. Thyroid Uptake You will be given radioactive iodine ( ... for each thyroid uptake is five minutes or less. top of page What will I experience during ...

  20. Thyroid Scan and Uptake

    Medline Plus

    Full Text Available ... uptake measurements are obtained at different times. For example, you may have uptake measurements at four to ... medicine procedures can be time consuming. It can take several hours to days for the radiotracer to ...

  1. Thyroid Scan and Uptake

    Medline Plus

    Full Text Available ... Scan and Uptake Thyroid scan and uptake uses small amounts of radioactive materials called radiotracers, a special ... is a branch of medical imaging that uses small amounts of radioactive material to diagnose and determine ...

  2. Thyroid Scan and Uptake

    Medline Plus

    Full Text Available ... radioactive iodine uptake test (RAIU) is also known as a thyroid uptake. It is a measurement of ... potential to identify disease in its earliest stages as well as a patient’s immediate response to therapeutic ...

  3. Thyroid Scan and Uptake

    Medline Plus

    Full Text Available ... known as a thyroid uptake. It is a measurement of thyroid function, but does not involve imaging. ... eating can affect the accuracy of the uptake measurement. Jewelry and other metallic accessories should be left ...

  4. Thyroid Scan and Uptake

    Medline Plus

    Full Text Available ... Uptake? A thyroid scan is a type of nuclear medicine imaging. The radioactive iodine uptake test (RAIU) ... of thyroid function, but does not involve imaging. Nuclear medicine is a branch of medical imaging that ...

  5. Thyroid Scan and Uptake

    Medline Plus

    Full Text Available ... for a thyroid scan is 30 minutes or less. Thyroid Uptake You will be given radioactive iodine (I-123 or I-131) in liquid or capsule form to swallow. The thyroid uptake will begin several hours to 24 hours later. Often, two separate uptake ...

  6. Cellular uptake of fluorophore-labeled glyco-DNA–gold nanoparticles

    International Nuclear Information System (INIS)

    Witten, Katrin G.; Ruff, Julie; Mohr, Anne; Görtz, Dieter; Recker, Tobias; Rinis, Natalie; Rech, Claudia; Elling, Lothar; Müller-Newen, Gerhard; Simon, Ulrich

    2013-01-01

    DNA-functionalized gold nanoparticles (AuNP–DNA) were hybridized with complementary di-N-acetyllactosamine-(di-LacNAc, [3Gal(β1-4)GlcNAc(β1-]2)-modified oligonucleotides to form glycol-functionalized particles, AuNP–DNA–di-LacNAc. While AuNP–DNA are known to be taken up by cells via scavenger receptors, glycol-functionalized particles have shown to be taken up via asialoglycoprotein receptors (ASGP-R). In this work, the interaction of these new particles with HepG2 cells was analyzed, which express scavenger receptors class B type I (SR-BI) and ASGP-R. To study the contribution of these receptors as potential mediators for cellular uptake, receptor-blocking experiments were performed with d-lactose, a ligand for ASGP-R, Fucoidan, a putative ligand for SR-BI, and a SR-BI blocking antibody. Labeling with Cy5-modified DNA ligands enabled us to monitor the particle uptake by confocal fluorescence microscopy and flow cytometry, in order to discriminate the two putative pathways by competitive binding studies. While SR-BI-antibody and d-lactose had no inhibiting effects on particle uptake Fucoidan led to a complete inhibition. Thus, a receptor-mediated uptake by the two receptors studied could not be proven and therefore other uptake mechanisms have to be considered

  7. Cellular uptake of fluorophore-labeled glyco-DNA-gold nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Witten, Katrin G.; Ruff, Julie [RWTH Aachen University, Institute of Inorganic Chemistry and JARA - Fundamentals of Future Information Technology (Germany); Mohr, Anne; Goertz, Dieter; Recker, Tobias; Rinis, Natalie [RWTH Aachen University, Institute of Biochemistry and Molecular Biology, University Hospital Aachen (Germany); Rech, Claudia; Elling, Lothar [RWTH Aachen University, Laboratory for Biomaterials, Institute of Biotechnology and Helmholtz-Institute for Biomedical Engineering (Germany); Mueller-Newen, Gerhard [RWTH Aachen University, Institute of Biochemistry and Molecular Biology, University Hospital Aachen (Germany); Simon, Ulrich, E-mail: ulrich.simon@ac.rwth-aachen.de [RWTH Aachen University, Institute of Inorganic Chemistry and JARA - Fundamentals of Future Information Technology (Germany)

    2013-10-15

    DNA-functionalized gold nanoparticles (AuNP-DNA) were hybridized with complementary di-N-acetyllactosamine-(di-LacNAc, [3Gal({beta}1-4)GlcNAc({beta}1-]2)-modified oligonucleotides to form glycol-functionalized particles, AuNP-DNA-di-LacNAc. While AuNP-DNA are known to be taken up by cells via scavenger receptors, glycol-functionalized particles have shown to be taken up via asialoglycoprotein receptors (ASGP-R). In this work, the interaction of these new particles with HepG2 cells was analyzed, which express scavenger receptors class B type I (SR-BI) and ASGP-R. To study the contribution of these receptors as potential mediators for cellular uptake, receptor-blocking experiments were performed with d-lactose, a ligand for ASGP-R, Fucoidan, a putative ligand for SR-BI, and a SR-BI blocking antibody. Labeling with Cy5-modified DNA ligands enabled us to monitor the particle uptake by confocal fluorescence microscopy and flow cytometry, in order to discriminate the two putative pathways by competitive binding studies. While SR-BI-antibody and d-lactose had no inhibiting effects on particle uptake Fucoidan led to a complete inhibition. Thus, a receptor-mediated uptake by the two receptors studied could not be proven and therefore other uptake mechanisms have to be considered.

  8. Autonomic control of body temperature and blood pressure: influences of female sex hormones.

    Science.gov (United States)

    Charkoudian, Nisha; Hart, Emma C J; Barnes, Jill N; Joyner, Michael J

    2017-06-01

    Female reproductive hormones exert important non-reproductive influences on autonomic regulation of body temperature and blood pressure. Estradiol and progesterone influence thermoregulation both centrally and peripherally, where estradiol tends to promote heat dissipation, and progesterone tends to promote heat conservation and higher body temperatures. Changes in thermoregulation over the course of the menstrual cycle and with hot flashes at menopause are mediated by hormonal influences on neural control of skin blood flow and sweating. The influence of estradiol is to promote vasodilation, which, in the skin, results in greater heat dissipation. In the context of blood pressure regulation, both central and peripheral hormonal influences are important as well. Peripherally, the vasodilator influence of estradiol contributes to the lower blood pressures and smaller risk of hypertension seen in young women compared to young men. This is in part due to a mechanism by which estradiol augments beta-adrenergic receptor mediated vasodilation, offsetting alpha-adrenergic vasoconstriction, and resulting in a weak relationship between muscle sympathetic nerve activity and total peripheral resistance, and between muscle sympathetic nerve activity and blood pressure. After menopause, with the loss of reproductive hormones, sympathetic nerve activity, peripheral resistance and blood pressure become more strongly related, and sympathetic nerve activity (which increases with age) becomes a more important contributor to the prevailing level of blood pressure. Continuing to increase our understanding of sex hormone influences on body temperature and blood pressure regulation will provide important insight for optimization of individualized health care for future generations of women.

  9. Escitalopram attenuates β-amyloid-induced tau hyperphosphorylation in primary hippocampal neurons through the 5-HT1A receptor mediated Akt/GSK-3β pathway.

    Science.gov (United States)

    Wang, Yan-Juan; Ren, Qing-Guo; Gong, Wei-Gang; Wu, Di; Tang, Xiang; Li, Xiao-Li; Wu, Fang-Fang; Bai, Feng; Xu, Lin; Zhang, Zhi-Jun

    2016-03-22

    Tau hyperphosphorylation is an important pathological feature of Alzheimer's disease (AD). To investigate whether escitalopram could inhibit amyloid-β (Aβ)-induced tau hyperphosphorylation and the underlying mechanisms, we treated the rat primary hippocampal neurons with Aβ1-42 and examined the effect of escitalopram on tau hyperphosphorylation. Results showed that escitalopram decreased Aβ1-42-induced tau hyperphosphorylation. In addition, escitalopram activated the Akt/GSK-3β pathway, and the PI3K inhibitor LY294002 blocked the attenuation of tau hyperphosphorylation induced by escitalopram. Moreover, the 5-HT1A receptor agonist 8-OH-DPAT also activated the Akt/GSK-3β pathway and decreased Aβ1-42-induced tau hyperphosphorylation. Furthermore, the 5-HT1A receptor antagonist WAY-100635 blocked the activation of Akt/GSK-3β pathway and the attenuation of tau hyperphosphorylation induced by escitalopram. Finally, escitalopram improved Aβ1-42 induced impairment of neurite outgrowth and spine density, and reversed Aβ1-42 induced reduction of synaptic proteins. Our results demonstrated that escitalopram attenuated Aβ1-42-induced tau hyperphosphorylation in primary hippocampal neurons through the 5-HT1A receptor mediated Akt/GSK-3β pathway.

  10. Chronic restraint stress causes a delayed increase in responding for palatable food cues during forced abstinence via a dopamine D1-like receptor-mediated mechanism.

    Science.gov (United States)

    Ball, Kevin T; Best, Olivia; Luo, Jonathan; Miller, Leah R

    2017-02-15

    Relapse to unhealthy eating habits in dieters is often triggered by stress. Animal models, moreover, have confirmed a causal role for acute stress in relapse. The role of chronic stress in relapse vulnerability, however, has received relatively little attention. Therefore, in the present study, we used an abstinence-based relapse model in rats to test the hypothesis that exposure to chronic stress increases subsequent relapse vulnerability. Rats were trained to press a lever for highly palatable food reinforcers in daily 3-h sessions and then tested for food seeking (i.e., responding for food associated cues) both before and after an acute or chronic restraint stress procedure (3h/day×1day or 10days, respectively) or control procedure (unstressed). The second food seeking test was conducted either 1day or 7days after the last restraint. Because chronic stress causes dopamine D1-like receptor-mediated alterations in prefrontal cortex (a relapse node), we also assessed dopaminergic involvement by administering either SCH-23390 (10.0μg/kg; i.p.), a dopamine D1-like receptor antagonist, or vehicle prior to daily treatments. Results showed that chronically, but not acutely, stressed rats displayed increased food seeking 7days, but not 1day, after the last restraint. Importantly, SCH-23390 combined with chronic stress reversed this effect. These results suggest that drugs targeting D 1 -like receptors during chronic stress may help to prevent future relapse in dieters. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Role of a guanine nucleotide-binding protein in α1-adrenergic receptor-mediated Ca2+ mobilization in DDT1 MF-2 cells

    International Nuclear Information System (INIS)

    Cornett, L.E.; Norris, J.S.

    1987-01-01

    In this study the mechanisms involved in α 1 -adrenergic receptor-mediated Ca 2+ mobilization at the level of the plasma membrane were investigated. Stimulation of 45 Ca 2+ efflux from saponin-permeabilized DDT 1 MF-2 cells was observed with the addition of either the α 1 -adrenergic agonist phenylephrine and guanosine-5'-triphosphate or the nonhydrolyzable guanine nucleotide guanylyl-imidodiphosphate. In the presence of [ 32 P] NAD, pertussis toxin was found to catalyze ADP-ribosylation of a M/sub r/ = 40,500 (n = 8) peptide in membranes prepared from DDT 1 , MF-2 cells, possibly the α-subunit of N/sub i/. However, stimulation of unidirectional 45 Ca 2+ efflux by phenylephrine was not affected by previous treatment of cells with 100 ng/ml pertussis toxin. These data suggest that the putative guanine nucleotide-binding protein which couples the α 1 -adrenergic receptor to Ca 2+ mobilization in DDT 1 MF-2 cells is not a pertussis toxin substrate and may possibly be an additional member of guanine nucleotide binding protein family

  12. Evaluation of a novel Arg-Gly-Asp-conjugated α-melanocyte stimulating hormone hybrid peptide for potential melanoma therapy.

    Science.gov (United States)

    Yang, Jianquan; Guo, Haixun; Gallazzi, Fabio; Berwick, Marianne; Padilla, R Steven; Miao, Yubin

    2009-08-19

    The purpose of this study was to determine whether Arg-Gly-Asp (RGD)-conjugated α-melanocyte stimulating hormone (α-MSH) hybrid peptide could be employed to target melanocortin-1 (MC1) receptor for potential melanoma therapy. The RGD motif {cyclic(Arg-Gly-Asp-DTyr-Asp)} was coupled to [Cys(3,4,10), DPhe(7), Arg(11)]α-MSH(3-13) {(Arg(11))CCMSH} to generate RGD-Lys-(Arg(11))CCMSH hybrid peptide. The MC1 receptor binding affinity of RGD-Lys-(Arg(11))CCMSH was determined in B16/F1 melanoma cells. The internalization and efflux, melanoma targeting and pharmacokinetic properties and single photon emission computed tomography/CT (SPECT/CT) imaging of (99m)Tc-RGD-Lys-(Arg(11))CCMSH were determined in B16/F1 melanoma cells and melanoma-bearing C57 mice. Clonogenic cytotoxic effect of RGD-Lys-(Arg(11))CCMSH was examined in B16/F1 melanoma cells. RGD-Lys-(Arg(11))CCMSH displayed 2.1 nM MC1 receptor binding affinity. (99m)Tc-RGD-Lys-(Arg(11))CCMSH showed rapid internalization and extended retention in B16/F1 cells. The cellular uptake of (99m)Tc-RGD-Lys-(Arg(11))CCMSH was MC1 receptor-mediated. (99m)Tc-RGD-Lys-(Arg(11))CCMSH exhibited high tumor uptake (14.83 ± 2.94% ID/g 2 h postinjection) and prolonged tumor retention (7.59 ± 2.04% ID/g 24 h postinjection) in B16/F1 melanoma-bearing mice. Nontarget organ uptakes were generally low except for the kidneys. Whole-body clearance of (99m)Tc-RGD-Lys-(Arg(11))CCMSH was rapid, with approximately 62% of the injected radioactivity cleared through the urinary system by 2 h postinjection. Flank melanoma tumors were clearly imaged by small animal SPECT/CT using (99m)Tc-RGD-Lys-(Arg(11))CCMSH as an imaging probe 2 h postinjection. Single treatment (3 h incubation) with 100 nM of RGD-Lys-(Arg(11))CCMSH significantly (p < 0.05) decreased the clonogenic survival of B16/F1 cells by 65% compared to the untreated control cells. Favorable melanoma targeting property of (99m)Tc-RGD-Lys-(Arg(11))CCMSH and remarkable cytotoxic effect of RGD

  13. Thyroid iodine uptake and serum triiodothyronine level in eldery subjects

    International Nuclear Information System (INIS)

    Paradowski, L.; Dolinska, G.; Knapik, Z.; Rynowiecka, M.

    1980-01-01

    Iodine uptake by the thyroid and serum triiodothyronine (T 3 ) level in subjects aged from 65 to 93 years were determined. Low T 3 level and normal uptake of inorganic iodine by the thyroid were found. In the light of these results it is suggested that normal accumulation of inorganic iodine and low production of T 3 are characteristic features of euthyroidism in elderly subjects. It is believed that the function of the thyroid is expressed better by determination of the serum levels of thyroid hormones than determination of the uptake of radioactive iodine. Elaboration of standard normal values which would take into account abnormalities encountered in old age is postulated. (author)

  14. Menopause and Hormones

    Science.gov (United States)

    ... Consumer Information by Audience For Women Menopause and Hormones: Common Questions Share Tweet Linkedin Pin it More ... reproduction and distribution. Learn More about Menopause and Hormones Menopause--Medicines to Help You Links to other ...

  15. Thyroid Hormone Treatment

    Science.gov (United States)

    ... THYROID HORMONES? Desiccated ( dried and powdered ) animal thyroid ( Armour ®), now mainly obtained from pigs, was the most ... hormone can increase the risk or heart rhythm problems and bone loss making the use of thyroxine ...

  16. Antidiuretic hormone blood test

    Science.gov (United States)

    ... medlineplus.gov/ency/article/003702.htm Antidiuretic hormone blood test To use the sharing features on this page, please enable JavaScript. Antidiuretic blood test measures the level of antidiuretic hormone (ADH) in ...

  17. Hormonal effects in newborns

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/001911.htm Hormonal effects in newborns To use the sharing features on this page, please enable JavaScript. Hormonal effects in newborns occur because in the womb, babies ...

  18. Growth hormone stimulation test

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003377.htm Growth hormone stimulation test To use the sharing features on this page, please enable JavaScript. The growth hormone (GH) stimulation test measures the ability of ...

  19. Thyroid uptake test

    International Nuclear Information System (INIS)

    Ganatra, R.D.

    1992-01-01

    The uptake of radioiodine by the thyroid gland is altered by the iodine content of diet or drugs. American diet has a high iodine content because each slice of the white bread contains nearly 150μg of iodine due to the bleaching process employed in the production of the bread. This carrier content of iodine reduces the uptake so much, that the normal American uptakes are usually three to four times lower than the uptakes in the developing countries. The other drawback of the thyroid uptake test is that it is affected by the iodine containing drugs. Anti-diarrhoea medications are quire common in the developing countries and many of them contain iodine moiety. Without a reliable drug history, a low thyroid uptake value may lead to a misleading conclusion

  20. Thyroid hormone uptake by rat hepatocytes in primary culture

    NARCIS (Netherlands)

    E.P. Krenning (Eric)

    1983-01-01

    textabstractIodide is taken up by the thyroid follicular cell, oxydized and bound to thyroglobulin at the apical membrane facing the colloid in the follicular lumen. Iodinated colloid is subsequently engulfed by the follicular cell and hydrolysed, liberating thyroxine and triiodothyronine from their

  1. ATP storage and uptake by isolated pancreatic zymogen granules

    DEFF Research Database (Denmark)

    Haanes, Kristian Agmund; Novak, Ivana

    2010-01-01

    ATP is released from pancreatic acini in response to cholinergic and hormonal stimulation. The same stimuli cause exocytosis of ZG (zymogen granules) and release of digestive enzymes. The aim of the present study was to determine whether ZG stored ATP and to characterize the uptake mechanism for ...

  2. The Effect of a Shear Flow on the Uptake of LDL and Ac-LDL by Cultured Vascular Endothelial Cells

    Science.gov (United States)

    Niwa, Koichi; Karino, Takeshi

    The effects of a shear flow on the uptake of fluorescence-labeled low-density lipoprotein (DiI-LDL), acetylated LDL (DiI-Ac-LDL), and lucifer yellow (LY; a tracer of fluid-phase endocytosis) by cultured bovine aortic ECs were studied using a rotating-disk shearing apparatus. It was found that 2hours’ exposure of ECs to a laminar shear flow that imposed ECs an area-mean shear stress of 10dynes/cm2 caused an increase in the uptake of DiI-LDL and LY. By contrast, the uptake of DiI-Ac-LDL was decreased by exposure of the ECs to a shear flow. Addition of dextran sulfate (DS), a competitive inhibitor of scavenger receptors, reversed the effect of a shear flow on the uptake of DiI-Ac-LDL, resulting in an increase by the imposition of a shear flow, while the uptake of DiI-LDL and LY remained unaffected. It was concluded that a shear flow promotes the endocytosis of DiI-LDL and LY by ECs, but suppresses the uptake of DiI-Ac-LDL by ECs by inhibiting scavenger receptor-mediated endocytosis.

  3. CB1 receptor-mediated signaling underlies the hippocampal synaptic, learning, and memory deficits following treatment with JWH-081, a new component of spice/K2 preparations.

    Science.gov (United States)

    Basavarajappa, Balapal S; Subbanna, Shivakumar

    2014-02-01

    Recently, synthetic cannabinoids have been sprayed onto plant material, which is subsequently packaged and sold as "Spice" or "K2" to mimic the effects of marijuana. A recent report identified several synthetic additives in samples of "Spice/K2", including JWH-081, a synthetic ligand for the cannabinoid receptor 1 (CB1). The deleterious effects of JWH-081 on brain function are not known, particularly on CB1 signaling, synaptic plasticity, learning and memory. Here, we evaluated the effects of JWH-081 on pCaMKIV, pCREB, and pERK1/2 signaling events followed by long-term potentiation (LTP), hippocampal-dependent learning and memory tasks using CB1 receptor wild-type (WT) and knockout (KO) mice. Acute administration of JWH-081 impaired CaMKIV phosphorylation in a dose-dependent manner, whereas inhibition of CREB phosphorylation in CB1 receptor WT mice was observed only at higher dose of JWH-081 (1.25 mg/kg). JWH-081 at higher dose impaired CaMKIV and CREB phosphorylation in a time-dependent manner in CB1 receptor WT mice but not in KO mice and failed to alter ERK1/2 phosphorylation. In addition, SR treated or CB1 receptor KO mice have a lower pCaMKIV/CaMKIV ratio and higher pCREB/CREB ratio compared with vehicle or WT littermates. In hippocampal slices, JWH-081 impaired LTP in CB1 receptor WT but not in KO littermates. Furthermore, JWH-081 at higher dose impaired object recognition, spontaneous alternation and spatial memory on the Y-maze in CB1 receptor WT mice but not in KO mice. Collectively our findings suggest that deleterious effects of JWH-081 on hippocampal function involves CB1 receptor mediated impairments in CaMKIV and CREB phosphorylation, LTP, learning and memory in mice. © 2013 Wiley Periodicals, Inc.

  4. Ultrastructural evidence for the accumulation of insulin in nuclei of intact 3T3-L1 adipocytes by an insulin-receptor mediated process

    International Nuclear Information System (INIS)

    Smith, R.M.; Jarett, L.

    1987-01-01

    Monomeric ferritin-labeled insulin (F/sub m/-Ins), a biologically active, electron-dense marker of occupied insulin receptors, was used to characterize the internalization of insulin in 3T3-L1 adipocytes. F/sub m/-Ins bound specifically to insulin receptors and was internalized in a time- and temperature-dependent manner. In the nucleus, several F/sub m/-Ins particles usually were found in the same general location-near nuclear pores, associated with the periphery of the condensed chromatin. Addition of a 250-fold excess of unlabeled insulin or incubation at 15 0 C reduced the number of F/sub m/-Ins particles found in nuclei after 90 min by 99% or 92%, respectively. Nuclear accumulation of unlabeled ferritin was only 2% of that found with F/sub m/-Ins after 90 min at 37 0 C. Biochemical experiments utilizing 125 I-labeled insulin and subcellular fractionation indicated that intact 3T3-L1 adipocytes internalized insulin rapidly and that ≅ 3% of the internalized ligand accumulated in nuclei after 1 hr. These data provide biochemical and high-resolution ultrastructural evidence that 3T3-L1 adipocytes accumulate potentially significant amounts of insulin in nuclei by an insulin receptor-mediated process. The transport of insulin or the insulin-receptor complex to nuclei in this cell or in others may be directly involved in the long-term biological effects of insulin - in particular, in the control of DNA and RNA synthesis

  5. Flavonoid rutin increases thyroid iodide uptake in rats.

    Directory of Open Access Journals (Sweden)

    Carlos Frederico Lima Gonçalves

    Full Text Available Thyroid iodide uptake through the sodium-iodide symporter (NIS is not only an essential step for thyroid hormones biosynthesis, but also fundamental for the diagnosis and treatment of different thyroid diseases. However, part of patients with thyroid cancer is refractory to radioiodine therapy, due to reduced ability to uptake iodide, which greatly reduces the chances of survival. Therefore, compounds able to increase thyroid iodide uptake are of great interest. It has been shown that some flavonoids are able to increase iodide uptake and NIS expression in vitro, however, data in vivo are lacking. Flavonoids are polyhydroxyphenolic compounds, found in vegetables present in human diet, and have been shown not only to modulate NIS, but also thyroperoxidase (TPO, the key enzyme in thyroid hormones biosynthesis, besides having antiproliferative effect in thyroid cancer cell lines. Therefore, we aimed to evaluate the effect of some flavonoids on thyroid iodide uptake in Wistar rats in vivo. Among the flavonoids tested, rutin was the only one able to increase thyroid iodide uptake, so we decided to evaluate the effect of this flavonoid on some aspects of thyroid hormones synthesis and metabolism. Rutin led to a slight reduction of serum T4 and T3 without changes in serum thyrotropin (TSH, and significantly increased hypothalamic, pituitary and brown adipose tissue type 2 deiodinase and decreased liver type 1 deiodinase activities. Moreover, rutin treatment increased thyroid iodide uptake probably due to the increment of NIS expression, which might be secondary to increased response to TSH, since TSH receptor expression was increased. Thus, rutin might be useful as an adjuvant in radioiodine therapy, since this flavonoid increased thyroid iodide uptake without greatly affecting thyroid function.

  6. Insulin-like growth factor 1: common mediator of multiple enterotrophic hormones and growth factors.

    Science.gov (United States)

    Bortvedt, Sarah F; Lund, P Kay

    2012-03-01

    To summarize the recent evidence that insulin-like growth factor 1 (IGF1) mediates growth effects of multiple trophic factors and discuss clinical relevance. Recent reviews and original reports indicate benefits of growth hormone (GH) and long-acting glucagon-like peptide 2 (GLP2) analogs in short bowel syndrome and Crohn's disease. This review highlights the evidence that biomarkers of sustained small intestinal growth or mucosal healing and evaluation of intestinal epithelial stem cell biomarkers may improve clinical measures of intestinal growth or response to trophic hormones. Compelling evidence that IGF1 mediates growth effects of GH and GLP2 on intestine or linear growth in preclinical models of resection or Crohn's disease is presented, along with a concept that these hormones or IGF1 may enhance sustained growth if given early after bowel resection. Evidence that suppressor of cytokine signaling protein induction by GH or GLP2 in normal or inflamed intestine may limit IGF1-induced growth, but protect against risk of dysplasia or fibrosis, is reviewed. Whether IGF1 receptor mediates IGF1 action and potential roles of insulin receptors are addressed. IGF1 has a central role in mediating trophic hormone action in small intestine. Better understanding of benefits and risks of IGF1, receptors that mediate IGF1 action, and factors that limit undesirable growth are needed.

  7. Thyroid Scan and Uptake

    Medline Plus

    Full Text Available Toggle navigation Test/Treatment Patient Type Screening/Wellness Disease/Condition Safety En Español More Info Images/Videos About Us News Physician ... of nuclear medicine imaging. The radioactive iodine uptake test (RAIU) is also known as a thyroid uptake. ...

  8. Thyroid Scan and Uptake

    Medline Plus

    Full Text Available Toggle navigation Test/Treatment Patient Type Screening/Wellness Disease/Condition Safety En Español More Info Images/Videos About Us News Physician Resources Professions Site Index A-Z Thyroid Scan and Uptake Thyroid scan and uptake uses ...

  9. Temporal aspects of copper homeostasis and its crosstalk with hormones

    Directory of Open Access Journals (Sweden)

    Lola ePeñarrubia

    2015-04-01

    Full Text Available To cope with the dual nature of copper as being essential and toxic for cells, plants temporarily adapt the expression of copper homeostasis components to assure its delivery to cuproproteins while avoiding the interference of potential oxidative damage derived from both copper uptake and photosynthetic reactions during light hours. The circadian clock participates in the temporal organization of coordination of plant nutrition adapting metabolic responses to the daily oscillations. This timely control improves plant fitness and reproduction and holds biotechnological potential to drive increased crop yields. Hormonal pathways, including those of abscisic acid, gibberellins, ethylene, auxins, and jasmonates are also under direct clock and light control, both in mono and dicotyledons. In this review, we focus on copper transport in Arabidopsis thaliana and Oryza sativa and the presumable role of hormones in metal homeostasis matching nutrient availability to growth requirements and preventing metal toxicity. The presence of putative hormone-dependent regulatory elements in the promoters of copper transporters genes suggests hormonal regulation to match special copper requirements during plant development. Spatial and temporal processes that can be affected by hormones include the regulation of copper uptake into roots, intracellular trafficking and compartmentalisation, and long-distance transport to developing vegetative and reproductive tissues. In turn, hormone biosynthesis and signalling are also influenced by copper availability, which suggests reciprocal regulation subjected to temporal control by the central oscillator of the circadian clock. This transcriptional regulatory network, coordinates environmental and hormonal signalling with developmental pathways to allow enhanced micronutrient acquisition efficiency.

  10. Studies on the mechanism of quinone action on hormonal regulation of metabolism in the rat liver

    International Nuclear Information System (INIS)

    Cheng, E.Y.

    1989-01-01

    The mechanism of quinone actions in liver cell metabolism had been investigated using menadione as a model compound. Previous reports suggested that quinones and free radicals could produce perturbations in cellular calcium homeostasis. Since calcium plays an important role in the regulation of cellular metabolic processes, then regulation of cytosolic calcium concentrations, and thus of cellular metabolism, by calcium-mobilizing hormones such as phenylephrine and vasopressin could possibly be modified by quinones such as menadione. Methods used to approach this hypothesis included the assay for activation of glycogen phosphorylase, an indirect index of calcium mobilization; the determination of calcium mobilization with 45 Ca efflux exchange and with fluorescent calcium indicator fura-2; and the measurement of phosphatidylinositides, an important link in the membrane-associated receptor-mediated signal transduction mechanism

  11. Growth hormone-releasing factor stimulates proliferation of somatotrophs in vitro

    DEFF Research Database (Denmark)

    Billestrup, Nils; Swanson, L W; Vale, W

    1986-01-01

    The mitogenic effect of the hypothalamic peptides growth hormone-releasing factor (GRF) and somatostatin on cultured growth hormone (GH)-producing cells (somatotrophs) was studied. Using autoradiographic detection of [3H]thymidine uptake and immunocytochemical identification of GH-producing cells...

  12. In vitro comparison of renal handling and uptake of two somatostatin receptor-specific peptides labeled with indium-111

    International Nuclear Information System (INIS)

    Trejtnar, F.; Novy, Z.; Petrik, M.; Laznickova, A.; Melicharova, L.; Vankova, M.; Laznicek, M.

    2008-01-01

    Radiolabeled receptor-specific somatostatin analogs labeled with gamma- or beta-emitting radionuclides are useful for scintigraphic imaging and/or therapy of selected neuroendocrine tumors. However, significant renal uptake may result in radiotoxicological injury of the kidney and can limit clinical application of the agents. The aim of the study was to analyze renal handling, rate, and mechanism of renal accumulation of two somatostatin receptor-targeted peptides, [DOTA 0 , Tyr 3 , Thr 8 ]-octreotide (DOTA-TATE) and [DOTA 0 , 1-Nal 3 ]-octreotide (DOTA-NOC), labeled with indium-111 using in vitro methods. The perfused rat kidney and freshly isolated rat renal cells were used as experimental models. The perfusion was performed in a recirculation regimen at constant pressure with solution containing bovine albumin, erythrocytes, and a mixture of essential substrates. The renal cells were isolated from rat kidneys using two-phase collagenase perfusion. Accumulation studies were used to evaluate the renal uptake of the peptides and to compare their accumulation with that of passively or actively transported model drugs. The influence of selected inhibitors of receptor-mediated endocytosis and the inhibition of energy-dependent transport processes on the uptake were also investigated using isolated renal cells. The renal clearance of 111 In-DOTA-NOC in the perfused rat kidney was significantly lower than that of 111 In-DOTA-TATE. Reverse situation was found in the case of renal retention. Pretreatment of the perfused kidney with maleate markedly decreased the renal retention. 111 In-DOTA-NOC was accumulated in the isolated renal cells at a higher rate than 111 In-DOTA-TATE (ratio 3:1). The uptake of the radiopeptides in renal cells was higher than the uptake of not only the passively transported sucrose but also actively transported and accumulated methylglucose. The rank order of potency to inhibit the uptake by active endocytosis was approximately aprotinin

  13. Orexin A/Hypocretin Modulates Leptin Receptor-Mediated Signaling by Allosteric Modulations Mediated by the Ghrelin GHS-R1A Receptor in Hypothalamic Neurons.

    Science.gov (United States)

    Medrano, Mireia; Aguinaga, David; Reyes-Resina, Irene; Canela, Enric I; Mallol, Josefa; Navarro, Gemma; Franco, Rafael

    2018-06-01

    The hypothalamus is a key integrator of nutrient-seeking signals in the form of hormones and metabolites originated in both the central nervous system and the periphery. The main autocrine and paracrine target of orexinergic-related hormones such as leptin, orexin/hypocretin, and ghrelin are neuropeptide Y neurons located in the arcuate nucleus of the hypothalamus. The aim of this study was to investigate the expression and the molecular and functional relationships between leptin, orexin/hypocretin and ghrelin receptors. Biophysical studies in a heterologous system showed physical interactions between them, with potential formation of heterotrimeric complexes. Functional assays showed robust allosteric interactions particularly different when the three receptors are expressed together. Further biochemical and pharmacological assays provided evidence of heterotrimer functional expression in primary cultures of hypothalamic neurons. These findings constitute evidence of close relationships in the action of the three hormones already starting at the receptor level in hypothalamic cells.

  14. Steroid hormone receptors: long- and short-term integrators of the internal milieu and the external environment.

    Science.gov (United States)

    Blaustein, J D

    2012-07-01

    Many of the influences of estrogens and progestins on the brain and behavior are mediated by estrogen receptors and progestin receptors, acting as transcriptional regulators. The homologous and heterologous regulation of the concentrations of these receptors by cognate hormones is well established. However, although they were discovered and characterized based on their binding to cognate hormone and their role in transcriptional regulation, steroid hormone receptors have a more complex role and serve many more functions than originally suspected. First, besides being regulated by steroid hormones, the intracellular concentrations of brain steroid hormone receptors are regulated by neurotransmitters, a pathway by which stimuli from the environment, including from conspecific animals, can modulate the concentration of particular steroid hormone receptors in subsets of cells. Further, besides being activated by cognate steroid hormones, the receptors can be activated by a variety of neurotransmitters and phosphorylation pathways, providing a route through which environmental stimulation can activate steroid-receptor-dependent functions in specific cells. In addition, the transcription factor, estrogen receptor-α, produced from the estrogen receptor-α gene, can be modified to be targeted to membranes, where it can signal via kinase pathways. Finally, developmental experiences, such as particular stressors during the pubertal period, can permanently remodel the brain's response to ovarian hormones, most likely by long-term changes in regulation of the receptors mediating those responses. In addition to their function in responding to cognate ligand, it is now more appropriate to think of steroid hormone receptors as integrators of a wide variety of signaling pathways. © Georg Thieme Verlag KG Stuttgart · New York.

  15. P2Y receptor-mediated transient relaxation of rat longitudinal ileum preparations involves phospholipase C activation, intracellular Ca(2+) release and SK channel activation.

    Science.gov (United States)

    Mader, Felix; Krause, Ludwig; Tokay, Tursonjan; Hakenberg, Oliver W; Köhling, Rüdiger; Kirschstein, Timo

    2016-05-01

    Purinergic signaling plays a major role in the enteric nervous system, where it governs gut motility through a number of P2X and P2Y receptors. The aim of this study was to investigate the P2Y receptor-mediated motility in rat longitudinal ileum preparations. Ileum smooth muscle strips were prepared from rats, and fixed in an organ bath. Isometric contraction and relaxation responses of the muscle strips were measured with force transducers. Drugs were applied by adding of stock solutions to the organ bath to yield the individual final concentrations. Application of the non-hydrolyzable P2 receptor agonists α,β-Me-ATP or 2-Me-S-ADP (10, 100 μmol/L) dose-dependently elicited a transient relaxation response followed by a sustained contraction. The relaxation response was largely blocked by SK channel blockers apamin (500 nmol/L) and UCL1684 (10 μmol/L), PLC inhibitor U73122 (100 μmol/L), IP3 receptor blocker 2-APB (100 μmol/L) or sarcoendoplasmic Ca(2+) ATPase inhibitor thapsigargin (1 μmol/L), but not affected by atropine, NO synthase blocker L-NAME or tetrodotoxin. Furthermore, α,β-Me-ATP-induced relaxation was suppressed by P2Y1 receptor antagonist MRS2179 (50 μmol/L) or P2Y13 receptor antagonist MRS2211 (100 μmol/L), and was abolished by co-application of the two antagonists, whereas 2-Me-S-ADP-induced relaxation was abolished by P2Y6 receptor antagonist MRS2578 (50 μmol/L). In addition, P2Y1 receptor antagonist MRS2500 (1 μmol/L) not only abolished α,β-Me-ATP-induced relaxation, but also suppressed 2-Me-S-ADP-induced relaxation. P2Y receptor agonist-induced transient relaxation of rat ileum smooth muscle strips is mediated predominantly by P2Y1 receptor, but also by P2Y6 and P2Y13 receptors, and involves PLC, IP3, Ca(2+) release and SK channel activation, but is independent of acetylcholine and NO release.

  16. Dopamine D2 receptor-mediated G-protein activation in rat striatum: functional autoradiography and influence of unilateral 6-hydroxydopamine lesions of the substantia nigra.

    Science.gov (United States)

    Newman-Tancredi, A; Cussac, D; Brocco, M; Rivet, J M; Chaput, C; Touzard, M; Pasteau, V; Millan, M J

    2001-11-30

    , the present data indicate that, in rat striatum, the actions of quinelorane are mediated primarily by D2 receptors, and suggest that behavioural hypersensitivity to this agonist, induced by unilateral SNPC lesions, is associated with an increase in D2, but not D3 or D4, receptor-mediated G-protein activation.

  17. Role of G3BP1 in glucocorticoid receptor-mediated microRNA-15b and microRNA-23a biogenesis in endothelial cells

    KAUST Repository

    Kwok, Hoi-Hin; Poon, Po-Ying; Mak, Kylie Hin-Man; Zhang, Lin-Yao; Liu, Pei; Zhang, Huoming; Mak, Nai-Ki; Yue, Patrick Ying-Kit; Wong, Ricky Ngok-Shun

    2017-01-01

    MicroRNAs (miRNAs) are a family of non-coding RNAs that play crucial roles in regulating various normal cellular responses. Recent studies revealed that the canonical miRNA biogenesis pathway is subject to sophisticated regulation. Hormonal control

  18. Thyroid Scan and Uptake

    Medline Plus

    Full Text Available ... information about your thyroid’s size, shape, position and function that is often unattainable using other imaging procedures. ... thyroid uptake. It is a measurement of thyroid function, but does not involve imaging. Nuclear medicine is ...

  19. Thyroid Scan and Uptake

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    Full Text Available ... which are encased in metal and plastic and most often shaped like a box, attached to a ... will I experience during and after the procedure? Most thyroid scan and thyroid uptake procedures are painless. ...

  20. Thyroid Scan and Uptake

    Medline Plus

    Full Text Available ... eat for several hours before your exam because eating can affect the accuracy of the uptake measurement. ... often unattainable using other imaging procedures. For many diseases, nuclear medicine scans yield the most useful information ...

  1. Thyroid Scan and Uptake

    Medline Plus

    Full Text Available ... A thyroid scan is a type of nuclear medicine imaging. The radioactive iodine uptake test (RAIU) is ... thyroid function, but does not involve imaging. Nuclear medicine is a branch of medical imaging that uses ...

  2. Thyroid Scan and Uptake

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    Full Text Available ... Because nuclear medicine procedures are able to pinpoint molecular activity within the body, they offer the potential ... or imaging device that produces pictures and provides molecular information. The thyroid scan and thyroid uptake provide ...

  3. Thyroid Scan and Uptake

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    Full Text Available ... Actual scanning time for each thyroid uptake is five minutes or less. top of page What will ... diagnostic procedures have been used for more than five decades, and there are no known long-term ...

  4. Thyroid Scan and Uptake

    Medline Plus

    Full Text Available ... top of page Additional Information and Resources RTAnswers.org Radiation Therapy for Head and Neck Cancer top ... Scan and Uptake Sponsored by Please note RadiologyInfo.org is not a medical facility. Please contact your ...

  5. Thyroid Scan and Uptake

    Medline Plus

    Full Text Available ... When radiotracer is taken by mouth, in either liquid or capsule form, it is typically swallowed up ... radioactive iodine (I-123 or I-131) in liquid or capsule form to swallow. The thyroid uptake ...

  6. Thyroid Scan and Uptake

    Medline Plus

    Full Text Available ... RAIU) is also known as a thyroid uptake. It is a measurement of thyroid function, but does ... they offer the potential to identify disease in its earliest stages as well as a patient’s immediate ...

  7. Thyroid Scan and Uptake

    Medline Plus

    Full Text Available ... for several hours before your exam because eating can affect the accuracy of the uptake measurement. Jewelry ... small hand-held device resembling a microphone that can detect and measure the amount of the radiotracer ...

  8. Thyroid Scan and Uptake

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    Full Text Available ... of page What will I experience during and after the procedure? Most thyroid scan and thyroid uptake ... you otherwise, you may resume your normal activities after your nuclear medicine scan. If any special instructions ...

  9. Thyroid Scan and Uptake

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    Full Text Available ... scan and thyroid uptake provide information about the structure and function of the thyroid. The thyroid is ... computer, create pictures offering details on both the structure and function of organs and tissues in your ...

  10. Thyroid Scan and Uptake

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    Full Text Available ... eat for several hours before your exam because eating can affect the accuracy of the uptake measurement. ... its radioactivity over time. It may also pass out of your body through your urine or stool ...

  11. Thyroid Scan and Uptake

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    Full Text Available ... procedures within the last two months that used iodine-based contrast material. Your doctor will instruct you ... a type of nuclear medicine imaging. The radioactive iodine uptake test (RAIU) is also known as a ...

  12. FAT/CD36 expression alone is insufficient to enhance cellular uptake of oleate

    International Nuclear Information System (INIS)

    Eyre, Nicholas S.; Cleland, Leslie G.; Mayrhofer, Graham

    2008-01-01

    Fatty acid translocase (FAT/CD36) is one of several proteins implicated in receptor-mediated uptake of long-chain fatty acids (LCFAs). We have tested whether levels of FAT/CD36 correlate with cellular oleic acid import, using a Tet-Off inducible transfected CHO cell line. Consistent with our previous findings, FAT/CD36 was enriched in lipid raft-derived detergent-resistant membranes (DRMs) that also contained caveolin-1, the marker protein of caveolae. Furthermore in transfected cells, plasma membrane FAT/CD36 co-localized extensively with the lipid raft-enriched ganglioside GM1, and partially with a caveolin-1-EGFP fusion protein. Nevertheless, even at high levels of expression, FAT/CD36 did not affect uptake of oleic acid. We propose that the ability of FAT/CD36 to mediate enhanced uptake of LCFAs is dependent on co-expression of other proteins or factors that are lacking in CHO cells

  13. Thyroid hormones regulate selenoprotein expression and selenium status in mice.

    Directory of Open Access Journals (Sweden)

    Jens Mittag

    Full Text Available Impaired expression of selenium-containing proteins leads to perturbed thyroid hormone (TH levels, indicating the central importance of selenium for TH homeostasis. Moreover, critically ill patients with declining serum selenium develop a syndrome of low circulating TH and a central downregulation of the hypothalamus-pituitary-thyroid axis. This prompted us to test the reciprocal effect, i.e., if TH status would also regulate selenoprotein expression and selenium levels. To investigate the TH dependency of selenium metabolism, we analyzed mice expressing a mutant TH receptor α1 (TRα1+m that confers a receptor-mediated hypothyroidism. Serum selenium was reduced in these animals, which was a direct consequence of the mutant TRα1 and not related to their metabolic alterations. Accordingly, hyperthyroidism, genetically caused by the inactivation of TRβ or by oral TH treatment of adult mice, increased serum selenium levels in TRα1+m and controls, thus demonstrating a novel and specific role for TRα1 in selenium metabolism. Furthermore, TH affected the mRNA levels for several enzymes involved in selenoprotein biosynthesis as well as serum selenoprotein P concentrations and the expression of other antioxidative selenoproteins. Taken together, our results show that TH positively affects the serum selenium status and regulates the expression of several selenoproteins. This demonstrates that selenium and TH metabolism are interconnected through a feed-forward regulation, which can in part explain the rapid parallel downregulation of both systems in critical illness.

  14. The metabotropic glutamate receptor agonist 1S,3R-ACPD stimulates and modulates NMDA receptor mediated excitotoxicity in organotypic hippocampal slice cultures

    DEFF Research Database (Denmark)

    Blaabjerg, M; Kristensen, Bjarne Winther; Bonde, C

    2001-01-01

    the PI uptake in both CA1 and CA3, compared to cultures exposed to 10 microM NMDA only. Adding the 300 microM ACPD as pretreatment for 30 min followed by a 30 min wash in normal medium before the ACPD/NMDA co-exposure, eliminated the potentiation of NMDA toxicity. The potentiation was also blocked...

  15. Role of calcium in gonadotropin releasing hormone-induced luteinizing hormone secretion from the bovine pituitary

    International Nuclear Information System (INIS)

    Kile, J.P.

    1986-01-01

    The hypothesis was tested that GnRH acts to release LH by increasing calcium uptake by gonadotroph which in turn stimulates calcium-calmodulin activity and results in LH release from bovine pituitary cells as it does in the rat. Pituitary glands of calves (4-10 months of age) were enzymatically dispersed (0.2% collagenase) and grown for 5 days to confluency in multiwell plates (3 x 10 5 /well). Cells treated with GnRH Ca ++ ionophore A23187, and ouabain all produced significant releases of LH release in a pronounced all or none fashion, while thorough washing of the cells with 0.5 mM EGTA in Ca ++ -free media prevented the action of GnRH. GnRH caused a rapid efflux of 45 Ca ++ . Both GnRH-stimulated 45 Ca efflux and LH release could be partially blocked by verapamil GnRH-induced LH release could also be blocked by nifedipine and tetrodotoxin, although these agents did not affect 45 Ca efflux. The calmodulin antagonists calmidazolium and W7 were found to block GnRH induced LH release, as well as LH release induced by theophylline, KC PGE 2 and estradiol. These data indicated that: (1) calcium is required for GnRH action, but extracellular Ca ++ does not regulate LH release; (2) GnRH elevates intracellular Ca ++ by opening both voltage sensitive and receptor mediated Ca ++ channels; (3) activation of calmodulin is one mechanism involved in GnRH-induced LH release

  16. Metabolism of labeled parathyroid hormone. V. Collected biological studies

    Energy Technology Data Exchange (ETDEWEB)

    Neuman, W F; Neuman, M W; Lane, K; Miller, L; Sammon, P J

    1975-01-01

    Biologically active /sup 125/I-labeled parathyroid hormone (/sup 125/I-PTH) was used in a series of studies in dogs and chickens designed to confirm and augment earlier studies in rats. As in rats, a three exponential equation was required to describe disappearance of /sup 125/I-PTH from the blood in the dog. The first two ''half-lives'' (1.8 and 7 min) accounted for the bulk of the dose. Also as in rats, deposition of apparently intact hormone took place rapidly in kidney, liver and bone in both the dog and the chicken. Degradation occurred very rapidly in all three target organs. Three labeled hormones of different biological activities were compared in the rat. Inactive, oxidized hormone was rejected by the liver but showed markedly increased deposition in kidney and the higher the purity of the hormone the higher was its uptake by liver. Exploration of a wide range of dosages revealed few effects on distribution (smaller depositon in liver and kidney at highest dosages, 65 ..mu..g/rat). Fresh sera did not degrade hormone rapidly or extensively. There was no deposition of hormone in intestinal mucosa, marrow, and red cells. Nephrectomy increased deposition in liver and bone. Finally, the perfused liver was capable of extensive degradation of the hormone.

  17. Molecular Basis for Certain Neuroprotective Effects of Thyroid Hormone

    Directory of Open Access Journals (Sweden)

    Paul eDavis

    2011-10-01

    Full Text Available The pathophysiology of brain damage that is common to ischemia-reperfusion inury and brain trauma includes disordered neuronal and glial cell energetics, intracellular acidosis, calcium toxicity, extracellular excitotoxic glutamate accumulation and dysfunction of the cytoskeleton and endoplasmic reticulum. Thyroid hormone isoforms, 3, 5, 3'-triiodo-L-thyronine (T3 and L-thyroxine (T4, have nongenomic and genomic actions that are relevant to repair of certain features of the pathophysiology of brain damage. Thyroid hormone can nongenomically repair intracullar H+ accumulation by stimulation of the Na+/H+ exchanger and can support desirably low [Ca2+]i.c. by activation of plasma membrane Ca2+-ATPase. Thyroid hormone nongenomically stimulates astrocyte glutamate uptake, an action that protects both glial cells and neurons. The hormone supports the integrity of the cytoskeleton by its effect on actin. Several proteins linked to thyroid hormone action are also neuroprotective. For example, the hormone stimulates expression of the seladin-1 gene whose gene product is anti-apoptotic and is potentially protection in the setting of neurodegeneration. Transthyretin (TTR is a serum transport protein for T4 that is important to blood-brain barrier transfer of the hormone and TTR has also been found to be neuroprotective in the setting of ischemia. Finally, the interesting thyronamine derivatives of T4 have been shown to protect against ischemic brain damage through their ability to induce hypothermia in the intact organism. Thus, thyroid hromone or hormone derivatives have experimental promise as neuroprotective agents.

  18. Radioimmunoassay of thyroid hormones

    International Nuclear Information System (INIS)

    Bartalena, L.; Mariotti, S.; Pinchera, A.

    1987-01-01

    For many years, methods based on iodine content determination have represented the only techniques available for the estimation of total thyroid hormone concentrations in serum. Subsequently, simple, sensitive, and specific radioligand assays for thyroid hormones have replaced these chemical methods. For the purpose of this chapter, iodometric techniques are only briefly summarized for their historical importance, whereas attention is focused on radioligand assays

  19. Adult growth hormone deficiency

    Directory of Open Access Journals (Sweden)

    Vishal Gupta

    2011-01-01

    Full Text Available Adult growth hormone deficiency (AGHD is being recognized increasingly and has been thought to be associated with premature mortality. Pituitary tumors are the commonest cause for AGHD. Growth hormone deficiency (GHD has been associated with neuropsychiatric-cognitive, cardiovascular, neuromuscular, metabolic, and skeletal abnormalities. Most of these can be reversed with growth hormone therapy. The insulin tolerance test still remains the gold standard dynamic test to diagnose AGHD. Growth hormone is administered subcutaneously once a day, titrated to clinical symptoms, signs and IGF-1 (insulin like growth factor-1. It is generally well tolerated at the low-doses used in adults. Pegylated human growth hormone therapy is on the horizon, with a convenient once a week dosing.

  20. Heart, lipids and hormones

    Directory of Open Access Journals (Sweden)

    Peter Wolf

    2017-05-01

    Full Text Available Cardiovascular disease is the leading cause of death in general population. Besides well-known risk factors such as hypertension, impaired glucose tolerance and dyslipidemia, growing evidence suggests that hormonal changes in various endocrine diseases also impact the cardiac morphology and function. Recent studies highlight the importance of ectopic intracellular myocardial and pericardial lipid deposition, since even slight changes of these fat depots are associated with alterations in cardiac performance. In this review, we overview the effects of hormones, including insulin, thyroid hormones, growth hormone and cortisol, on heart function, focusing on their impact on myocardial lipid metabolism, cardiac substrate utilization and ectopic lipid deposition, in order to highlight the important role of even subtle hormonal changes for heart function in various endocrine and metabolic diseases.

  1. Aging changes in hormone production

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/004000.htm Aging changes in hormone production To use the sharing ... that produce hormones are controlled by other hormones. Aging also changes this process. For example, an endocrine ...

  2. Hormonal changes in secondary impotence

    International Nuclear Information System (INIS)

    Salama, F.M.; El-Shabrawy, N.O.; Nosseir, S.A.; Abo El-Azayem, Naglaa.

    1985-01-01

    Impotence is one of the problems which is still obscure both in its aetiology and treatment. The present study deals with the possible hormonal changes in cases of secondary infertility. The study involved 25 patients diagnosed as secondary impotence. Hormonal assay was performed for the following hormones: 1. Prolaction hormone. 2. Luteinising hormone (L.H.). 3. Testosterone. 4. Follicle stimulating hormone (F.S.H.). The assay was carried out by radioimmunoassay using double antibody technique. Results are discussed

  3. Role of the metabolism of parathyroid hormone. [Rats

    Energy Technology Data Exchange (ETDEWEB)

    Teitelbaum, Anne P. [Univ. of Rochester, NY (United States)

    1978-01-01

    The heterogeneity of parathyroid hormone (PTH) in plasma has prompted investigations of the metabolism of PTH and its relationship to hormone action. The time course of tissue distribution and metabolism of electrolytically iodinated PTH (E-PTH) previously shown to retain biological activity was compared with that of inactive PTH iodinated with Chloramine-T (CT-PTH). Labeled PTH (0.4 μg) was injected in the saphenous veins of anesthetized rats which were sacrificed at 1, 3, 5, 10, and 20 min. Tissue extracts from kidney, liver, and serum were chromatographed to separate intact PTH from its metabolites. In the kidney, the initial rate of degradation of E-PTH was greater than that of CT-PTH. The difference in initial rates of metabolism may be due, in part, to receptor-specific hydrolysis on peritubular cell membranes which selectively act on biologically active PTH molecules. PTH-responsive adenyl cyclase activity in isolated kidney cortex plasma membranes was measured and PTH metabolism was monitored simultaneously. When degradation was completely blocked by histone f3 (1 mg/ml), adenyl cyclase activity was significantly increased over control. In addition, when adenyl cyclase activity was negligible, the rate of PTH degradation by the membranes was not significantly diminished. Consistent with the in vivo data was the observation that E-PTH is metabolized by these membranes at a greater rate than CT-PTH. The data demonstrate the existence of a receptor-specific metabolism at sites which are independent of PTH receptor mediated adenyl cyclase activity.

  4. Thyroid uptake software

    International Nuclear Information System (INIS)

    Alonso, Dolores; Arista, Eduardo

    2003-01-01

    The DETEC-PC software was developed as a complement to a measurement system (hardware) able to perform Iodine Thyroid Uptake studies. The software was designed according to the principles of Object oriented programming using C++ language. The software automatically fixes spectrometric measurement parameters and besides patient measurement also performs statistical analysis of a batch of samples. It possesses a PARADOX database with all information of measured patients and a help system with the system options and medical concepts related to the thyroid uptake study

  5. The rate of 99m Tc-MDP uptake in metastatic bone lesions before and after 89m Sr therapy

    International Nuclear Information System (INIS)

    Souza, Joseane Fonseca; Braga, Francisco J.H.N.

    1996-01-01

    The rate of 99m Tc-MDP uptake is studied in metastatic bone lesions, before and after 89m Sr therapy. Eight hopeless patients (age between 56 and 74) presenting disseminated carcinoma of the prostate are evaluated. No hormonal therapy and a limited radiotherapy were considered. It is concluded that therapeutical doses of 89m Sr reduces MDP uptake

  6. Effect of wortmannin and phorbol ester on Paramecium fluid-phase uptake in the presence of transferrin

    Directory of Open Access Journals (Sweden)

    J Wiejak

    2009-12-01

    Full Text Available The kinetics of the uptake of the fluid phase marker Lucifer Yellow (LY, and its alteration by wortmannin, an inhibitor of phosphatidylinositol-3 kinase (PI-3K, and the PKC modulators: GF 109203 X, an inhibitor, and phorbol ester, an activator was studied in eukaryotic model Paramecium aurelia. Spectrophotometric quantification of LY accumulation was performed in the presence or absence of transferrin, a marker of receptor-mediated endocytosis. Internalization of LY showed a curvilinear kinetics: the high initial rate of LYuptake (575 ng LY/ mg protein /hr decreased almost 5-fold within 15 min, reaching plateau at 126 ng/ mg protein /hr. Transferrin induced a small increase (7.5% in the fluid phase uptake rate (after 5 min followed by a small decrease at longer incubation times. Lucifer Yellow and transferrin (visualized by streptavidin– FITC were localized in Paramecium by 3-D reconstruction by confocal microscopy. LY showed a scattered, diffuse fluorescence typical of fluid phase uptake whereas transferrin accumulated in membrane-surrounded endosomes. Wortmannin did not affect LY accumulation but decreased it when transferrin was present in the incubation medium. This suggests an effect on the transferrin uptake pathway, presumably on the stage of internalization in “mixing” endosomes to which transferrin and LY were targeted. Phorbol ester diminished LY accumulation by 22% and this effect persisted up to 25 min of incubation. PKC inhibitor did not affect LY uptake. However, in the presence of transferrin, the LY uptake increased within the first 15 minutes followed by a rapid 20% decrease in comparison to the control. Such an effect of PKC modulators suggests that PMA action on fluid phase uptake is not directly mediated by PKC.

  7. Uptake of three [3H]progestins by target tissues in vivo: implications for the design of diagnostic imaging agents

    International Nuclear Information System (INIS)

    Carlson, K.E.; Brandes, S.J.; Pomper, M.G.; Katzenellenbogen, J.A.

    1988-01-01

    We have investigated the tissue distribution of radioactivity for 0.5-4 h following the i.v. injection of three tritium-labeled progestins in estrogen-primed, immature rats. Whereas [ 3 H]progesterone shows minimal uterine uptake ( 3 H]R 5020 (promegestrone) and [ 3 H]ORG 2058 show highly selective uptake that reaches 4-5% ID/g by 1-3 h. The uterus to non-target tissue activity ratio at 2-4 h is approximately 12-20 for R 5020 and ORG 2058, but less than 2 for progesterone; the uterus to blood activity ratio for R 5020 is also high (approximately 15), but is lower for ORG 2058, possibly due to the accumulation of radiolabeled metabolites in the blood. The uterine uptake is selectively blocked by simultaneous injection of a large dose of unlabeled steroid, indicating that the uptake is mediated by a high affinity, low capacity binding system, presumably the progesterone receptor. Pronounced uptake is also observed by the liver and into fat, but is not receptor-mediated. The highly selective target tissue uptake by the two synthetic steroids, but not by progesterone, indicates that one must have ligands with sufficiently high affinity for the target tissue receptor, as well as low affinity for certain non-receptor binding proteins, in order to obtain adequate contrast between target and non-target tissues in dynamic uptake studies. These guidelines will be important in the development of suitable in vivo imaging agents based on the progesterone receptor. (author)

  8. Thyroid Scan and Uptake

    Medline Plus

    Full Text Available Toggle navigation Test/Treatment Patient Type Screening/Wellness Disease/Condition Safety En Español More Info Images/Videos About Us News Physician Resources Professions Site Index A-Z Thyroid Scan and Uptake ...

  9. Thyroid Scan and Uptake

    Medline Plus

    Full Text Available ... information. The thyroid scan and thyroid uptake provide information about the structure and function of the thyroid. The thyroid is a gland in the neck that controls metabolism , a chemical process that regulates the rate at which the body ...

  10. Radioactive uptake by plants

    Energy Technology Data Exchange (ETDEWEB)

    Horak, O

    1986-01-01

    The fundamentals of radionuclide uptake by plants, both by leaves and roots are presented. Iodine, cesium, strontium and ruthenium are considered and a table of the measured concentrations in several agricultural plants shortly after the Chernobyl accident is presented. Another table gives the Cs and Sr transfer factors soil plants for some plants. By using them estimates of future burden can be obtained.

  11. Thyroid Scan and Uptake

    Medline Plus

    Full Text Available ... type your comment or suggestion into the following text box: Comment: E-mail: Area code: Phone no: ... of a typical probe counter used for thyroid uptake exams. The patient sits with the camera directed at the neck for five minutes, and then the leg for ...

  12. Thyroid Scan and Uptake

    Science.gov (United States)

    ... type your comment or suggestion into the following text box: Comment: E-mail: Area code: Phone no: ... of a typical probe counter used for thyroid uptake exams. The patient sits with the camera directed at the neck for five minutes, and then the leg for ...

  13. Hormones and Hypertension

    Science.gov (United States)

    ... role in the start and continuation of primary hypertension. Secondary hypertension is due to other diseases such as kidney ... the body can greatly improve or even cure secondary hypertension. Resources • Find-an-Endocrinologist: www.hormone.org or ...

  14. Growth hormone test

    Science.gov (United States)

    ... is called acromegaly . In children it is called gigantism . Too little growth hormone can cause a slow ... growth due to excess GH during childhood, called gigantism. (A special test is done to confirm this ...

  15. Clinical Significance of Diffuse Intrathoracic Uptake on Post-Therapy I-131 Scans in Thyroid Cancer Patients

    International Nuclear Information System (INIS)

    Choi, Hyun Su; Kim, Sung Hoon; Park, Sonya Youngju; Park, Hye Lim; Seo, Ye Young; Choi, Woo Hee

    2014-01-01

    The purpose of this study was to identify the frequency and possible cause of diffuse intrathoracic uptake on post-therapy I-131 scans in thyroid cancer patients. We retrospectively reviewed 781 post-therapy scans of 755 thyroid cancer patients who underwent total thyroidectomy and radioactive iodine therapy between January and December 2010. Diffuse intrathoracic uptake on post-therapy scans was examined, and clinical patient characteristics including sex, age, regimen for thyroid-stimulating hormone (TSH) stimulation (thyroid hormone withdrawal or recombinant human TSH injection), TSH, thyroglobulin (Tg) and anti-thyroglobulin antibody (anti-Tg Ab) levels, therapeutic dose of radioactive iodine therapy and prior history of radioactive iodine therapy were recorded.Scan findings were correlated with chest CT, chest radiographs, laboratory tests and/or clinical status. Diffuse intrathoracic uptake without evidence of pathologic condition was categorized as indeterminate. The association between clinical characteristics and intrathoracic uptake were analyzed for negative intrathoracic uptake and indeterminate uptake groups. Diffuse intrathoracic uptake on post-therapy scans was demonstrated in 39 out of 755 (5.2 %) patients, among which 3 were confirmed as lung metastasis. The 14 patients that showed high Tg or anti-Tg Ab levels were considered to be at risk of having undetected micrometastasis on other imaging modalities. The remaining 22 were indeterminate (2.9 %). Upon comparison of negative intrathoracic uptake and indeterminate uptake groups, TSH stimulation by thyroid hormone withdrawal was shown to be significantly correlated with diffuse intrathoracic uptake (p <0.05). The frequency of diffuse intrathoracic uptake on post-therapy scans was 5.2 % and could be seen in thyroid cancer patients with underlying lung metastasis as well as those without definite pathologic condition. In the latter, there was a higher frequency for diffusely increased intrathoracic

  16. Growth Hormone-Releasing Hormone in Diabetes

    Directory of Open Access Journals (Sweden)

    Leonid Evsey Fridlyand

    2016-10-01

    Full Text Available Growth hormone-releasing hormone (GHRH is produced by the hypothalamus and stimulates growth hormone synthesis and release in the anterior pituitary gland. In addition GHRH is an important regulator of cellular functions in many cells and organs. Expression of GHRH G-Protein Coupled Receptor (GHRHR has been demonstrated in different peripheral tissues and cell types including pancreatic islets. Among the peripheral activities, recent studies demonstrate a novel ability of GHRH analogs to increase and preserve insulin secretion by beta-cells in isolated pancreatic islets, which makes them potentially useful for diabetes treatment. This review considers the role of GHRHR in the beta-cell and addresses the unique engineered GHRH agonists and antagonists for treatment of Type 2 diabetes mellitus. We discuss the similarity of signaling pathways activated by GHRHR in pituitary somatotrophs and in pancreatic beta-cells and possible ways as to how the GHRHR pathway can interact with glucose and other secretagogues to stimulate insulin secretion. We also consider the hypothesis that novel GHRHR agonists can improve glucose metabolism in Type 2 diabetes by preserving the function and survival of pancreatic beta-cells. Wound healing and cardioprotective action with new GHRH agonists suggesting that they may prove useful in ameliorating certain diabetic complications. These findings highlight the future potential therapeutic effectiveness of modulators of GHRHR activity for the development of new therapeutic approaches in diabetes and its complications.

  17. Thyroid Stimulating Hormone Receptor

    Directory of Open Access Journals (Sweden)

    Murat Tuncel

    2017-02-01

    Full Text Available Thyroid stimulating hormone receptor (TSHR plays a pivotal role in thyroid hormone metabolism. It is a major controller of thyroid cell function and growth. Mutations in TSHR may lead to several thyroid diseases, most commonly hyperthyroidism. Although its genetic and epigenetic alterations do not directly lead to carcinogenesis, it has a crucial role in tumor growth, which is initiated by several oncogenes. This article will provide a brief review of TSHR and related diseases.

  18. Heterogeneity of protein hormones

    Energy Technology Data Exchange (ETDEWEB)

    Rosselin, G; Bataille, D; Laburthe, M; Duran-Garcia, S [Institut National de la Sante et de la Recherche Medicale (INSERM), Hopital Saint-Antoine, 75 - Paris (France)

    1975-12-01

    Radioimmunoassay measures antigenic determinants of hormonal molecules in the plasmas and tissues. These estimations carried out after fractionation in biological fluids, have revealed several immunological forms of the same hormone. The main problem is in the relationship of the various immunoreactive forms to the same hormonal sequence. The similar immunoreactive forms of high molecular weight usually have low biological activity and suggest the presence of prohormone; the suggestion of prohormonal nature depends on the chronology of the incorporation of labelled leucine and enzymatic transformation of prohormone with low biological into active hormone. The forms with high molecular weight and similar immunological activity may be of another nature. Thus, it has been shown that the biosynthetic nature of a compound such as big big insulin in the rat is doubtful owing to the absence of specific incorporation of labelled leucine into the immunoprecipitate of this fraction. The significance of low molecular weight form is still little known. An example of these forms is supplied by the existence of an alpha sub-unit of gonadotrophin present in the plasma of menopausal women. The interest of analytical methods by radio-receptor, simulation of cyclase activity in the identification of biological activity of immunoreactive forms, is discussed in relation to immunological forms ofenteroglucagon. An unusual aspect of the evolutive and adaptative character of hormonal heterogeneity is given by the gastro-intestinal hormones.

  19. Kinetics of thyroid hormones

    International Nuclear Information System (INIS)

    Inada, Mitsuo; Nishikawa, Mitsushige; Naito, Kimikazu; Ishii, Hitoshi; Tanaka, Kiyoshi

    1980-01-01

    Kinetics of thyroid hormones were outlined, and recent progress in metabolism of these hormones was also described. Recently, not only T 4 and T 3 but also rT 3 , 3,3'-T 2 , 3',5'-T 2 , and 3,5-T 2 can be measured by RIA. To clarify metabolic pathways of these hormones, metabolic clearance rate and production rate of these hormones were calculated. As single-compartment analysis was insufficient to clarify disappearance curves of thyroid hormones in blood such as T 3 and T 2 of which metabolic speed was so fast, multi-compartment analysis or non-compartment analysis were also performed. Thyroid hormones seemed to be measured more precisely by constant infusion method. At the first step of T 4 metabolism, T 3 was formed by 5'-monodeiodination of T 4 , and rT 3 was formed by 5-monodeiodination of T 4 . As metabolic pathways of T 3 and rT 3 , conversion of them to 3,3'-T 2 or to 3',5'-T 2 and 3,5-T 2 was supposed. This subject will be an interesting research theme in future. (Tsunoda, M.)

  20. Radioiodine uptake following iodine-131 therapy for Graves' disease: an early indicator of need for retreatment

    International Nuclear Information System (INIS)

    Carpentier, W.R.; Gilliland, P.F.; Piziak, V.K.; Petty, F.C.; McConnell, B.G.; Verdonk, C.A.; Ibarra, J.D.; Thompson, J.Q.

    1989-01-01

    Forty-five patients with Graves' disease were studied prospectively to determine if 24-hour I-131 uptake measurements alone or in combination with serum thyroid hormone levels at six weeks would determine the necessity for retreatment of the thyrotoxicosis. All patients with an I-131 uptake greater than 30% at six weeks required retreatment. No patient with an I-131 uptake of less than 15% required retreatment. Patients with uptakes between 15% and 30% were variable. An elevated free thyroxin index at 6 weeks is not helpful to determine which patients will remain thyrotoxic. Patients with a free thyroxin index within the normal range at six weeks can be predicted to be euthyroid by 12 weeks if their 24-hour I-131 uptake is between 15% and 30% and to be hypothyroid if their 24-hour I-131 uptake is below 15%. There was no difference between patient groups treated initially with antithyroid medication and those who were not

  1. Radioactive iodine uptake: deriving new message from an old test

    International Nuclear Information System (INIS)

    Gonzales, R.R.; Magboo, M.L.C.; San Luis, T.O.L.

    1993-01-01

    92 patients with elevated 4 hour RAIU were divided into two groups and analyzed. Group I consisted of 42 patients with rapid iodine trapping and organification (4 hour>24 hour). Group II consisted of 50 patients with progressively increasing RAIU (24 hour>4 hour). Analysis of the clinical manifestations of both groups by using the J. Crooks Scoring System showed that 37 patients (88%) in group I belonged to the toxic group while only 7 (14%) of patients in group II showed clear signs and symptoms of thyrotoxicosis. Independent 2-tailed t-test between the Crooks score of both groups showed significant difference (t=8.42). The uptake pattern of both groups showed significant differences in their uptake levels at p value<0.001. All of the patients in group I received antithyroid regimen while in group II, 26 patients (56%) were given thyroid hormone preparations and only 16 (32%) patients received anti-thyroid drugs. In the final analysis, patterns wherein the 4 hour uptake is higher than the 24 hour uptake are highly associated with hyperthyroidism. Those with sustained elevations of the 4 hour and the 24 hour RAIU should merit good correlation between the clinical and thyroid hormone level before initiating any treatment regimen. (author). 8 refs.; 8 tabs

  2. [7α-18F]fluoro-17α-methyl-5α-dihydrotestosterone: a ligand for androgen receptor-mediated imaging of prostate cancer

    International Nuclear Information System (INIS)

    Garg, Pradeep K.; Labaree, David C.; Hoyte, Robert M.; Hochberg, Richard B.

    2001-01-01

    We have synthesized a 18 F-labeled androgen, [7α- 18 F]fluoro-17α-methyl-5α-dihydrotestosterone, in a no-carrier-added radiosynthesis by exchange of 18 F- (tetrabutylammonium fluoride) with the 7β-tosyloxy of 17α-methyl-5α-dihydrotestosterone. The nonradioactive steroid binds with high affinity and specificity to the androgen receptor and binds poorly, if at all, to other steroid receptors and plasma sex hormone binding globulin. The 7α- 18 F-androgen concentrates markedly in the prostate of rats by an androgen receptor-dependent mechanism. It is likely that [7α- 18 F]fluoro-17α-methyl-5α-dihydrotestosterone will be an excellent positron emission tomography imaging agent for prostate cancer

  3. Investigations of the mechanism of vitamin E removal from blood and the effect of NO2 on the pulmonary uptake of vitamin E

    International Nuclear Information System (INIS)

    Gardner, H.K.

    1987-01-01

    To examine the effect of NO 2 on vitamin E uptake by lung, we first investigated the mechanism of removal of vitamin E from blood. To accomplish this, a method for labeling serum with tritiated vitamin E was developed. Two other lipids, whose uptake is better understood, were also studied, and compared with vitamin E. Tritiated triacylglycerol was used to monitor lipoprotein lipase-mediated uptake, while tritiated cholesterol was used to monitor LDL receptor-mediated uptake. Blood curves derived from untreated, adult, male, Long-Evans rats indicated that all three lipids were removed biexponentially. The half-life for the Rapid component was 2.5-3.7 minutes for all lipids. The slower curve had half-lives of 42.3 minutes for triacylglycerol, 990.0 minutes for cholesterol, and 288.8 minutes for vitamin E. Biological screening of labeled serum demonstrated that the faster process was not simply the removal of lipoproteins damaged by the labeling process. Hepatectomy affected the rate of neither triacylglycerol nor cholesterol removal, but did slow vitamin E uptake, suggesting a distinct role for liver in vitamin E extraction

  4. Cellular uptake of exogenous calcineurin B is dependent on TLR4/MD2/CD14 complexes, and CnB is an endogenous ligand of TLR4.

    Science.gov (United States)

    Yang, Jinju; Qin, Nannan; Zhang, Hongwei; Yang, Rui; Xiang, Benqiong; Wei, Qun

    2016-04-19

    Our previous research showed that recombinant calcineurin B (rhCnB) stimulates cytokine secretion by immune cells, probably through TLR4. Exogenous CnB can be incorporated into many different tumour cells in vitro, but the mode of uptake and receptors required remain unknown. Here, we report that exogenous CnB is taken up by cells in a time- and concentration-dependent manner via clathrin-dependent receptor-mediated internalization. Our findings further confirm that uptake is mediated by the TLR4/MD2 complex together with the co-receptor CD14. The MST results revealed a high affinity between CnB and the TLR4 receptor complex. No binding was detected between CnB and LPS. CnB inhibited the uptake of LPS, and LPS also inhibited the uptake of CnB. These results indicate that the uptake of exogenous CnB did not occur through LPS and that CnB was not a chaperone of LPS. Thus, we conclude that TLR4 receptor complexes were required for the recognition and internalization of exogenous CnB. CnB could be a potential endogenous ligand of TLR4 and function as an agonist of TLR4. These properties of CnB support its potential for development as an anti-cancer drug.

  5. Biochemical endpoints of glucocorticoid hormone action

    Energy Technology Data Exchange (ETDEWEB)

    Young, D.A.; Nicholson, M.L.; Guyette, W.A.; Giddings, S.J.; Mendelsohn, S.L.; Nordeen, S.K.; Lyons, R.T.

    1978-01-01

    Both the rapidly evolving metabolic effects of glucocorticoids and the more slowly developing lethal actions appear to be initiated via the synthesis of new mRNAs and proteins. The chronic suppression of cell growth may be the consequence of suppression of overall rates of protein synthesis (and probably RNA and DNA synthesis as well) that in turn may represent the cellular response to the small changes in ratios of adenine nucleotides that result from the suppression of oxidative ATP production. The inhibition of glucose transport may also play a role here to prevent a compensatory increase in glycolytic ATP production. Some other hormone actions, the decrease in the ability of cells to concentrate AIB and the increase in nuclear fragility are unrelated to, and evolve separately from, the hormonal inhibitions on energy production. Cell killing is not the result of suppression of protein synthesis, nor of hormone-induced increases in calcium uptake. While the mechanisms are unknown, the increase in nuclear fragility appears to be the earliest measure of their operation. In tumor cells resistance to lethal actions of glucocorticoids may emerge via the selection of cells with hardier membranes, that are better able to withstand the intracellular destructive events set in motion by high levels of glucocorticoids.

  6. Hormonal control of euryhalinity

    Science.gov (United States)

    Takei, Yoshio; McCormick, Stephen D.; McCormick, Stephen D.; Farrell, Anthony Peter; Brauner, Colin J.

    2013-01-01

    Hormones play a critical role in maintaining body fluid balance in euryhaline fishes during changes in environmental salinity. The neuroendocrine axis senses osmotic and ionic changes, then signals and coordinates tissue-specific responses to regulate water and ion fluxes. Rapid-acting hormones, e.g. angiotensins, cope with immediate challenges by controlling drinking rate and the activity of ion transporters in the gill, gut, and kidney. Slow-acting hormones, e.g. prolactin and growth hormone/insulin-like growth factor-1, reorganize the body for long-term acclimation by altering the abundance of ion transporters and through cell proliferation and differentiation of ionocytes and other osmoregulatory cells. Euryhaline species exist in all groups of fish, including cyclostomes, and cartilaginous and teleost fishes. The diverse strategies for responding to changes in salinity have led to differential regulation and tissue-specific effects of hormones. Combining traditional physiological approaches with genomic, transcriptomic, and proteomic analyses will elucidate the patterns and diversity of the endocrine control of euryhalinity.

  7. Headache And Hormones

    Directory of Open Access Journals (Sweden)

    Shukla Rakesh

    2002-01-01

    Full Text Available There are many reasons to suggest a link between headache and hormones. Migraine is three times common in women as compared to men after puberty, cyclic as well as non-cyclic fluctuations in sex hormone levels during the entire reproductive life span of a women are associated with changes in frequency or severity of migraine attack, abnormalities in the hypothalamus and pineal gland have been observed in cluster headache, oestrogens are useful in the treatment of menstrual migraine and the use of melatonin has been reported in various types of primary headaches. Headache associated with various endocrinological disorders may help us in a better understanding of the nociceptive mechanisms involved in headache disorders. Prospective studies using headache diaries to record the attacks of headache and menstrual cycle have clarified some of the myths associated with menstrual migraine. Although no change in the absolute levels of sex hormones have been reported, oestrogen withdrawal is the most likely trigger of the attacks. Prostaglandins, melatonin, opioid and serotonergic mechanisms may also have a role in the pathogenesis of menstrual migraine. Guidelines have been published by the IHS recently regarding the use of oral contraceptives by women with migraine and the risk of ischaemic strokes in migraineurs on hormone replacement therapy. The present review includes menstrual migraine, pregnancy and migraine, oral contraceptives and migraine, menopause and migraine as well as the hormonal changes in chronic migraine.

  8. [Hormones and hair growth].

    Science.gov (United States)

    Trüeb, R M

    2010-06-01

    With respect to the relationship between hormones and hair growth, the role of androgens for androgenetic alopecia (AGA) and hirsutism is best acknowledged. Accordingly, therapeutic strategies that intervene in androgen metabolism have been successfully developed for treatment of these conditions. Clinical observations of hair conditions involving hormones beyond the androgen horizon have determined their role in regulation of hair growth: estrogens, prolactin, thyroid hormone, cortisone, growth hormone (GH), and melatonin. Primary GH resistance is characterized by thin hair, while acromegaly may cause hypertrichosis. Hyperprolactinemia may cause hair loss and hirsutism. Partial synchronization of the hair cycle in anagen during late pregnancy points to an estrogen effect, while aromatase inhibitors cause hair loss. Hair loss in a causal relationship to thyroid disorders is well documented. In contrast to AGA, senescent alopecia affects the hair in a diffuse manner. The question arises, whether the hypothesis that a causal relationship exists between the age-related reduction of circulating hormones and organ function also applies to hair and the aging of hair.

  9. Dissecting Bacterial Cell Wall Entry and Signaling in Eukaryotic Cells: an Actin-Dependent Pathway Parallels Platelet-Activating Factor Receptor-Mediated Endocytosis.

    Science.gov (United States)

    Loh, Lip Nam; Gao, Geli; Tuomanen, Elaine I

    2017-01-03

    The Gram-positive bacterial cell wall (CW) peptidoglycan-teichoic acid complex is released into the host environment during bacterial metabolism or death. It is a highly inflammatory Toll-like receptor 2 (TLR2) ligand, and previous in vivo studies have demonstrated its ability to recapitulate pathological features of pneumonia and meningitis. We report that an actin-dependent pathway is involved in the internalization of the CW by epithelial and endothelial cells, in addition to the previously described platelet-activating factor receptor (PAFr)-dependent uptake pathway. Unlike the PAFr-dependent pathway, which is mediated by clathrin and dynamin and does not lead to signaling, the alternative pathway is sensitive to 5-(N-ethyl-N-isopropyl) amiloride (EIPA) and engenders Rac1, Cdc42, and phosphatidylinositol 3-kinase (PI3K) signaling. Upon internalization by this macropinocytosis-like pathway, CW is trafficked to lysosomes. Intracellular CW trafficking is more complex than previously recognized and suggests multiple points of interaction with and without innate immune signaling. Streptococcus pneumoniae is a major human pathogen infecting the respiratory tract and brain. It is an established model organism for understanding how infection injures the host. During infection or bacterial growth, bacteria shed their cell wall (CW) into the host environment and trigger inflammation. A previous study has shown that CW enters and crosses cell barriers by interacting with a receptor on the surfaces of host cells, termed platelet-activating factor receptor (PAFr). In the present study, by using cells that are depleted of PAFr, we identified a second pathway with features of macropinocytosis, which is a receptor-independent fluid uptake mechanism by cells. Each pathway contributes approximately the same amount of cell wall trafficking, but the PAFr pathway is silent, while the new pathway appears to contribute to the host inflammatory response to CW insult. Copyright © 2017

  10. Incidence and characteristics of uterine leiomyomas with FDG uptake

    International Nuclear Information System (INIS)

    Nishizawa, Sadahiko; Inubushi, Masayuki; Kido, Aki; Miyagawa, Masao; Inoue, Takeshi; Shinohara, Katsura; Kajihara, Makoto

    2008-01-01

    Uterine leiomyomas sometimes show focal 18 F-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET) images that may result in a false-positive diagnosis for malignant lesions. This study was conducted to investigate the incidence and characteristics of uterine leiomyomas that showed FDG uptake. We reviewed FDG-PET and pelvic magnetic resonance (MR) images of 477 pre-menopausal (pre-MP, age 42.1±7.3 years) and 880 post-MP (age 59.9±6.8 years) healthy women who underwent these tests as parts of cancer screening. Of 1357, 323 underwent annual cancer screening four times, 97 did three times, 191 did twice, and the rest were screened once. Focal FDG uptake (maximal standardized uptake value >3.0) in the pelvis was localized and characterized on co-registered PET/MR images. Uterine leiomyomas were found in 164 pre-MP and 338 post-MP women. FDG uptake was observed in 18 leiomyomas of 17 of the 164 (10.4%) pre-MP women and in 4 leiomyomas of 4 of the 338 (1.2%) post-MP women. The incidence was significantly higher in pre-MP women than in post-MP women (chi-square, P<0.001). Of the 22, 13 showed signal intensity equal to or higher than that of the myometrium on T2-weighted MR images, which suggested abundant cellularity, whereas the majority of leiomyomas without FDG uptake showed low signal intensity. Of the 13 women, 12 examined more than twice showed substantial changes in the level of FDG uptake in leiomyomas each year with FDG uptake disappearing or newly appearing. These changes were observed frequently in relation with menopause or menstrual phases. Leiomyomas with focal FDG uptake were seen in both pre- and post-MP women with a higher incidence in pre-MP women. Abundant cellularity and hormonal dependency may explain a part of the mechanisms of FDG uptake in leiomyomas. It is important to know that the level of FDG uptake in leiomyomas can change and newly appearing FDG uptake does not necessarily mean malignant transformation. (author)

  11. Stress and hormones

    Directory of Open Access Journals (Sweden)

    Salam Ranabir

    2011-01-01

    Full Text Available In the modern environment one is exposed to various stressful conditions. Stress can lead to changes in the serum level of many hormones including glucocorticoids, catecholamines, growth hormone and prolactin. Some of these changes are necessary for the fight or flight response to protect oneself. Some of these stressful responses can lead to endocrine disorders like Graves′ disease, gonadal dysfunction, psychosexual dwarfism and obesity. Stress can also alter the clinical status of many preexisting endocrine disorders such as precipitation of adrenal crisis and thyroid storm.

  12. Role of /sup 99/mTc pertechnetate uptake in the evaluation of thyroid function

    Energy Technology Data Exchange (ETDEWEB)

    Sucupira, M.S.; Camargo, E.E.; Nickoloff, E.L.; Alderson, P.O.; Wagner, H.N. Jr.

    1983-01-01

    To investigate the usefulness of the 20 min /sup 99/mTc-pertechnetate uptake test, the records of 246 consecutive patients were reviewed. Of these, 192 patients (151 females, 41 males; 10 weeks to 78 years) had at least one year clinical follow-up or a confirmed diagnosis by biopsy or surgery and were included in our study. In these patients, the /sup 99/mTc pertechnetate uptake and hormonal values (T3 resin uptake, T4 RIA, T-index) were obtained. These results were then compared to the clinical diagnosis at the time of the uptake and one year later. All patients received an i.v. injection of 5 mCi of /sup 99/mTc pertechnetate. Imaging was performed using a pinhole collimator and a scintillation camera interfaced to a computer. Regions of interest for the thyroid and the background were used to calculate the 20 min /sup 99/mTc pertechnetate uptake as a percentage of the injected dose. /sup 99/mTc uptake and hormonal values were confirmatory in 158 patients (82.3%): 138 were euthyroid, 18 were hyperthyroid and 2 were hypothyroid. In 29 other patients (15.1%) the pertechnetate uptake provided useful additional information and helped to identify Hashimoto's thyroiditis (8 patients); thyroid suppression by exogenous iodide, steroids or T4 (7 patients); overtreated hyperthyroidism (1 patient); persistent hyperthyroidism (5 patients); different stages of Grave's disease (4 patients); and toxic nodular goiter (4 patients). The /sup 99/mTc uptake was misleading in 5 euthyroid patients (2.6%). We have found the /sup 99/mTc pertechnetate uptake a useful adjunct to measurement of hormonal levels in patients with suspected thyroid disease.

  13. Ovarian hormones and obesity.

    Science.gov (United States)

    Leeners, Brigitte; Geary, Nori; Tobler, Philippe N; Asarian, Lori

    2017-05-01

    Obesity is caused by an imbalance between energy intake, i.e. eating and energy expenditure (EE). Severe obesity is more prevalent in women than men worldwide, and obesity pathophysiology and the resultant obesity-related disease risks differ in women and men. The underlying mechanisms are largely unknown. Pre-clinical and clinical research indicate that ovarian hormones may play a major role. We systematically reviewed the clinical and pre-clinical literature on the effects of ovarian hormones on the physiology of adipose tissue (AT) and the regulation of AT mass by energy intake and EE. Articles in English indexed in PubMed through January 2016 were searched using keywords related to: (i) reproductive hormones, (ii) weight regulation and (iii) central nervous system. We sought to identify emerging research foci with clinical translational potential rather than to provide a comprehensive review. We find that estrogens play a leading role in the causes and consequences of female obesity. With respect to adiposity, estrogens synergize with AT genes to increase gluteofemoral subcutaneous AT mass and decrease central AT mass in reproductive-age women, which leads to protective cardiometabolic effects. Loss of estrogens after menopause, independent of aging, increases total AT mass and decreases lean body mass, so that there is little net effect on body weight. Menopause also partially reverses women's protective AT distribution. These effects can be counteracted by estrogen treatment. With respect to eating, increasing estrogen levels progressively decrease eating during the follicular and peri-ovulatory phases of the menstrual cycle. Progestin levels are associated with eating during the luteal phase, but there does not appear to be a causal relationship. Progestins may increase binge eating and eating stimulated by negative emotional states during the luteal phase. Pre-clinical research indicates that one mechanism for the pre-ovulatory decrease in eating is a

  14. Calcidiol and vitamin D binding protein uptake by LLC-PK1 cells

    International Nuclear Information System (INIS)

    Keenan, M.J.; Holmes, R.P.

    1986-01-01

    The process by which target cells take up vitamin D and its metabolites is not known. The authors studied the uptake of both 3 H-calcidiol and 125 I-Vitamin D Binding Protein (DBP) by LLC-PK 1 cells. Uptake was directly related to their extracellular concentrations. In the presence of 55 serum in the growth media cells previously incubated with 10 nM calcitriol for 4 hr had a greater uptake of calcidiol than those cells not incubated with calcitriol. This effect of calcitriol on calcidiol uptake was absent when cells were grown in hormone-supplemented, serum-free media, despite these cells having a cytosolic calcitriol receptor. Equal uptake of calcidiol occurred when DBP was absent and when DBP was present in a one to one molar ratio to calcidiol. With a 1:1 ratio of DBP to calcidiol and a measured K/sub D/ of 2 x 10 -8 M, the uptake of calcidiol could not be accounted for by uptake of the free ligand alone. A large excess of DBP (100:1) in relation to calcidiol suppressed uptake of calcidiol by approx. 90%. The authors have not been able to identify a saturable, specific uptake of either calcidiol or DBP despite DBP appearing to facilitate calcidiol uptake

  15. Exosomes: Mechanisms of Uptake

    Directory of Open Access Journals (Sweden)

    Kelly J. McKelvey

    2015-07-01

    Full Text Available Exosomes are 30–100 nm microvesicles which contain complex cellular signals of RNA, protein and lipids. Because of this, exosomes are implicated as having limitless therapeutic potential for the treatment of cancer, pregnancy complications, infections, and autoimmune diseases. To date we know a considerable amount about exosome biogenesis and secretion, but there is a paucity of data regarding the uptake of exosomes by immune and non-immune cell types (e.g., cancer cells and the internal signalling pathways by which these exosomes elicit a cellular response. Answering these questions is of paramount importance.

  16. Exosomes: Mechanisms of Uptake

    Directory of Open Access Journals (Sweden)

    Kelly J. McKelvey

    2015-07-01

    Full Text Available Exosomes are 30–100 nm microvesicles which contain complex cellular signals of RNA, protein and lipids. Because of this, exosomes are implicated as having limitless therapeutic potential for the treatment of cancer, pregnancy complications, infections, and autoimmune diseases. To date we know a considerable amount about exosome biogenesis and secretion, but there is a paucity of data regarding the uptake of exosomes by immune and non- immune cell types (e.g., cancer cells and the internal signalling pathways by which these exosomes elicit a cellular response. Answering these questions is of para‐ mount importance.

  17. Role of G3BP1 in glucocorticoid receptor-mediated microRNA-15b and microRNA-23a biogenesis in endothelial cells

    KAUST Repository

    Kwok, Hoi-Hin

    2017-05-18

    MicroRNAs (miRNAs) are a family of non-coding RNAs that play crucial roles in regulating various normal cellular responses. Recent studies revealed that the canonical miRNA biogenesis pathway is subject to sophisticated regulation. Hormonal control of miRNA biogenesis by androgen and estrogen has been demonstrated, but the direct effects of the glucocorticoid receptor (GR) on miRNA biogenesis are unknown. This study revealed the role of GR in miRNA maturation. We showed that two GR agonists, dexamethasone and ginsenoside-Rg1 rapidly suppressed the expression of mature miR-15b, miR-23a, and miR-214 in human endothelial cells. RNA pulldown coupled with proteomic analysis identified GTPase-activating protein (SH3 domain) binding protein 1 (G3BP1) as one of the RNA-binding proteins mediating GR-regulated miRNA maturation. Activated GR induced phosphorylation of v-AKT Murine Thymoma Viral Oncogene Homologue (AKT) kinase, which in turn phosphorylated and promoted nuclear translocation of G3BP1. The nuclear G3BP1 bound to the G3BP1 consensus sequence located on primary miR-15b~16-2 and miR-23a~27a~24-2 to inhibit their maturation. The findings from this study have advanced our understanding of the non-genomic effects of GR in the vascular system.

  18. The GLP-1 Receptor Agonist Exendin-4 and Diazepam Differentially Regulate GABAA Receptor-Mediated Tonic Currents in Rat Hippocampal CA3 Pyramidal Neurons.

    Directory of Open Access Journals (Sweden)

    Sergiy V Korol

    Full Text Available Glucagon-like peptide-1 (GLP-1 is a metabolic hormone that is secreted in a glucose-dependent manner and enhances insulin secretion. GLP-1 receptors are also found in the brain where their signalling affects neuronal activity. We have previously shown that the GLP-1 receptor agonists, GLP-1 and exendin-4 enhanced GABA-activated synaptic and tonic currents in rat hippocampal CA3 pyramidal neurons. The hippocampus is the centre for memory and learning and is important for cognition. Here we examined if exendin-4 similarly enhanced the GABA-activated currents in the presence of the benzodiazepine diazepam. In whole-cell recordings in rat brain slices, diazepam (1 μM, an allosteric positive modulator of GABAA receptors, alone enhanced the spontaneous inhibitory postsynaptic current (sIPSC amplitude and frequency by a factor of 1.3 and 1.6, respectively, and doubled the tonic GABAA current normally recorded in the CA3 pyramidal cells. Importantly, in the presence of exendin-4 (10 nM plus diazepam (1 μM, only the tonic but not the sIPSC currents transiently increased as compared to currents recorded in the presence of diazepam alone. The results suggest that exendin-4 potentiates a subpopulation of extrasynaptic GABAA receptors in the CA3 pyramidal neurons.

  19. HR38, an ortholog of NR4A family nuclear receptors, mediates 20-hydroxyecdysone regulation of carbohydrate metabolism during mosquito reproduction.

    Science.gov (United States)

    Dong, Dujuan; Zhang, Yang; Smykal, Vlastimil; Ling, Lin; Raikhel, Alexander S

    2018-05-01

    The Aedes aegypti mosquito is the principal vector for many dangerous human viral diseases. Carbohydrate metabolism (CM) is essential for supplying the energy necessary for host seeking, blood digestion and rapid egg development of this vector insect. The steroid hormone 20-hydroxyecdysone (20E) and the ecdysone receptor (EcR) are important regulators of CM, coordinating it with female reproductive events. We report here that the NR4A nuclear receptor AHR38 plays a critical role in mediating these actions of 20E and EcR. AHR38 RNA interference (RNAi) depletion in female mosquitoes blocked the transcriptional activation of CM genes encoding phosphoglucomutase (PGM) and trehalose-6-phophate synthase (TPS); it caused an increase of glycogen accumulation and a decrease of the circulating sugar trehalose. This treatment also resulted in a dramatic reduction in fecundity. Considering that these phenotypes resulting from AHR38 RNAi depletion are similar to those of EcR RNAi, we investigated a possible connection between these transcription factors in CM regulation. EcR RNAi inhibits the AHR38 gene expression. Moreover, the 20E-induced EcR complex directly activates AHR38 by binding to the ecdysone response element (EcRE) in the upstream regulatory region of this gene. The present work has implicated AHR38 in the 20E-mediated control of CM and provided new insight into mechanisms of 20E regulation of metabolism during female mosquito reproduction. © 2018 Published by Elsevier Ltd.

  20. Subcellular localisation of BAG-1 and its regulation of vitamin D receptor-mediated transactivation and involucrin expression in oral keratinocytes: Implications for oral carcinogenesis

    International Nuclear Information System (INIS)

    Lee, San San; Crabb, Simon J.; Janghra, Nari; Carlberg, Carsten; Williams, Ann C.; Cutress, Ramsey I.; Packham, Graham; Hague, Angela

    2007-01-01

    In oral cancers, cytoplasmic BAG-1 overexpression is a marker of poor prognosis. BAG-1 regulates cellular growth, differentiation and survival through interactions with diverse proteins, including the vitamin D receptor (VDR), a key regulator of keratinocyte growth and differentiation. BAG-1 is expressed ubiquitously in human cells as three major isoforms of 50 kDa (BAG-1L), 46 kDa (BAG-1M) and 36 kDa (BAG-1S) from a single mRNA. In oral keratinocytes BAG-1L, but not BAG-1M and BAG-1S, enhanced VDR transactivation in response to 1α,25-dihydroxyvitamin D 3. BAG-1L was nucleoplasmic and nucleolar, whereas BAG-1S and BAG-1M were cytoplasmic and nucleoplasmic in localisation. Having identified the nucleolar localisation sequence in BAG-1L, we showed that mutation of this sequence did not prevent BAG-1L from potentiating VDR activity. BAG-1L also potentiated transactivation of known vitamin-D-responsive gene promoters, osteocalcin and 24-hydroxylase, and enhanced VDR-dependent transcription and protein expression of the keratinocyte differentiation marker, involucrin. These results demonstrate endogenous gene regulation by BAG-1L by potentiating nuclear hormone receptor function and suggest a role for BAG-1L in 24-hydroxylase regulation of vitamin D metabolism and the cellular response of oral keratinocytes to 1α,25-dihydroxyvitamin D 3 . By contrast to the cytoplasmic BAG-1 isoforms, BAG-1L may act to suppress tumorigenesis

  1. The CSF and arterial to internal jugular venous hormonal differences during exercise in humans

    DEFF Research Database (Denmark)

    Dalsgaard, M.K.; Ott, P.; Dela, F.

    2004-01-01

    Strenuous exercise increases the cerebral uptake of carbohydrate out of proportion to that of oxygen, but it is unknown whether such enhanced carbohydrate uptake is influenced by the marked endocrine response to exercise. During exhaustive exercise this study evaluated the a-v differences across...... the brain (a-v diff) of hormones that could influence its carbohydrate uptake (n= 9). In addition, neuroendocrine activity and a potential uptake of hormones via the cerebrospinal fluid (CSF) were assessed by lumbar puncture postexercise and at rest (n= 6). Exercise increased the arterial concentration......)(+) and its a-v diff, which increased from 1 (-12 to 5) to 17 (5-41) micromol l(-1) (P brain of interleukin (IL)-6, tumour necrosis factor (TNF-alpha), heatshock...

  2. Radioimmunoassay of steroid hormone

    International Nuclear Information System (INIS)

    Murakami, Tadashi

    1975-01-01

    Low acid pepsin treated gamma-globulin was applied to ammonium sulfate salting out method, which was a method to separate bound fraction from free one in radioimmunoassay of steroid hormone, and the effect of the separation and the standard curve were examined. Pepsin treated gamma-globulin was prepared in pH 1.5 to 5.5 and then the pepsin was completely removed. It had an effect to accelerate the precipitation in radioimmunoassay of steroid hormone labelled with 3 H. The effect of pepsin treated gamma-globulin to adhere free steroid hormone and to slat out bound one was compared with that of human gamma-globulin. Pepsin treated gamma-globulin, which was water soluble, could easier reach its optimal concentration, and the separation effect was better than human gamma-globulin. The standard curve of it was steeper, particularly in a small dose, and the reproducibility was also better. It could be applied not only to aldosterone and DOC, but also to the steroid hormones, such as progesterone and DHEA, and it seemed suitable for routine measurement method. (Kanao, N.)

  3. Hormones and social preferences

    NARCIS (Netherlands)

    Buser, T.

    2011-01-01

    We examine whether social preferences are determined by hormones. We do this by investigating whether markers for the strength of prenatal testosterone exposure (finger length ratios) and current exposure to progesterone and oxytocin (the menstrual cycle) are correlated with choices in social

  4. Thyroid hormone replacement therapy

    NARCIS (Netherlands)

    Wiersinga, W. M.

    2001-01-01

    Thyroid hormone replacement has been used for more than 100 years in the treatment of hypothyroidism, and there is no doubt about its overall efficacy. Desiccated thyroid contains both thyroxine (T(4)) and triiodothyronine (T(3)); serum T(3) frequently rises to supranormal values in the absorption

  5. Hormones and postpartum cardiomyopathy.

    NARCIS (Netherlands)

    Clapp, C.; Thebault, S.C.; Martinez de la Escalera, G.M.

    2007-01-01

    Prolactin, a hormone fundamental for lactation, was recently shown to mediate postpartum cardiomyopathy, a life-threatening disease in late-term and lactating mothers. The detrimental effect of prolactin results from myocardial upregulation of cathepsin-D, which in turn cleaves prolactin to a 16 kDa

  6. Inappropriate Antidiuretic Hormone Secretion

    African Journals Online (AJOL)

    1974-06-08

    Jun 8, 1974 ... with Addison's disease, diarrhoea or salt-losing nephritis. (asymptomatic hyponatraemia).~ Schwartz et al.3 stud;ed two patients with anaplastic bronchus carcinoma and hyponatraemia in 1957, and they suggested that there was an inappropriate secretion of antidiuretic hormone (ADH). It is now well ...

  7. Radioimmunoassay of protein hormones

    International Nuclear Information System (INIS)

    Talas, M.; Fingerova, H.

    1976-01-01

    A survey is presented of the history of RIA methods for FSH, LH, HCG, HPL and prolactin determinations with special regard to the double antibody method in a kinetic system. Problems are shown in 125 I-labelling protein hormones in preparing own antisera. (L.O.)

  8. SHBG (Sex Hormone Binding Globulin)

    Science.gov (United States)

    ... Links Patient Resources For Health Professionals Subscribe Search Sex Hormone Binding Globulin (SHBG) Send Us Your Feedback ... As Testosterone-estrogen Binding Globulin TeBG Formal Name Sex Hormone Binding Globulin This article was last reviewed ...

  9. Gastrointestinal hormones and their targets

    DEFF Research Database (Denmark)

    Rehfeld, Jens F.

    2014-01-01

    Gastrointestinal hormones are peptides released from endocrine cells and neurons in the digestive tract. More than 30 hormone genes are currently known to be expressed in the gastrointestinal tract, which makes the gut the largest hormone producing organ in the body. Modern biology makes...... it feasible to conceive the hormones under five headings: The structural homology groups a majority of the hormones into nine families, each of which is assumed to originate from one ancestral gene. The individual hormone gene often has multiple phenotypes due to alternative splicing, tandem organization......, or differentiated maturation of the prohormone. By a combination of these mechanisms, more than 100 different hormonally active peptides are released from the gut. Gut hormone genes are also widely expressed in cells outside the gut, some only in extraintestinal endocrine cells and neurons but others also in other...

  10. Luteinizing hormone (LH) blood test

    Science.gov (United States)

    ICSH - blood test; Luteinizing hormone - blood test; Interstitial cell stimulating hormone - blood test ... to temporarily stop medicines that may affect the test results. Be sure to tell your provider about ...

  11. Hormone Therapy for Breast Cancer

    Science.gov (United States)

    ... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... sensitive breast cancer cells contain proteins called hormone receptors that become activated when hormones bind to them. ...

  12. Thyroid Uptake Measurement System

    International Nuclear Information System (INIS)

    Nguyen Duc Tuan; Nguyen Thi Bao My; Nguyen Van Sy

    2007-01-01

    The NED-UP.M7 is a complete thyroid uptake and analysis system specifically designed for nuclear medicine. Capable of performing a full range of studies this system provides fast, accurate results for Uptake Studies. The heart of the NED-UP.M7 is a microprocessor-controlled 2048 channel Compact Multi-Channel Analyzer, coupled to a 2 inch x 2 inch NaI(Tl) detector with a USB personal computer interface. The system offers simple, straight-forward operation using pre-programmed isotopes, and menudriven prompts to guide the user step by step through each procedure. The pre-programmed radionuclides include I-123, I-125, I-131, Tc-99m and Cs-137. The user-defined radionuclides also allow for isotope identification while the printer provides hard copy printouts for patient and department record keeping. The included software program running on PC (Windows XP-based) is a user friendly program with menudriven and graphic interface for easy controlling the system and managing measurement results of patient on Excel standard form. (author)

  13. Ghrelin receptors mediate ghrelin-induced excitation of agouti-related protein/neuropeptide Y but not pro-opiomelanocortin neurons.

    Science.gov (United States)

    Chen, Shao-Rui; Chen, Hong; Zhou, Jing-Jing; Pradhan, Geetali; Sun, Yuxiang; Pan, Hui-Lin; Li, De-Pei

    2017-08-01

    Ghrelin increases food intake and body weight by stimulating orexigenic agouti-related protein (AgRP)/neuropeptide Y (NPY) neurons and inhibiting anorexic pro-opiomelanocortin (POMC) neurons in the hypothalamus. Growth hormone secretagogue receptor (Ghsr) mediates the effect of ghrelin on feeding behavior and energy homeostasis. However, the role of Ghsr in the ghrelin effect on these two populations of neurons is unclear. We hypothesized that Ghsr mediates the effect of ghrelin on AgRP and POMC neurons. In this study, we determined whether Ghsr similarly mediates the effects of ghrelin on AgRP/NPY and POMC neurons using cell type-specific Ghsr-knockout mice. Perforated whole-cell recordings were performed on green fluorescent protein-tagged AgRP/NPY and POMC neurons in the arcuate nucleus in hypothalamic slices. In Ghsr +/+ mice, ghrelin (100 nM) significantly increased the firing activity of AgRP/NPY neurons but inhibited the firing activity of POMC neurons. In Ghsr -/- mice, the excitatory effect of ghrelin on AgRP/NPY neurons was abolished. Ablation of Ghsr also eliminated ghrelin-induced increases in the frequency of GABAergic inhibitory postsynaptic currents of POMC neurons. Strikingly, ablation of Ghsr converted the ghrelin effect on POMC neurons from inhibition to excitation. Des-acylated ghrelin had no such effect on POMC neurons in Ghsr -/- mice. In both Ghsr +/+ and Ghsr -/- mice, blocking GABA A receptors with gabazine increased the basal firing activity of POMC neurons, and ghrelin further increased the firing activity of POMC neurons in the presence of gabazine. Our findings provide unequivocal evidence that Ghsr is essential for ghrelin-induced excitation of AgRP/NPY neurons. However, ghrelin excites POMC neurons through an unidentified mechanism that is distinct from conventional Ghsr. © 2017 International Society for Neurochemistry.

  14. High-mobility group (HMG) protein HMG-1 and TATA-binding protein-associated factor TAF(II)30 affect estrogen receptor-mediated transcriptional activation.

    Science.gov (United States)

    Verrier, C S; Roodi, N; Yee, C J; Bailey, L R; Jensen, R A; Bustin, M; Parl, F F

    1997-07-01

    The estrogen receptor (ER) belongs to a family of ligand-inducible nuclear receptors that exert their effects by binding to cis-acting DNA elements in the regulatory region of target genes. The detailed mechanisms by which ER interacts with the estrogen response element (ERE) and affects transcription still remain to be elucidated. To study the ER-ERE interaction and transcription initiation, we employed purified recombinant ER expressed in both the baculovirus-Sf9 and his-tagged bacterial systems. The effect of high-mobility group (HMG) protein HMG-1 and purified recombinant TATA-binding protein-associated factor TAF(II)30 on ER-ERE binding and transcription initiation were assessed by electrophoretic mobility shift assay and in vitro transcription from an ERE-containing template (pERE2LovTATA), respectively. We find that purified, recombinant ER fails to bind to ERE in spite of high ligand-binding activity and electrophoretic and immunological properties identical to ER in MCF-7 breast cancer cells. HMG-1 interacts with ER and promotes ER-ERE binding in a concentration- and time-dependent manner. The effectiveness of HMG-1 to stimulate ER-ERE binding in the electrophoretic mobility shift assay depends on the sequence flanking the ERE consensus as well as the position of the latter in the oligonucleotide. We find that TAF(II)30 has no effect on ER-ERE binding either alone or in combination with ER and HMG-1. Although HMG-1 promotes ER-ERE binding, it fails to stimulate transcription initiation either in the presence or absence of hormone. In contrast, TAF(II)30, while not affecting ER-ERE binding, stimulates transcription initiation 20-fold in the presence of HMG-1. These results indicate that HMG-1 and TAF(II)30 act in sequence, the former acting to promote ER-ERE binding followed by the latter to stimulate transcription initiation.

  15. Radioimmunoassay of polypeptide hormones and enzymes

    International Nuclear Information System (INIS)

    Felber, J.P.

    1974-01-01

    General principles of radioimmunoassay are reviewed. Detailed procedures are reviewed for the following hormones: insulin, pituitary hormones, gonadotropins, parathyroid hormone, ACTH, glucagon, gastrin, and peptide hormones. Radioimmunoassay of enzymes is also discussed. (U.S.)

  16. Disruption of Lipid Uptake in Astroglia Exacerbates Diet-Induced Obesity

    NARCIS (Netherlands)

    Gao, Yuanqing; Layritz, Clarita; Legutko, Beata; Eichmann, Thomas O.; Laperrousaz, Elise; Moullé, Valentine S.; Cruciani-Guglielmacci, Celine; Magnan, Christophe; Luquet, Serge; Woods, Stephen C.; Eckel, Robert H.; Yi, Chun-Xia; Garcia-Caceres, Cristina; Tschöp, Matthias H.

    2017-01-01

    Neuronal circuits in the brain help to control feeding behavior and systemic metabolism in response to afferent nutrient and hormonal signals. Although astrocytes have historically been assumed to have little relevance for such neuroendocrine control, we investigated whether lipid uptake via

  17. Propensity of red blood cells to undergo P2X7 receptor-mediated phosphatidylserine exposure does not alter during in vivo or ex vivo aging.

    Science.gov (United States)

    Sophocleous, Reece A; Mullany, Phillip R F; Winter, Kelly M; Marks, Denese C; Sluyter, Ronald

    2015-08-01

    Phosphatidylserine (PS) exposure facilitates the removal of red blood cells (RBCs) from the circulation, potentially contributing to the loss of stored RBCs after transfusion, as well as senescent RBCs. Activation of the P2X7 receptor by extracellular adenosine 5'-triphosphate (ATP) can induce PS exposure on freshly isolated human RBCs, but whether this process occurs in stored RBCs or changes during RBC aging is unknown. RBCs were processed and stored according to Australian blood banking guidelines. PS exposure was determined by annexin V binding and flow cytometry. Efficacy of P2X antagonists was assessed by flow cytometric measurements of ATP-induced ethidium+ uptake in RPMI 8226 cells. Osmotic fragility was assessed by lysis in hypotonic saline. RBCs were fractionated by discontinuous density centrifugation. ATP (1 mmol/L) induced PS exposure on RBCs stored for less than 1 week. This process was near-completely inhibited by the P2X7 antagonists A438079 and AZ10606120 and the P2X1/P2X7 antagonist MRS2159 but not the P2X1 antagonist NF499. ATP-induced PS exposure on RBCs was not dependent on K+, Na+, or Cl- fluxes. ATP did not alter the osmotic fragility of stored RBCs. ATP-induced PS exposure was similar between RBCs of different densities. ATP-induced PS exposure was also similar between RBCs stored for less than 1 week or for 6 weeks. The propensity of RBCs to undergo P2X7-mediated PS exposure does not alter during in vivo and ex vivo aging. Thus, P2X7 activation is unlikely to be involved in the removal of senescent RBCs or stored RBCs after transfusion. © 2015 AABB.

  18. Physiological FDG uptake in the ovaries after hysterectomy

    International Nuclear Information System (INIS)

    Nishizawa, Sadahiko; Inubushi, Masayuki; Ozawa, Fukujiro; Kido, Aki; Okada, Hiroyuki

    2007-01-01

    It is known that focal 18 F-fluorodeoxyglucose (FDG) uptake is physiologically seen in the ovaries and uterus of premenopausal women in correlation with the menstrual cycle, which may cause false-positive diagnoses on the images of FDG positron emission tomography (PET). The objective of this study was to clarify whether women of reproductive age after hysterectomy whose ovaries were preserved, also showed physiological ovarian FDG uptake. We reviewed 26 women after hysterectomy (age 51.1±5.0 years), who underwent annual cancer screening, including FDG-PET and pelvic magnetic resonance (MR) imaging, three times. Seven women (age 45.9±5.8 years, range 34-52 years) had at least one ovary, showing changes in its appearance including the size and number of follicles on MR images each year, which suggested that the ovary was functioning. Four of the seven women showed focal FDG uptake (standardized uptake value 4.2±1.1) that corresponded to the normal ovaries on five PET examinations. Another group of 19 women (age 53.1±3.1 years, range 47-59 years) who had small ovaries without changes on MR images each year did not show FDG uptake in the ovaries. Physiological FDG uptake observed in the ovaries of women of reproductive age even after hysterectomy is reasonably common. As it is not easy to determine the hormonal cycle in these women, it is essential to correlate focal FDG uptake in the pelvis with anatomical and morphological findings on MR images to avoid false-positive diagnoses. (author)

  19. Low density lipoprotein uptake by an endothelial-smooth muscle cell bilayer

    International Nuclear Information System (INIS)

    Alexander, J.J.; Miguel, R.; Graham, D.

    1991-01-01

    To study the interaction of endothelial and smooth muscle cells, and the means by which such interaction may affect lipid permeability of the arterial wall, cell bilayers were established by use of a transwell culture system. After confluent growth of both cell types had been achieved, iodine 125 bound to low-density lipoprotein (10 ng protein/ml) was added to the media of the upper well. After a 3-hour incubation period, the iodine 125-bound low-density lipoprotein content of the upper and lower media demonstrated an impedance to lipoprotein movement across the endothelial cell monolayer as compared to the bare porous polycarbonate filter of the transwell (p less than 10(-6)). The presence of smooth muscle cells in the bottom well significantly enhanced the permeability of the endothelial cell layer (p less than 10(-60)). This effect remained unchanged over a 9-day time course. Membrane binding and cellular uptake of low-density lipoprotein by endothelial cells was not altered by smooth muscle cells, indicating that this change in permeability could not be easily attributed to changes in receptor-mediated transport or transcytosis. Membrane binding (p less than 0.02) and cellular uptake (p less than 10(-6)) of low-density lipoprotein by smooth muscle cells in the bilayer, when adjusted for counts available in the smooth muscle cell media, were both reduced in the early incubation period as compared to isolated smooth muscle cells. The disproportionate reduction in uptake as compared to binding would suggest that this was not entirely a receptor-dependent process

  20. Effects of polyamine inhibitors on zinc uptake by COMMA-1D mammary epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Allen, J.C.; Haedrich, L.H. (North Carolina State Univ., Raleigh (United States))

    1991-03-15

    Zn uptake or transport is stimulated by glucocorticoids in many types of epithelial cells, including the COMMA-1D mouse mammary cell line. The current objective was to determine whether polyamines also mediate glucocorticoid stimulation of Zn-uptake. Initially, cells grown in lactogenic hormone supplemented-media had approximately 65% greater {sup 65}Zn-uptake over 24 h than cells in nonsupplemented growth media (GM). {sup 65}Zn-uptake from HM with 10{sup {minus}5}M methylglyoxal-bis(guanylhydrazone) (MGBG) (s-adenosyl-methionine decarboxylase inhibitor to block polyamine synthesis) added was less than from GM. Exogenous spermidine added to the MGBG-HM media increased {sup 65}Zn-uptake. However, up to 10mM difluoromethylornithine (DFMO), a more specific inhibitor of sperimidine synthesis, had no significant effect on 24-h {sup 65}Zn-uptake by cells in HM. In GM, DFMO caused a slight dose-dependent decrease in {sup 65}Zn-uptake over the range 10{sup {minus}6} to 5 {times} 10{sup 3}M. Also, with 8 h of incubation, DFMO tended to decrease {sup 65}Zn-uptake in HM-stimulated cells. These data cannot yet distinguish between the possibilities that DFMO is inactivated during the 24-h incubation or that the dramatic effects of MGBG on {sup 65}Zn-uptake in these mammary-derived cells is not related to its inhibition of polyamine synthesis. Because COMMA-1D cells alter Zn uptake in response to lactogenic hormones and MGBG, the model system is suitable for further studies of the mechanisms of zinc transport in epithelia.

  1. Sex Hormones and Tendon

    DEFF Research Database (Denmark)

    Hansen, Mette; Kjaer, Michael

    2016-01-01

    The risk of overuse and traumatic tendon and ligament injuries differ between women and men. Part of this gender difference in injury risk is probably explained by sex hormonal differences which are specifically distinct during the sexual maturation in the teenage years and during young adulthood....... The effects of the separate sex hormones are not fully elucidated. However, in women, the presence of estrogen in contrast to very low estrogen levels may be beneficial during regular loading of the tissue or during recovering after an injury, as estrogen can enhance tendon collagen synthesis rate. Yet...... has also been linked to a reduced responsiveness to relaxin. The present chapter will focus on sex difference in tendon injury risk, tendon morphology and tendon collagen turnover, but also on the specific effects of estrogen and androgens....

  2. Gut hormones and gastric bypass

    DEFF Research Database (Denmark)

    Holst, Jens J.

    2016-01-01

    Gut hormone secretion in response to nutrient ingestion appears to depend on membrane proteins expressed by the enteroendocrine cells. These include transporters (glucose and amino acid transporters), and, in this case, hormone secretion depends on metabolic and electrophysiological events elicited...... that determines hormone responses. It follows that operations that change intestinal exposure to and absorption of nutrients, such as gastric bypass operations, also change hormone secretion. This results in exaggerated increases in the secretion of particularly the distal small intestinal hormones, GLP-1, GLP-2......, oxyntomodulin, neurotensin and peptide YY (PYY). However, some proximal hormones also show changes probably reflecting that the distribution of these hormones is not restricted to the bypassed segments of the gut. Thus, cholecystokinin responses are increased, whereas gastric inhibitory polypeptide responses...

  3. Thyroid hormone radioimmunoassay

    International Nuclear Information System (INIS)

    Rodriguez, S.; Richmond, M.; Quesada, S.; Lahaman, S.; Ramirez, A.; Herrera, J.F.

    1988-01-01

    The International Atomic Energy Agency (AIEA) is carrying out the ARCAL VIII Program 'Thiroid Hormone Readioimmunoassay'. The Immunoassay Laboratory of INCIENSA is in charge of this program, with the participation of four National Hospital System laboratories, which carried out Thyroxine (T4). Triodothyroxine (T3) and Thyroid Stimulating Hormone (TSH) assays with NETRIA Reagents (North East Thames Region Immunoassay Unit). The variability was shown to be between 9-20 per cent for T4, 12-22 per cent for TSH and 22-36 per cent for T3. The study also evaluated the quality of a tracer (T3-l125 and T4 l125) produced at INCIENSA. In this case the intrassay variability was 8,4 per cent for T3 and 6,8 per cent for T4 in 32 determinations evaluated during 6 months. It was concluded that the T4 and TSH tests but not the T3 test are valid and reproducible when NETRIA Ragents are used. The tracer made at INCIENSA can be used up to 6 weeks after the radioiodination with l125. A successful thyroid-related hormones quality control was defined in Costa Rica by taking advantage of the support of a prestigious international agency, the IAEA. (author). 13 refs, 4 figs

  4. Radioiodine uptake measurements in thyroid

    International Nuclear Information System (INIS)

    Kadireshn, A.; Kapur, S.C.; Samuel, J.R.; Mahajan, M.K.

    1988-01-01

    Evaluation of thyroid function can be carried out by measuring the uptake of orally administered radioactive iodine. The results of the thyroid uptake measurements for the period 1982-1987 in Christian Medical College, Ludhiana are presented here. About 3000 patients were screened during the analysis period. (author)

  5. Aquaporins and root water uptake

    Science.gov (United States)

    Water is one of the most critical resources limiting plant growth and crop productivity, and root water uptake is an important aspect of plant physiology governing plant water use and stress tolerance. Pathways of root water uptake are complex and are affected by root structure and physiological res...

  6. Uptake of nuclides by plants

    International Nuclear Information System (INIS)

    Greger, Maria

    2004-04-01

    This review on plant uptake of elements has been prepared to demonstrate how plants take up different elements. The work discusses the nutrient elements, as well as the general uptake and translocation in plants, both via roots and by foliar absorption. Knowledge of the uptake by the various elements within the periodic system is then reviewed. The work also discusses transfer factors (TF) as well as difficulties using TF to understand the uptake by plants. The review also focuses on species differences. Knowledge necessary to understand and calculate plant influence on radionuclide recirculation in the environment is discussed, in which the plant uptake of a specific nuclide and the fate of that nuclide in the plant must be understood. Plants themselves determine the uptake, the soil/sediment determines the availability of the nuclides and the nuclides themselves can interact with each other, which also influences the uptake. Consequently, it is not possible to predict the nuclide uptake in plants by only analysing the nuclide concentration of the soil/substrate

  7. Uptake of nuclides by plants

    Energy Technology Data Exchange (ETDEWEB)

    Greger, Maria [Stockholm Univ. (Sweden). Dept. of Botany

    2004-04-01

    This review on plant uptake of elements has been prepared to demonstrate how plants take up different elements. The work discusses the nutrient elements, as well as the general uptake and translocation in plants, both via roots and by foliar absorption. Knowledge of the uptake by the various elements within the periodic system is then reviewed. The work also discusses transfer factors (TF) as well as difficulties using TF to understand the uptake by plants. The review also focuses on species differences. Knowledge necessary to understand and calculate plant influence on radionuclide recirculation in the environment is discussed, in which the plant uptake of a specific nuclide and the fate of that nuclide in the plant must be understood. Plants themselves determine the uptake, the soil/sediment determines the availability of the nuclides and the nuclides themselves can interact with each other, which also influences the uptake. Consequently, it is not possible to predict the nuclide uptake in plants by only analysing the nuclide concentration of the soil/substrate.

  8. Thyroid Hormones Are Transport Substrates and Transcriptional Regulators of Organic Anion Transporting Polypeptide 2B1.

    Science.gov (United States)

    Meyer Zu Schwabedissen, Henriette E; Ferreira, Celio; Schaefer, Anima M; Oufir, Mouhssin; Seibert, Isabell; Hamburger, Matthias; Tirona, Rommel G

    2018-07-01

    Levothyroxine replacement therapy forms the cornerstone of hypothyroidism management. Variability in levothyroxine oral absorption may contribute to the well-recognized large interpatient differences in required dose. Moreover, levothyroxine-drug pharmacokinetic interactions are thought to be caused by altered oral bioavailability. Interestingly, little is known regarding the mechanisms contributing to levothyroxine absorption in the gastrointestinal tract. Here, we aimed to determine whether the intestinal drug uptake transporter organic anion transporting polypeptide 2B1 (OATP2B1) may be involved in facilitating intestinal absorption of thyroid hormones. We also explored whether thyroid hormones regulate OATP2B1 gene expression. In cultured Madin-Darby Canine Kidney II/OATP2B1 cells and in OATP2B1-transfected Caco-2 cells, thyroid hormones were found to inhibit OATP2B1-mediated uptake of estrone-3-sulfate. Competitive counter-flow experiments evaluating the influence on the cellular accumulation of estrone-3-sulfate in the steady state indicated that thyroid hormones were substrates of OATP2B1. Additional evidence that thyroid hormones were OATP2B1 substrates was provided by OATP2B1-dependent stimulation of thyroid hormone receptor activation in cell-based reporter assays. Bidirectional transport studies in intestinal Caco-2 cells showed net absorptive flux of thyroid hormones, which was attenuated by the presence of the OATP2B1 inhibitor, atorvastatin. In intestinal Caco-2 and LS180 cells, but not in liver Huh-7 or HepG2 cells, OATP2B1 expression was induced by treatment with thyroid hormones. Reporter gene assays revealed thyroid hormone receptor α -mediated transactivation of the SLCO2B1 1b and the SLCO2B1 1e promoters. We conclude that thyroid hormones are substrates and transcriptional regulators of OATP2B1. These insights provide a potential mechanistic basis for oral levothyroxine dose variability and drug interactions. Copyright © 2018 by The American

  9. Active auxin uptake by zucchini membrane vesicles: quantitation using ESR volume and delta pH determinations

    International Nuclear Information System (INIS)

    Lomax, T.L.; Mehlhorn, R.J.; Briggs, W.R.

    1985-01-01

    Closed and pH-tight membrane vesicles prepared from hypocotyls of 5-day-old dark-grown seedlings of Cucurbita pepo accumulate the plant growth hormone indole-3-acetic acid along an imposed proton gradient (pH low outside, high inside). The use of electron paramagnetic spin probes permitted quantitation both of apparent vesicle volume and magnitude of the pH gradient. Under the experimental conditions used, hormone accumulation was at minimum 20-fold, a value 4 times larger than what one would predict if accumulation reflected only diffusional equilibrium at the measured pH gradient. It is concluded that hormone uptake is an active process, with each protonated molecule of hormone accompanied by an additional proton. Experiments with ionophores confirm that it is the pH gradient itself which drives the uptake

  10. Cadmium uptake by plants

    Energy Technology Data Exchange (ETDEWEB)

    Haghiri, F.

    1973-01-01

    Absorption of /sup 115m/Cd by soybean (Gylcine max l.) plants via foliar and root systems and translocation into the seed was determined. The uptake of /sup 115m/Cd by soybeans via the root system was more efficient than that of the foliar placement. Growth and Cd concentrations of soybean and wheat (Triticum aestivum l.) tops were influenced by soil-applied Cd. In both crops, the Cd concentration of plant tops increased while yield decreased with increasing levels of applied Cd. Cadmium toxicitiy began to occur in both crops at the lowest level of soil applied Cd (2.5 ppM). With soybean plants, Cd toxicity symptoms resembled fe chlorosis. For wheat plants there were no visual symptoms other than the studied growth. The relative concentration of Cd found in several vegetable crops varied depending on the plant species. The relative Cd concentration in descending order for various vegetables was lettuce (Lactuca sativa l.) > radish top (Raphanus sativus l.) > celery stalk (Apium graveolens l.) > celery leaves greater than or equal to green pepper (Capsicum frutescens l.) > radish roots.

  11. Kinetics of cellular uptake of viruses and nanoparticles via clathrin-mediated endocytosis

    Science.gov (United States)

    Banerjee, Anand; Berezhkovskii, Alexander; Nossal, Ralph

    2016-02-01

    Several viruses exploit clathrin-mediated endocytosis to gain entry into host cells. This process is also used extensively in biomedical applications to deliver nanoparticles (NPs) to diseased cells. The internalization of these nano-objects is controlled by the assembly of a clathrin-containing protein coat on the cytoplasmic side of the plasma membrane, which drives the invagination of the membrane and the formation of a cargo-containing endocytic vesicle. Current theoretical models of receptor-mediated endocytosis of viruses and NPs do not explicitly take coat assembly into consideration. In this paper we study cellular uptake of viruses and NPs with a focus on coat assembly. We characterize the internalization process by the mean time between the binding of a particle to the membrane and its entry into the cell. Using a coarse-grained model which maps the stochastic dynamics of coat formation onto a one-dimensional random walk, we derive an analytical formula for this quantity. A study of the dependence of the mean internalization time on NP size shows that there is an upper bound above which this time becomes extremely large, and an optimal size at which it attains a minimum. Our estimates of these sizes compare well with experimental data. We also study the sensitivity of the obtained results on coat parameters to identify factors which significantly affect the internalization kinetics.

  12. Iron uptake and increased intracellular enzyme activity follow host lactoferrin binding by Trichomonas vaginalis receptors

    Energy Technology Data Exchange (ETDEWEB)

    Peterson, K.M.; Alderete, J.F.

    1984-08-01

    Lactoferrin acquisition and iron uptake by pathogenic Trichomonas vaginalis was examined. Saturation binding kinetics were obtained for trichomonads using increasing amounts of radioiodinated lactoferrin, while no significant binding by transferrin under similar conditions was achieved. Only unlabeled lactoferrin successfully and stoichiometrically competed with 125I-labeled lactoferrin binding. Time course studies showed maximal lactoferrin binding by 30 min at 37 degrees C. Data suggest no internalization of bound lactoferrin. The accumulation of radioactivity in supernatants after incubation of T. vaginalis with 125I-labeled lactoferrin and washing in PBS suggested the presence of low affinity sites for this host macromolecule. Scatchard analysis indicated the presence of 90,000 receptors per trichomonad with an apparent Kd of 1.0 microM. Two trichomonad lactoferrin binding proteins were identified by affinity chromatography and immunoprecipitation of receptor-ligand complexes. A 30-fold accumulation of iron was achieved using 59Fe-lactoferrin when compared to the steady state concentration of bound lactoferrin. The activity of pyruvate/ferrodoxin oxidoreductase, an enzyme involved in trichomonal energy metabolism, increased more than sixfold following exposure of the parasites to lactoferrin, demonstrating a biologic response to the receptor-mediated binding of lactoferrin. These data suggest that T. vaginalis possesses specific receptors for biologically relevant host proteins and that these receptors contribute to the metabolic processes of the parasites.

  13. Iron uptake and increased intracellular enzyme activity follow host lactoferrin binding by Trichomonas vaginalis receptors

    International Nuclear Information System (INIS)

    Peterson, K.M.; Alderete, J.F.

    1984-01-01

    Lactoferrin acquisition and iron uptake by pathogenic Trichomonas vaginalis was examined. Saturation binding kinetics were obtained for trichomonads using increasing amounts of radioiodinated lactoferrin, while no significant binding by transferrin under similar conditions was achieved. Only unlabeled lactoferrin successfully and stoichiometrically competed with 125I-labeled lactoferrin binding. Time course studies showed maximal lactoferrin binding by 30 min at 37 degrees C. Data suggest no internalization of bound lactoferrin. The accumulation of radioactivity in supernatants after incubation of T. vaginalis with 125I-labeled lactoferrin and washing in PBS suggested the presence of low affinity sites for this host macromolecule. Scatchard analysis indicated the presence of 90,000 receptors per trichomonad with an apparent Kd of 1.0 microM. Two trichomonad lactoferrin binding proteins were identified by affinity chromatography and immunoprecipitation of receptor-ligand complexes. A 30-fold accumulation of iron was achieved using 59Fe-lactoferrin when compared to the steady state concentration of bound lactoferrin. The activity of pyruvate/ferrodoxin oxidoreductase, an enzyme involved in trichomonal energy metabolism, increased more than sixfold following exposure of the parasites to lactoferrin, demonstrating a biologic response to the receptor-mediated binding of lactoferrin. These data suggest that T. vaginalis possesses specific receptors for biologically relevant host proteins and that these receptors contribute to the metabolic processes of the parasites

  14. Radioiodine uptake following iodine-131 therapy for Graves' disease: an early indicator of need for retreatment

    Energy Technology Data Exchange (ETDEWEB)

    Carpentier, W.R.; Gilliland, P.F.; Piziak, V.K.; Petty, F.C.; McConnell, B.G.; Verdonk, C.A.; Ibarra, J.D.; Thompson, J.Q.

    1989-01-01

    Forty-five patients with Graves' disease were studied prospectively to determine if 24-hour I-131 uptake measurements alone or in combination with serum thyroid hormone levels at six weeks would determine the necessity for retreatment of the thyrotoxicosis. All patients with an I-131 uptake greater than 30% at six weeks required retreatment. No patient with an I-131 uptake of less than 15% required retreatment. Patients with uptakes between 15% and 30% were variable. An elevated free thyroxin index at 6 weeks is not helpful to determine which patients will remain thyrotoxic. Patients with a free thyroxin index within the normal range at six weeks can be predicted to be euthyroid by 12 weeks if their 24-hour I-131 uptake is between 15% and 30% and to be hypothyroid if their 24-hour I-131 uptake is below 15%. There was no difference between patient groups treated initially with antithyroid medication and those who were not.

  15. Diffuse and diffuse-plus-focal uptake in the thyroid gland identified by using FDG-PET. Prevalence of thyroid cancer and Hashimoto's thyroiditis

    International Nuclear Information System (INIS)

    Kurata, Seiji; Ishibashi, Masatoshi; Hiromatsu, Yuji; Kaida, Hayato; Miyake, Ikuyo; Uchida, Masafumi; Hayabuchi, Naofumi

    2007-01-01

    The objective of this study was to investigate and evaluate the prevalence of incidental thyroid diffuse and diffuse-plus-focal fluorine-18 fluorodeoxyglucose (FDG) uptake in healthy subjects who underwent cancer screening on positron emission tomography (PET) scan, and also to evaluate the prevalence of thyroid cancer and Hashimoto's thyroiditis. We carried out a retrospective review of 1626 subjects who underwent PET scanning at our institution. Diffuse uptake was defined as FDG uptake in the whole thyroid gland, whereas diffuse-plus-focal uptake was defined as a thyroid lesion with both diffuse uptake and focal FDG uptake. The maximum standardized uptake value of the thyroid lesions was recorded and reviewed. In each selected subject with positive thyroid FDG uptake, serum thyroid-stimulating hormone, thyroid hormone, and thyroid antibodies were measured. Fine needle aspiration cytology was performed on patients with a definite nodule using ultrasonography. Twenty-nine subjects (1.78%) were identified as having either diffuse FDG uptake (n=25, 1.53%) or diffuse-plus-focal FDG uptake (n=4, 0.24%). All subjects with diffuse FDG uptake were diagnosed as having Hashimoto's thyroiditis. In 1 of the 25 subjects with diffuse FDG uptake and two of the four with diffuse-plus-focal FDG uptake, histopathologic diagnosis showed papillary thyroid carcinoma associated with Hashimoto's thyroiditis. However, PET scan did not detect papillary carcinoma associated with Hashimoto's thyroiditis in one of the three subjects. Our results suggest that although diffuse FDG uptake usually indicates Hashimoto's thyroiditis, the risk of thyroid cancer must be recognized in both diffuse FDG uptake and diffuse-plus-focal FDG uptake on PET scan. (author)

  16. A nonpeptidyl growth hormone secretagogue.

    Science.gov (United States)

    Smith, R G; Cheng, K; Schoen, W R; Pong, S S; Hickey, G; Jacks, T; Butler, B; Chan, W W; Chaung, L Y; Judith, F

    1993-06-11

    A nonpeptidyl secretagogue for growth hormone of the structure 3-amino-3-methyl-N-(2,3,4,5-tetrahydro-2-oxo-1-([2'-(1H-tetrazol-5 -yl) (1,1'-biphenyl)-4-yl]methyl)-1H-1-benzazepin-3(R)-yl)-butanamid e (L-692,429) has been identified. L-692,429 synergizes with the natural growth hormone secretagogue growth hormone-releasing hormone and acts through an alternative signal transduction pathway. The mechanism of action of L-692,429 and studies with peptidyl and nonpeptidyl antagonists suggest that this molecule is a mimic of the growth hormone-releasing hexapeptide His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 (GHRP-6). L-692,429 is an example of a nonpeptidyl specific secretagogue for growth hormone.

  17. Thyroid Hormone, Cancer, and Apoptosis.

    Science.gov (United States)

    Lin, Hung-Yun; Chin, Yu-Tan; Yang, Yu-Chen S H; Lai, Husan-Yu; Wang-Peng, Jacqueline; Liu, Leory F; Tang, Heng-Yuan; Davis, Paul J

    2016-06-13

    Thyroid hormones play important roles in regulating normal metabolism, development, and growth. They also stimulate cancer cell proliferation. Their metabolic and developmental effects and growth effects in normal tissues are mediated primarily by nuclear hormone receptors. A cell surface receptor for the hormone on integrin [alpha]vβ3 is the initiation site for effects on tumor cells. Clinical hypothyroidism may retard cancer growth, and hyperthyroidism was recently linked to the prevalence of certain cancers. Local levels of thyroid hormones are controlled through activation and deactivation of iodothyronine deiodinases in different organs. The relative activities of different deiodinases that exist in tissues or organs also affect the progression and development of specific types of cancers. In this review, the effects of thyroid hormone on signaling pathways in breast, brain, liver, thyroid, and colon cancers are discussed. The importance of nuclear thyroid hormone receptor isoforms and of the hormone receptor on the extracellular domain of integrin [alpha]vβ3 as potential cancer risk factors and therapeutic targets are addressed. We analyze the intracellular signaling pathways activated by thyroid hormones in cancer progression in hyperthyroidism or at physiological concentrations in the euthyroid state. Determining how to utilize the deaminated thyroid hormone analog (tetrac), and its nanoparticulate derivative to reduce risks of cancer progression, enhance therapeutic outcomes, and prevent cancer recurrence is also deliberated. © 2016 American Physiological Society. Compr Physiol 6:1221-1237, 2016. Copyright © 2016 John Wiley & Sons, Inc.

  18. Missed hormonal contraceptives: new recommendations.

    Science.gov (United States)

    Guilbert, Edith; Black, Amanda; Dunn, Sheila; Senikas, Vyta

    2008-11-01

    To provide evidence-based guidance for women and their health care providers on the management of missed or delayed hormonal contraceptive doses in order to prevent unintended pregnancy. Medline, PubMed, and the Cochrane Database were searched for articles published in English, from 1974 to 2007, about hormonal contraceptive methods that are available in Canada and that may be missed or delayed. Relevant publications and position papers from appropriate reproductive health and family planning organizations were also reviewed. The quality of evidence is rated using the criteria developed by the Canadian Task Force on Preventive Health Care. This committee opinion will help health care providers offer clear information to women who have not been adherent in using hormonal contraception with the purpose of preventing unintended pregnancy. The Society of Obstetricians and Gynaecologists of Canada. SUMMARY STATEMENTS: 1. Instructions for what women should do when they miss hormonal contraception have been complex and women do not understand them correctly. (I) 2. The highest risk of ovulation occurs when the hormone-free interval is prolonged for more than seven days, either by delaying the start of combined hormonal contraceptives or by missing active hormone doses during the first or third weeks of combined oral contraceptives. (II) Ovulation rarely occurs after seven consecutive days of combined oral contraceptive use. (II) RECOMMENDATIONS: 1. Health care providers should give clear, simple instructions, both written and oral, on missed hormonal contraceptive pills as part of contraceptive counselling. (III-A) 2. Health care providers should provide women with telephone/electronic resources for reference in the event of missed or delayed hormonal contraceptives. (III-A) 3. In order to avoid an increased risk of unintended pregnancy, the hormone-free interval should not exceed seven days in combined hormonal contraceptive users. (II-A) 4. Back-up contraception should

  19. 99mTc-HMDP Bone Uptake Quantification and Plasma Osteocalcin, PTH Levels in Hemodialysis Patients

    International Nuclear Information System (INIS)

    Kim, Euy Neyng; Sohn, Hyung Sun; Bang, Chan Young; Chung, Soo Kyo; Kim, Choon Yul; Shinn, Kyung Sub; Park, Chul Whee; Chang, Yoon Sik

    1996-01-01

    In this preliminary study, plasma osteocalcin, PTH level and Tc-99m-HMDP (hydro-xymetylene diphosphonate) bone uptake(BU) were measured in 14 patients with chronic end-stage renal failure who were on maintenance hemodialysis. The aim of this study was to determine the difference of bone uptake between renal failure patients and normal volunteers, and to determine the correlation between bone uptake and osteocalcin a sensitive and specific marker of osteoblastic activity and PTH-a important hormone of bone metabolism. There was a statistically significant increase in 180 minute uptake in the patient group when compared to the normal volunteers while there was no statistically significant difference in 20 minute uptake. Plasma osteocalcin and PTH levels were also significantly elevated compared to normal values. But the correlation between osteocalcin, PTH and 20 and 180 minute bone uptake was not significant. In conclusion, our preliminary study suggests that, in chronic renal failure patients, 180 minute Tc-99m-HMDP bone uptake is increased significantly without direct correlation with serum osteocalcin or PTH levels. It seems that further study is needed to evaluate other unknown factors that may influence the direct correlation between bone uptake and plasma osteocalcin and PTH in patients with chronic renal failure.

  20. The CSF and arterial to internal jugular venous hormonal differences during exercise in humans

    DEFF Research Database (Denmark)

    Dalsgaard, Mads K; Ott, Peter; Dela, Flemming

    2004-01-01

    the brain (a-v diff) of hormones that could influence its carbohydrate uptake (n= 9). In addition, neuroendocrine activity and a potential uptake of hormones via the cerebrospinal fluid (CSF) were assessed by lumbar puncture postexercise and at rest (n= 6). Exercise increased the arterial concentration...... of noradrenaline and adrenaline, but there was no cerebral uptake. However, following exercise CSF noradrenaline was 1.4 (0.73-5.5) nmol l(-1), and higher than at rest, 0.3 (0.19-1.84) nmol l(-1) (P ...)(+) and its a-v diff, which increased from 1 (-12 to 5) to 17 (5-41) micromol l(-1) (P CSF NH(4)(+) was reduced to 7 (0-10) versus 11 (7-16) micromol l(-1) (P

  1. Methoxychlor affects multiple hormone signaling pathways in the largemouth bass (Micropterus salmoides) liver

    Science.gov (United States)

    Martyniuk, Christopher J.; Spade, Daniel J.; Blum, Jason L.; Kroll, Kevin J.; Denslow, Nancy D.

    2011-01-01

    Methoxychlor (MXC) is an organochlorine pesticide that has been shown to have estrogenic activity by activating estrogen receptors and inducing vitellogenin production in male fish. Previous studies report that exposure to MXC induces changes in mRNA abundance of reproductive genes in the liver and testes of largemouth bass (Micropterus salmoides). The objective of the present study was to better characterize the mode of action of MXC by measuring the global transcriptomic response in the male largemouth liver using an oligonucleotide microarray. Microarray analysis identified highly significant changes in the expression of 37 transcripts (p<0.001) (20 induced and 17 decreased) in the liver after MXC injection and a total of 900 expression changes (p<0.05) in transcripts with high homology to known genes. Largemouth bass estrogen receptor alpha (esr1) and androgen receptor (ar) were among the transcripts that were increased in the liver after MXC treatment. Functional enrichment analysis identified the molecular functions of steroid binding and androgen receptor activity as well as steroid hormone receptor activity as being significantly over-represented gene ontology terms. Pathway analysis identified c-fos signaling as being putatively affected through both estrogen and androgen signaling. This study provides evidence that MXC elicits transcriptional effects through the estrogen receptor as well as androgen receptor-mediated pathways in the liver. PMID:21276474

  2. L-tyrosine and L-DOPA as hormone-like regulators of melanocytes functions

    Science.gov (United States)

    Slominski, Andrzej; Zmijewski, Michal; Pawelek, John

    2011-01-01

    Summary Evidence reveals that L-tyrosine and L-DOPA, besides serving as substrates and intermediates of melanogenesis, are also bioregulatory agents acting not only as inducers and positive regulators of melanogenesis but also as regulators of other cellular functions. These can be mediated through action on specific receptors or through non-receptor mediated mechanisms. The substrate induced (L-tyrosine and/or L-DOPA) melanogenic pathway would autoregulate itself as well as it would regulate the melanocyte functions through activity of its structural or regulatory proteins and through intermediates of melanogenesis and melanin itself. Dissection of regulatory and autoregulatory elements of this process may elucidate how substrate induced autoregulatory pathways have evolved from prokaryotic or simple eukaryotic organisms to complex systems in vertebrates. This could substantiate older theory proposing that receptors for amino-acid derived hormones arose from the receptors for those amino acids, and that nuclear receptors evolved from primitive intracellular receptors binding nutritional factors or metabolic intermediates. PMID:21834848

  3. Technetium uptake by Sinapis Alba

    International Nuclear Information System (INIS)

    Mueller, H.; Ter Meer-Bekk, Ch.

    1986-01-01

    Transfer factors for pertechnetate uptake was determined for Sinapis Alba cultured hydroponically. For the freshly harvested, undried plants transfer factors were found between 13 and 40 depending on the growth period. (author)

  4. Diselenolane-mediated cellular uptake.

    Science.gov (United States)

    Chuard, Nicolas; Poblador-Bahamonde, Amalia I; Zong, Lili; Bartolami, Eline; Hildebrandt, Jana; Weigand, Wolfgang; Sakai, Naomi; Matile, Stefan

    2018-02-21

    The emerging power of thiol-mediated uptake with strained disulfides called for a move from sulfur to selenium. We report that according to results with fluorescent model substrates, cellular uptake with 1,2-diselenolanes exceeds uptake with 1,2-dithiolanes and epidithiodiketopiperazines with regard to efficiency as well as intracellular localization. The diselenide analog of lipoic acid performs best. This 1,2-diselenolane delivers fluorophores efficiently to the cytosol of HeLa Kyoto cells, without detectable endosomal capture as with 1,2-dithiolanes or dominant escape into the nucleus as with epidithiodiketopiperazines. Diselenolane-mediated cytosolic delivery is non-toxic (MTT assay), sensitive to temperature but insensitive to inhibitors of endocytosis (chlorpromazine, methyl-β-cyclodextrin, wortmannin, cytochalasin B) and conventional thiol-mediated uptake (Ellman's reagent), and to serum. Selenophilicity, the extreme CSeSeC dihedral angle of 0° and the high but different acidity of primary and secondary selenols might all contribute to uptake. Thiol-exchange affinity chromatography is introduced as operational mimic of thiol-mediated uptake that provides, in combination with rate enhancement of DTT oxidation, direct experimental evidence for existence and nature of the involved selenosulfides.

  5. Hormones and β-Agonists

    NARCIS (Netherlands)

    Ginkel, van L.A.; Bovee, T.F.H.; Blokland, M.H.; Sterk, S.S.; Smits, N.G.E.; Pleadin, Jelka; Vulić, Ana

    2016-01-01

    This chapter provides some updated information on contemporary methods for hormone and β-agonist analyses. It deals with the classical approaches for the effective detection and identification of exogenous hormones. The chapter examines specific problems related to control strategies for natural

  6. Studies on the T3 suppression test with reference to the thyrodial 123I uptake in Graves' disease

    International Nuclear Information System (INIS)

    Yamaguchi, Takahiko; Kobayashi, Isao; Yamaguchi, Yoshiyuki; Iwashita, Akira; Inukai, Toshihiko; Ohshima, Kihachi; Shimomura, Yohnosuke; Kobayashi, Setsuo

    1990-01-01

    Eighty-three patients with Graves' disease had been treated with methylmercaptoimidazole (MMI). They were prescribed a maintenance dose of antithyroid drug (MMI, 5 mg/day) at the time of a T 3 suppression test. The 3-hour and 24-hour thyroidal 123 I uptake after T 3 administration (75 μg/day, 2 weeks) were measured (post T 3 uptake). In 38 patients whose post T 3 uptake was below 35% in post T 3 24-hour uptake, treatment was stopped. The T 3 suppression test was then repeated 1 and 3 months later. During a one-year follow up, 26 remained well, while 12 relapsed within 6 to 12 months. We have observed a good correlation between 3-hour uptake and 24-hour uptake of 123 I after T 3 administration (r=0.847, p 3 suppression, most patients with MMI withdrawal produced a marked overshoot of post T 3 3-hour and 24-hour uptake at one month. Retrospective analysis indicated that there was no significant difference in circulating thyroid hormone levels between remission and relapse groups. The present study provides evidence that 3-hour uptake values are able to be substituted for 24-hour uptake values during a T 3 suppression test. In addition, overshoot of thyroidal uptake after antithyroid drug withdrawal was observed in 3-hour values, similar to 24-hour values. (author)

  7. Hormone Replacement Therapy and Your Heart

    Science.gov (United States)

    Hormone replacement therapy and your heart Are you taking — or considering — hormone therapy to treat bothersome menopausal symptoms? Understand ... you. By Mayo Clinic Staff Long-term hormone replacement therapy used to be routinely prescribed for postmenopausal ...

  8. Monoclonal antibody to the type I insulin-like growth factor (IGF-I) receptor blocks IGF-I receptor-mediated DNA synthesis: clarification of the mitogenic mechanisms of IGF-I and insulin in human skin fibroblasts

    International Nuclear Information System (INIS)

    Flier, J.S.; Usher, P.; Moses, A.C.

    1986-01-01

    Insulin and insulin-like growth factor type I (IGF-I) stimulate an overlapping spectrum of biological responses in human skin fibroblasts. Although insulin and IGF-I are known to stimulate the incorporation of [ 3 H]thymidine into DNA in these cells, the identify of the receptor(s) that mediates this effect has not been fully clarified. The mouse anti-human IGF-I receptor antibody αIR-3 binds with specificity to IGF-I but not to insulin receptors in human placental membranes; it also specifically inhibits the binding of 125 I-labeled IGF-I but not 125 I-labeled insulin to suspensions of human skin fibroblasts in a dose-dependent manner. αIR-3 competitively inhibits IGF-I-mediated stimulation of [ 3 H]thymidine incorporation into DNA. This inhibition is dependent on the concentration of αIR-3 and in the presence of a fixed antibody concentration can be partially overcome by high concentrations of IGF-I. In contrast, at concentrations of 3 H]thymidine incorporation is not inhibited by αIR-3. However, the incremental effects of higher concentrations (> 1 μg/ml) of insulin on [ 3 H]thymidine incorporation are inhibited by αIR-3. αIR-3 is a highly specific antagonist of IGF-I receptor-mediated mitogenesis in human skin fibroblasts. By using this antibody, it is shown directly that insulin can act through the IGF-I receptor to stimulate DNA synthesis but can also activate this effect through the insulin receptor itself

  9. Effect of parathyroid hormone on transport by toad and turtle bladder

    International Nuclear Information System (INIS)

    Sabatini, S.; Kurtzman, N.A.

    1987-01-01

    The authors recently demonstrated that parathyroid hormone (PTH) inhibited both vasopressin- and cyclic AMP-stimulated water transport in the toad bladder. This was associated with an increase in calcium uptake by isolated epithelial cells. They postulated that PTH exerts its action on H 2 O transport by directly stimulating calcium uptake. The current study was designed to compare the effects of PTH and the calcium ionophore, A23187, on H 2 O and Na transport and Hμ secretion in toad and turtle bladders. In toad bladder, PTH and A23187 decreased arginine vasopressin (AVP)-stimulated H 2 O flow and short-circuit current (SCC) after 60 min serosal incubation. In turtle bladder A23187 decreased SCC to 79.3 +/- 3.6% of base line (P + secretion in turtle bladders. Both PTH and A23187 increased 45 Ca uptake in toad bladder epithelial cells; only A23187 increased 45 Ca uptake in the turtle bladder. The different action of PTH in these two membranes, compared with that of the calcium ionophore, illustrates the selectivity of PTH on membrane transport. PTH increases calcium uptake and decreases transport only in a hormone-sensitive epithelium, whereas the ionophore works in virtually all living membranes. The mode of action of these two agents to increase calcium uptake is, therefore likely different

  10. Effect of pituitary gonadotrophins on tritiated thymidine uptake by rat ovary

    International Nuclear Information System (INIS)

    Nakano, Ryosuke; Mizuno, Tadayoshi; Katayama, Kazuaki; Hayashi, Kaname; Tojo, Shimpei

    1975-01-01

    The effect of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) on the follicular growth in the ovary of the hypophysectomized rat was investigated using autoradiography. The numbers of DNA-synthesizing nuclei in the granulosa cell were measured by autoradiography after flashlabelling with tritiated ( 3 H) thymidine. The frequency of 3 H-thymidine labelled nuclei in the granulosa cell enhanced in the presence of FSH. In contrast, LH had no significant effect on thymidine uptake. The result suggests that FSH stimulates follicle cell division, whereas LH does not. (orig.) [de

  11. Strong association of epidermal growth factor receptor status with breast cancer FDG uptake

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Joohee; Moon, Seung Hwan; Hyun, Seung Hyup; Cho, Young Seok; Choi, Joon Young; Kim, Byung-Tae; Lee, Kyung-Han [Sungkyunkwan University School of Medicine, Department of Nuclear Medicine, Samsung Medical Center, Seoul (Korea, Republic of); Lee, Eun Jeong [Seoul Medical Center, Department of Nuclear Medicine, Seoul (Korea, Republic of); Kim, Seokhwi [Sungkyunkwan University School of Medicine, Department of Pathology, Samsung Medical Center, Seoul (Korea, Republic of)

    2017-08-15

    Imaging tumor FDG uptake could complement breast cancer biomarkers of risk and treatment response. Although breast cancer FDG uptake is reputedly influenced by major biomarker states, the role of epidermal growth factor receptor (EGFR) expression remains largely unexplored. This is a retrospective study that included 499 patients with primary breast cancer at initial presentation. Tumor FDG uptake was measured on pretreatment PET/CT as maximum standardized uptake value (SUVmax), and biomarkers were assessed by immunohistochemistry of tumor tissue. Regression analysis was performed for predictors of high tumor FDG uptake (SUVmax ≥ 8.6). SUVmax was higher in ER- (36.5%; 11.2 ± 6.0 vs. 8.3 ± 5.3), PR- (42.3%; 10.9 ± 6.0 vs. 8.2 ± 5.2), and triple-negative tumors (19.8%; 12.0 ± 6.9 vs. 8.7 ± 5.2; all p < 0.0001). EGFR expression (28.5%) was more frequent in ER-, PR-, triple-negative, cytokeratin 5/6 (CK5/6) + and mutant P53 (mP53) + tumors (all p < 0.0001). EGFR+ was associated with higher SUVmax among all tumors (11.9 ± 6.0 vs. 8.3 ± 5.3), ER- tumors (p < 0.0001), PR- and + tumors (p < 0.0001 and 0.027), hormone receptor- and + tumors (p < 0.0001 and 0.004), human epidermal growth factor receptor 2 (HER2)- and + tumors (p < 0.0001 and 0.006), non-triple negative tumors (p < 0.0001), CK5/6- and + tumors (p = 0.021 and <0.0001), and mP53- and + tumors (p < 0.0001 and 0.008). Tumors had high FDG uptake in 73.2% of EGFR+ and 40.6% of EGFR- tumors. On regression analysis, significant multivariate predictors of high tumor FDG uptake were large size, EGFR+ and CK5/6+ for the entire subjects, and EGFR+ and CK5/6+ for ER- and hormone receptor negative subgroups. High FDG uptake was able to sub-stratify EGFR+ tumors that were more likely to be ER- and CK5/6+, and EGFR- tumors more likely to be mP53 +. Primary breast tumor FDG uptake is strongly influenced by EGFR status beyond that by other major biomarkers including hormone receptor and HER2 status, and EGFR

  12. Epidermal growth factor (EGF) inhibits stimulated thyroid hormone secretion in the mouse

    International Nuclear Information System (INIS)

    Ahren, B.

    1987-01-01

    It is known that epidermal growth factor (EGF) inhibits iodide uptake in the thyroid follicular cells and lowers plasma levels of thyroid hormones upon infusion into sheep and ewes. In this study, the effects of EGF on basal and stimulated thyroid hormone secretion were investigated in the mouse. Mice were pretreated with 125 I and thyroxine; the subsequent release of 125 I is an estimation of thyroid hormone secretion. It was found that basal radioiodine secretion was not altered by intravenous injection of EGF (5 micrograms/animal). However, the radioiodine secretion stimulated by both TSH (120 microU/animal) and vasoactive intestinal peptide (VIP; 5 micrograms/animal) were inhibited by EGF (5 micrograms/animal). At a lower dose level (0.5 microgram/animal), EGF had no influence on stimulated radioiodine secretion. In conclusion, EGF inhibits stimulated thyroid hormone secretion in the mouse

  13. Cytotoxicity and cellular uptake of tri-block copolymer nanoparticles with different size and surface characteristics

    Directory of Open Access Journals (Sweden)

    Bhattacharjee Sourav

    2012-04-01

    Full Text Available Abstract Background Polymer nanoparticles (PNP are becoming increasingly important in nanomedicine and food-based applications. Size and surface characteristics are often considered to be important factors in the cellular interactions of these PNP, although systematic investigations on the role of surface properties on cellular interactions and toxicity of PNP are scarce. Results Fluorescent, monodisperse tri-block copolymer nanoparticles with different sizes (45 and 90 nm and surface charges (positive and negative were synthesized, characterized and studied for uptake and cytotoxicity in NR8383 and Caco-2 cells. All types of PNP were taken up by the cells. The positive smaller PNP45 (45 nm showed a higher cytotoxicity compared to the positive bigger PNP90 (90 nm particles including reduction in mitochondrial membrane potential (ΔΨm, induction of reactive oxygen species (ROS production, ATP depletion and TNF-α release. The negative PNP did not show any cytotoxic effect. Reduction in mitochondrial membrane potential (ΔΨm, uncoupling of the electron transfer chain in mitochondria and the resulting ATP depletion, induction of ROS and oxidative stress may all play a role in the possible mode of action for the cytotoxicity of these PNP. The role of receptor-mediated endocytosis in the intracellular uptake of different PNP was studied by confocal laser scanning microscopy (CLSM. Involvement of size and charge in the cellular uptake of PNP by clathrin (for positive PNP, caveolin (for negative PNP and mannose receptors (for hydroxylated PNP were found with smaller PNP45 showing stronger interactions with the receptors than bigger PNP90. Conclusions The size and surface characteristics of polymer nanoparticles (PNP; 45 and 90 nm with different surface charges play a crucial role in cellular uptake. Specific interactions with cell membrane-bound receptors (clathrin, caveolin and mannose leading to cellular internalization were observed to depend on

  14. Root uptake of transuranic elements

    International Nuclear Information System (INIS)

    Schulz, R.K.

    1977-01-01

    The uptake of elements by plant roots is one of the important pathways of entry of many elements into the food chain of man. Data are cited showing plutonium concentration ratios, plant/soil, ranging from 10 -10 to 10 -3 . Concentration ratios for americium range from 10 -7 to 10 +1 . Limited experiments with curium and neptunium indicate that root uptake of curium is similar to that of americium and that plant uptake of neptunium is substantially larger than that of curium and americium. The extreme ranges of concentration ratios cited for plutonium and americium are due to a number of causes. Experimental conditions such as very intensive cropping will lead to abnormally high concentration ratios. In some experiments, addition of chelating agents markedly increased plant root uptake of transuranic elements. Particle size and composition of the source material influenced uptake of the transuranics by plants. Translocation within the plant, and soil factors such as pH and organic matter content, all affect concentration ratios

  15. Gastroenteropancreatic hormonal changes during exercise

    DEFF Research Database (Denmark)

    Hilsted, J; Galbo, H; Sonne, B

    1980-01-01

    Peripheral plasma concentrations of gastroenteropancreatic peptides were measured during a 3-h period of bicycle exercise at 40% of maximal oxygen uptake in six normal men. Marked increases (P......Peripheral plasma concentrations of gastroenteropancreatic peptides were measured during a 3-h period of bicycle exercise at 40% of maximal oxygen uptake in six normal men. Marked increases (P...

  16. Thyrotoxic Graves' disease with normal thyroidal technetium-99m pertechnetate uptake

    Energy Technology Data Exchange (ETDEWEB)

    Ikekubo, Katsuji; Hino, Megumu; Ito, Hidetomi; Koh, Toshikiyo; Ishihara, Takashi; Kurahachi, Hiroyuki (Kobe City General Hospital (Japan)); Kasagi, Kanji; Hidaka, Akinari; Mori, Toru

    1990-07-01

    We saw 24 thyrotoxic Graves' patients with normal thyroidal uptake of technetium-99m pertechnetate ({sup 99m}Tc) out of 201 untreated thyrotoxic Graves' patients seen over 4 years. The clinical and laboratory findings for these patients were studied and analyzed. Thyroid uptake and scintigraphic examinations by means of {sup 99m}Tc, TBII and TSab activity measurement clearly distinguished these patients from other thyrotoxic disorders (destruction-induced thyrotoxicosis and autonomously functioning thyroid lesions). Different from other disorders, these patients had not lower but normal thyroid uptake and also showed diffuse and discrete trapping into the enlarged glands. These patients had significantly smaller goiters, a lower serum thyroid hormone level, and lower TBII and TSab activity, when compared with other high {sup 99m}Tc uptake groups with Graves' disease, and their condition could be easily controlled with small amounts of antithyroid drugs. Our study indicates that thyrotoxic Graves' disease with normal {sup 99m}Tc uptake exists and {sup 99m}Tc uptake study and TBII activity measurement is very useful for the diagnosis. The normal {sup 99m}Tc uptake thyrotoxic Graves' patient might be early stage patients with general Graves' disease and their early discrimination from general Graves' patients is very advantageous for treatment and prognosis. (author).

  17. Interactions between hormones and epilepsy.

    Science.gov (United States)

    Taubøll, Erik; Sveberg, Line; Svalheim, Sigrid

    2015-05-01

    There is a complex, bidirectional interdependence between sex steroid hormones and epilepsy; hormones affect seizures, while seizures affect hormones thereby disturbing reproductive endocrine function. Both female and male sex steroid hormones influence brain excitability. For the female sex steroid hormones, progesterone and its metabolites are anticonvulsant, while estrogens are mainly proconvulsant. The monthly fluctuations in hormone levels of estrogen and progesterone are the basis for catamenial epilepsy described elsewhere in this issue. Androgens are mainly anticonvulsant, but the effects are more varied, probably because of its metabolism to, among others, estradiol. The mechanisms for the effects of sex steroid hormones on brain excitability are related to both classical, intracellularly mediated effects, and non-classical membrane effects due to binding to membrane receptors. The latter are considered the most important in relation to epilepsy. The different sex steroids can also be further metabolized within the brain to different neurosteroids, which are even more potent with regard to their effect on excitability. Estrogens potentiate glutamate responses, primarily by potentiating NMDA receptor activity, but also by affecting GABA-ergic mechanisms and altering brain morphology by increasing dendritic spine density. Progesterone and its main metabolite 5α-pregnan-3α-ol-20-one (3α-5α-THP) act mainly to enhance postsynaptic GABA-ergic activity, while androgens enhance GABA-activated currents. Seizures and epileptic discharges also affect sex steroid hormones. There are close anatomical connections between the temporolimbic system and the hypothalamus controlling the endocrine system. Several studies have shown that epileptic activity, especially mediated through the amygdala, alters reproductive function, including reduced ovarian cyclicity in females and altered sex steroid hormone levels in both genders. Furthermore, there is an asymmetric

  18. contribution of growth hormone-releasing hormone and

    African Journals Online (AJOL)

    The strategy used was to stimulate GH secretion in 8 young ... treatment with two oral doses of 50 mg atenolol (to inhibit .... had normal baseline thyroid-stimulating hormone (TSH) ..... production rate of 14% per decade has been documented.'".

  19. Sex Hormones and Ischemic Stroke

    DEFF Research Database (Denmark)

    Holmegard, Haya N; Nordestgaard, Børge G; Jensen, Gorm B

    2016-01-01

    CONTEXT AND OBJECTIVE: Whether endogenous sex hormones are associated with ischemic stroke (IS) is unclear. We tested the hypothesis that extreme concentrations of endogenous sex hormones are associated with risk of IS in the general population. DESIGN, SETTING, AND PARTICIPANTS: Adult men (n...... = 4615) and women (n = 4724) with measurements of endogenous sex hormones during the 1981-1983 examination of the Copenhagen City Heart Study, Denmark, were followed for up to 29 years for incident IS, with no loss to follow-up. Mediation analyses assessed whether risk of IS was mediated through...

  20. Opioid receptor mediated anticonvulsant effect of pentazocine.

    Science.gov (United States)

    Khanna, N; Khosla, R; Kohli, J

    1998-01-01

    Intraperitoneal (i.p.) administration of (+/-) pentazocine (10, 30 & 50 mg/kg), a Sigma opioid agonist, resulted in a dose dependent anticonvulsant action against maximal electroshock seizures in mice. This anticonvulsant effect of pentazocine was not antagonized by both the doses of naloxone (1 and 10 mg/kg) suggesting thereby that its anticonvulsant action is probably mediated by Sigma opiate binding sites. Its anticonvulsant effect was potentiated by both the anticonvulsant drugs viz. diazepam and diphenylhydantoin. Morphine, mu opioid agonist, on the other hand, failed to protect the animals against maximal electroshock seizures when it was given in doses of 10-40 mg/kg body wt.

  1. Molecular Mechanisms of Dopamine Receptor Mediated Neuroprotection

    National Research Council Canada - National Science Library

    Sealfon, Stuart

    2000-01-01

    ... of the cellular changes characteristic of this process. Evidence from our laboratory and others suggest that activation of dopamine receptors can oppose the induction of apoptosis in dopamine neurons...

  2. Inositol trisphosphate receptor mediated spatiotemporal calcium signalling.

    Science.gov (United States)

    Miyazaki, S

    1995-04-01

    Spatiotemporal Ca2+ signalling in the cytoplasm is currently understood as an excitation phenomenon by analogy with electrical excitation in the plasma membrane. In many cell types, Ca2+ waves and Ca2+ oscillations are mediated by inositol 1,4,5-trisphosphate (IP3) receptor/Ca2+ channels in the endoplasmic reticulum membrane, with positive feedback between cytosolic Ca2+ and IP3-induced Ca2+ release creating a regenerative process. Remarkable advances have been made in the past year in the analysis of subcellular Ca2+ microdomains using confocal microscopy and of Ca2+ influx pathways that are functionally coupled to IP3-induced Ca2+ release. Ca2+ signals can be conveyed into the nucleus and mitochondria. Ca2+ entry from outside the cell allows repetitive Ca2+ release by providing Ca2+ to refill the endoplasmic reticulum stores, thus giving rise to frequency-encoded Ca2+ signals.

  3. Cellular Uptake and Delivery of Myeloperoxidase to Lysosomes Promote Lipofuscin Degradation and Lysosomal Stress in Retinal Cells*

    Science.gov (United States)

    Yogalingam, Gouri; Lee, Amanda R.; Mackenzie, Donald S.; Maures, Travis J.; Rafalko, Agnes; Prill, Heather; Berguig, Geoffrey Y.; Hague, Chuck; Christianson, Terri; Bell, Sean M.; LeBowitz, Jonathan H.

    2017-01-01

    Neutrophil myeloperoxidase (MPO) catalyzes the H2O2-dependent oxidation of chloride anion to generate hypochlorous acid, a potent antimicrobial agent. Besides its well defined role in innate immunity, aberrant degranulation of neutrophils in several inflammatory diseases leads to redistribution of MPO to the extracellular space, where it can mediate tissue damage by promoting the oxidation of several additional substrates. Here, we demonstrate that mannose 6-phosphate receptor-mediated cellular uptake and delivery of MPO to lysosomes of retinal pigmented epithelial (RPE) cells acts to clear this harmful enzyme from the extracellular space, with lysosomal-delivered MPO exhibiting a half-life of 10 h. Lysosomal-targeted MPO exerts both cell-protective and cytotoxic functions. From a therapeutic standpoint, MPO catalyzes the in vitro degradation of N-retinylidene-N-retinylethanolamine, a toxic form of retinal lipofuscin that accumulates in RPE lysosomes and drives the pathogenesis of Stargardt macular degeneration. Furthermore, chronic cellular uptake and accumulation of MPO in lysosomes coincides with N-retinylidene-N-retinylethanolamine elimination in a cell-based model of macular degeneration. However, lysosomal-delivered MPO also disrupts lysosomal acidification in RPE cells, which coincides with nuclear translocation of the lysosomal stress-sensing transcription factor EB and, eventually, cell death. Based on these findings we predict that under periods of acute exposure, cellular uptake and lysosomal degradation of MPO mediates elimination of this harmful enzyme, whereas chronic exposure results in progressive accumulation of MPO in lysosomes. Lysosomal-accumulated MPO can be both cell-protective, by promoting the degradation of toxic retinal lipofuscin deposits, and cytotoxic, by triggering lysosomal stress and cell death. PMID:28115520

  4. Cellular Uptake and Delivery of Myeloperoxidase to Lysosomes Promote Lipofuscin Degradation and Lysosomal Stress in Retinal Cells.

    Science.gov (United States)

    Yogalingam, Gouri; Lee, Amanda R; Mackenzie, Donald S; Maures, Travis J; Rafalko, Agnes; Prill, Heather; Berguig, Geoffrey Y; Hague, Chuck; Christianson, Terri; Bell, Sean M; LeBowitz, Jonathan H

    2017-03-10

    Neutrophil myeloperoxidase (MPO) catalyzes the H 2 O 2 -dependent oxidation of chloride anion to generate hypochlorous acid, a potent antimicrobial agent. Besides its well defined role in innate immunity, aberrant degranulation of neutrophils in several inflammatory diseases leads to redistribution of MPO to the extracellular space, where it can mediate tissue damage by promoting the oxidation of several additional substrates. Here, we demonstrate that mannose 6-phosphate receptor-mediated cellular uptake and delivery of MPO to lysosomes of retinal pigmented epithelial (RPE) cells acts to clear this harmful enzyme from the extracellular space, with lysosomal-delivered MPO exhibiting a half-life of 10 h. Lysosomal-targeted MPO exerts both cell-protective and cytotoxic functions. From a therapeutic standpoint, MPO catalyzes the in vitro degradation of N -retinylidene- N -retinylethanolamine, a toxic form of retinal lipofuscin that accumulates in RPE lysosomes and drives the pathogenesis of Stargardt macular degeneration. Furthermore, chronic cellular uptake and accumulation of MPO in lysosomes coincides with N -retinylidene- N -retinylethanolamine elimination in a cell-based model of macular degeneration. However, lysosomal-delivered MPO also disrupts lysosomal acidification in RPE cells, which coincides with nuclear translocation of the lysosomal stress-sensing transcription factor EB and, eventually, cell death. Based on these findings we predict that under periods of acute exposure, cellular uptake and lysosomal degradation of MPO mediates elimination of this harmful enzyme, whereas chronic exposure results in progressive accumulation of MPO in lysosomes. Lysosomal-accumulated MPO can be both cell-protective, by promoting the degradation of toxic retinal lipofuscin deposits, and cytotoxic, by triggering lysosomal stress and cell death. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  5. Lactate, Glucose and Oxygen Uptake in Human Brain During Recovery from Maximal Exercise

    DEFF Research Database (Denmark)

    Kojiro, I.; Schmalbruch, I.K.; Quistorff, B.

    1999-01-01

    Skeletal muscle, brain lactate uptake, brain oxygen uptake, energy metabolism, brain glucose uptake......Skeletal muscle, brain lactate uptake, brain oxygen uptake, energy metabolism, brain glucose uptake...

  6. HORMONAL TREATMENT IN UROGYNECOLOGY

    Directory of Open Access Journals (Sweden)

    Adolf Lukanović

    2018-02-01

    Full Text Available Background. Hormonal treatment in urogynecology is based on the knowledge, that urinary and reproductive tracts have common embriologic origin and are also linked anatomically and functionally. Both systems are functioning and changing due to sex steroids influence. Decreased estrogen concentrations are connected to metabolic and trophic changes in all organs with estrogen receptors, i.e. also in urogenital tract. Atrophy of urogenital system in postmenopause is a common causative factor for stress urinary incontinence (SUI and urge incontinence (UUI. In both estrogen replacement treatment have been introduced, but meta-analyses of the available literature indicate that estrogen therapy is effective only if given vaginaly. Recurrent urinary tract infections (RUTI occur in postmenopause often as a consequence of structural changes in urinary and reproductive tract to lowered immune protection and colonization with eneterobacteria. In RUTI too, estrogen replacement treatment have been used with the results similar to those with SUI and UUI. Effectiveness of estrogen treatment was evident only in topically applied vaginaly, while oral administration has the same effectiveness as placebo. Conclusions. Structural changes in urogenital tract in postmenopause are the results of estrogen depletion. Estrogen replacement is effective in cases of SUI, UUI and RUTI if it is applied topicaly, the efffect being influenced by the type of estrogen used and duration of treatment.

  7. The frequency and spectrum of thymus 2-[fluorine-18] fluoro-2-deoxy-D-glucose uptake patterns in hyperthyroidism patients.

    Science.gov (United States)

    Chen, Yen-Kung; Yeh, Chia-Lu; Chen, Yen-Ling; Wang, Su-Chen; Cheng, Ru-Hwa; Kao, Pan-Fu

    2011-10-01

    Thymic hyperplasia is associated with hyperthyroidism. Increased thymus 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) uptake in hyperthyroidism patients has been reported. The aim of this study was to analyze the FDG positron emission tomography (PET) thymus uptake spectrum in patients with active hyperthyroidism with correlation with serum hormones. The prospective study included FDG PET scans from 65 hyperthyroidism patients and 30 subjects with euthyroid status as control group. The intensity of FDG uptake in thyroid and thymus regions was graded subjectively on a five-point scale and semi-quantitatively by measuring standard uptake value (SUV). Correlation coefficient between thymus SUV and serum thyroxine, triiodothyronine, thyrotropin, thyroid peroxidase antibodies (TPO Ab), thyrotropin receptor autoantibody (TR Ab), and thymulin were analyzed. Among 65 hyperthyroidism patients, 30 (46.2%) and 39 (60%) patients showed thyroid and thymus FDG uptake, respectively. The frequency of thymus uptake FDG was high in patients younger than age 40 (28/31, 90.3%). The patterns of the thymic FDG uptake include inverted V or triangular, separated triangular, united nontriangular, unilateral right or left extension, and focal midline. Focal midline FDG uptake was the most common pattern (15/39, 38.5%). None of the control group showed thymus FDG uptake. The correlation coefficient between the FDG uptake SUV levels in thymus and serum hormones, thyrotropin, TPO Ab, TR Ab, and thymulin levels were all low (P > .05). In FDG PET scan, thymus activity was common in hyperthyroidism patients; this should not be misdiagnosed as a malignancy in patients exhibiting weight loss. Copyright © 2011 AUR. Published by Elsevier Inc. All rights reserved.

  8. Measurement of the incretin hormones

    DEFF Research Database (Denmark)

    Kuhre, Rune Ehrenreich; Wewer Albrechtsen, Nicolai Jacob; Hartmann, Bolette

    2015-01-01

    The two incretin hormones, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), are secreted from the gastrointestinal tract in response to meals and contribute to the regulation of glucose homeostasis by increasing insulin secretion. Assessment of plasma concentrat......The two incretin hormones, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), are secreted from the gastrointestinal tract in response to meals and contribute to the regulation of glucose homeostasis by increasing insulin secretion. Assessment of plasma...... concentrations of GLP-1 and GIP is often an important endpoint in both clinical and preclinical studies and, therefore, accurate measurement of these hormones is important. Here, we provide an overview of current approaches for the measurement of the incretin hormones, with particular focus on immunological...

  9. Controversies in hormone replacement therapy

    Directory of Open Access Journals (Sweden)

    A. Baziad

    2001-09-01

    Full Text Available Deficiency of estrogen hormone will result in either long-term or short-term health problems which may reduce the quality of life. There are numerous methods by which the quality of female life can be achieved. Since the problems occuring are due to the deficiency of estrogen hormone, the appropriate method to tackle the problem is by administration of estrogen hormone. The administration of hormone replacement therapy (HRT with estrogen may eliminate climacteric complaints, prevent osteoporosis, coronary heart disease, dementia, and colon cancer. Although HRT has a great deal of advantage, its use is still low and may result in controversies. These controversies are due to fact that both doctor and patient still hold on to the old, outmoded views which are not supported by numerous studies. Currently, the use of HRT is not only based on experience, or temporary observation, but more on evidence based medicine. (Med J Indones 2001; 10: 182-6Keywords: controversies, HRT

  10. Network identification of hormonal regulation.

    Directory of Open Access Journals (Sweden)

    Daniel J Vis

    Full Text Available Relations among hormone serum concentrations are complex and depend on various factors, including gender, age, body mass index, diurnal rhythms and secretion stochastics. Therefore, endocrine deviations from healthy homeostasis are not easily detected or understood. A generic method is presented for detecting regulatory relations between hormones. This is demonstrated with a cohort of obese women, who underwent blood sampling at 10 minute intervals for 24-hours. The cohort was treated with bromocriptine in an attempt to clarify how hormone relations change by treatment. The detected regulatory relations are summarized in a network graph and treatment-induced changes in the relations are determined. The proposed method identifies many relations, including well-known ones. Ultimately, the method provides ways to improve the description and understanding of normal hormonal relations and deviations caused by disease or treatment.

  11. Growth Hormone Deficiency in Children

    Science.gov (United States)

    ... your child if you see signs of poor self-esteem or sadness that could be related to being ... December 2011 The Hormone Health Network offers free, online resources based on the most advanced clinical and ...

  12. Impaired transport of thyroid hormones into livers of obese (ob/ob) mice

    International Nuclear Information System (INIS)

    Hillgartner, F.B.; Romsos, D.R.

    1988-01-01

    Obese (ob/ob) mice exhibit impaired hepatic thyroid hormone action that is mediated, at least in part, by a reduced nuclear 3,5,3'-triiodothyronine (T 3 ) receptor occupancy. The possibility that lowered occupancy in obese mice may be caused by decreased transport of T 3 across the hepatic plasma membrane was examined by measuring the unidirectional influx of [ 125 I]T 3 into livers of 8- to 10-wk-old obese and lean mice using a tissue-sampling portal vein-injection technique. Influx of [ 125 I]thyroxine (T 4 ), a substrate for T 4 5'-deiodinase, was also measured. Unidirectional clearance of T 3 and T 4 was 64 and 80% lower, respectively, in obese mice than in lean mice. Hepatic T 3 and T 4 uptake was nonsaturable in both lean and obese mice, suggesting that transport occurs by lipid-mediated free diffusion. Clearance of another lipid-soluble hormone, hydrocortisone, was also lower in obese mice than in lean mice. Decreased membrane permeability to the above hormones in obese mice may result from reported changes in membrane lipid composition. In conclusion, decreased hepatic thyroid hormone uptake may contribute to impaired thyroid hormone action and T 3 production in livers of obese mice

  13. Modulation of hepatic reticuloendothelial system phagocytosis by pancreatic hormones.

    Science.gov (United States)

    Cornell, R P; McClellan, C C

    1982-12-01

    Experiments were conducted to determine the influence of the pancreatic hormones insulin, glucagon, and somatostatin on reticuloendothelial system (RES) phagocytosis both in vivo and in the isolated perfused livers of rats. Chronic pancreatic hormonal treatment consisted of twice daily injections SC of NPH insulin with doses ranging from 0.75 U on day 1 to 9.0 U on day 13 and unchanged doses of glucagon (200 micrograms) and somatostatin (50 micrograms). Chronic treatment with insulin significantly depressed by 48% intravascular phagocytosis of colloidal carbon administered IV at a dose of 8 mg/100 g, while glucagon and somatostatin stimulated macrophage endocytic function by 32% and 26%, respectively, compared to the control value. Acute treatment with the three pancreatic hormones at 30 min prior to carbon administration similarly produced insulin depression as well as glucagon and somatostatin stimulation of RES phagocytosis. Addition of the three hormones at near physiologic concentrations (20 ng/ml for insulin, 10 ng/ml for glucagon, and 5 ng/ml for somatostatin) to the recirculating perfusate of isolated perfused rat livers simultaneous with 24 mg of colloidal carbon likewise resulted in phagocytic reduction after insulin and enhancement after glucagon and somatostatin. Experiments involving insulin in vitro with isolated perfused livers as well as glucose replacement therapy concomitant with insulin in vivo demonstrated that hypoglycemia is not necessary for phagocytic depression by insulin while severe hypoglycemia in the perfusion medium is sufficient to depress carbon uptake by isolated perfused livers independent of insulin. Both pancreatic hormones and the level of glycemia seem to be important in modulating hepatic reticuloendothelial system phagocytosis.

  14. Ghrelin: much more than a hunger hormone

    Science.gov (United States)

    Ghrelin is a multifaceted gut hormone that activates its receptor, growth hormone secretagogue receptor (GHS-R). Ghrelin's hallmark functions are its stimulatory effects on growth hormone release, food intake and fat deposition. Ghrelin is famously known as the 'hunger hormone'. However, ample recen...

  15. Hormone therapy and ovarian borderline tumors

    DEFF Research Database (Denmark)

    Mørch, Lina Steinrud; Løkkegaard, Ellen; Andreasen, Anne Helms

    2012-01-01

    Little is known about the influence of postmenopausal hormone therapy on the risk of ovarian borderline tumors. We aimed at assessing the influence of different hormone therapies on this risk.......Little is known about the influence of postmenopausal hormone therapy on the risk of ovarian borderline tumors. We aimed at assessing the influence of different hormone therapies on this risk....

  16. Hg uptake in ureteral obstructions

    International Nuclear Information System (INIS)

    Desgrez, J.P.; Bourguignon, M.; Raynaud, C.; CEA, 91 - Orsay

    1976-01-01

    In the presence of a total obstruction the results obtained with the Hg uptake test, as indeed with other functional tests, inform on the value of the kidney function at the time but have no prognostic value where repair possibilities are concerned. Some preliminary results seem to show however that very soon after the obstacle is removed, by the 10th or 15th day perhaps, quantitative functional tests may once more be used to evaluate the functional prognosis. This would mean that by waiting about two weeks after the disappearance of a total obstruction the Hg uptake test may again be used in all confidence. In order to check this deduction, which is based on slender evidence but which nevertheless has important practical implications, the measurement of the Hg uptake rate during the days following removal of the obstacle appears essential. In long-standing partial obstructions the Hg uptake rate gives an accurate assessment of the functional balance and helps considerably in the choice of therapy [fr

  17. Cellular uptake of metallated cobalamins

    DEFF Research Database (Denmark)

    Tran, Mai Thanh Quynh; Stürup, Stefan; Lambert, Ian Henry

    2016-01-01

    Cellular uptake of vitamin B12-cisplatin conjugates was estimated via detection of their metal constituents (Co, Pt, and Re) by inductively coupled plasma mass spectrometry (ICP-MS). Vitamin B12 (cyano-cob(iii)alamin) and aquo-cob(iii)alamin [Cbl-OH2](+), which differ in the β-axial ligands (CN...

  18. Tumor uptake of radioruthenium compounds

    International Nuclear Information System (INIS)

    Srivastava, S.C.; Richards, P.; Meinken, G.E.; Larson, S.M.; Grunbaum, Z.

    1980-01-01

    The use of ruthenium-97 as a scintigraphic agent, particularly for tumor localization, is investigated. The tumor uptake of ruthenium chloride and ruthenium-labelled transferrin is evaluated and their application as tumor-imagine agents is compared to gallium-67 citrate

  19. Octreotide Uptake in Parathyroid Adenoma

    Directory of Open Access Journals (Sweden)

    Seyhan Karaçavuş

    2012-08-01

    Full Text Available The patient with a history of bone pain and muscle weakness, was thought to have oncogenic osteomalacia as a result of biochemical investigations and directed to Nuclear Medicine Department for a whole-body bone scintigraphy and 111In-octreotide scintigraphy. There was no focal pathologic tracer uptake, but generalized marked increase in skeletal uptake on bone scintigraphy. Octreotide scintigraphy showed accumulation of octreotide in the region of the left lobe of the thyroid gland in the neck. Thereafter, parathyroid scintigraphy was performed with technetium-99m labeled metroxy-isobutyl-isonitryl (99mTc-MIB and MIBI scan demonstrated radiotracer uptake at the same location with octreotide scintigraphy. The patient underwent left inferior parathyroidectomy and histopathology confirmed a parathyroid adenoma. Somatostatin receptor positive parathyroid adenoma may show octreotide uptake. Octreotide scintigraphy may be promising and indicate a possibility of using somatostatin analogues for the medical treatment of somatostatin receptor positive parathyroid tumors. (MIRT 2012;21:77-79

  20. h5-HT1B receptor-mediated constitutive Gαi3-protein activation in stably transfected Chinese hamster ovary cells: an antibody capture assay reveals protean efficacy of 5-HT

    Science.gov (United States)

    Newman-Tancredi, Adrian; Cussac, Didier; Marini, Laetitia; Touzard, Manuelle; Millan, Mark J

    2003-01-01

    Serotonin 5-HT1B receptors couple to G-proteins of the Gi/o family. However, their activation of specific G-protein subtypes is poorly characterised. Using an innovative antibody capture/guanosine-5′-0-(3-[35S]thio)-triphosphate ([35S]GTPγS) binding strategy, we characterised Gαi3 subunit activation by h5-HT1B receptors stably expressed in Chinese hamster ovary (CHO) cells. The agonists, 5-HT, alniditan and BMS181,101, stimulated Gαi3, whereas methiothepin and SB224,289 behaved as inverse agonists. The selective 5-HT1B receptor ligand, S18127, modestly stimulated Gαi3 and reversed the actions of both 5-HT and methiothepin. S18127 (1 μM) also produced parallel, dextral shifts of the 5-HT and methiothepin isotherms. Isotopic dilution experiments ([35S]GTPγS versus GTPγS) revealed high-affinity [35S]GTPγS binding to Gαi3 subunits in the absence of receptor ligands indicating constitutive activity. High-affinity [35S]GTPγS binding was increased 2.8-fold by 5-HT with an increase in the affinity of GTPγS for Gαi3 subunits. In contrast, methiothepin halved the number of high-affinity binding sites and decreased their affinity. h5-HT1B receptor-mediated Gαi3 subunit activation was dependent on the concentration of NaCl. At 300 mM, 5-HT stimulated [35S]GTPγS binding, basal Gαi3 activation was low and methiothepin was inactive. In contrast, at 10 mM NaCl, basal activity was enhanced and the inverse agonist activity of methiothepin was accentuated. Under these conditions, 5-HT decreased Gαi3 activation. In conclusion, at h5-HT1B receptors expressed in CHO cells: (i) inverse agonist induced inhibition of Gαi3, and its reversal by S18127, reveals constitutive activation of this Gα subunit; (ii) constitutive Gαi3 activation can be quantified by isotopic dilution [35S]GTPγS binding and (iii) decreasing NaCl concentrations enhances Gαi3 activation and leads to protean agonist properties of 5-HT: that is a switch to inhibition of Gαi3. PMID:12684263

  1. h5-HT(1B) receptor-mediated constitutive Galphai3-protein activation in stably transfected Chinese hamster ovary cells: an antibody capture assay reveals protean efficacy of 5-HT.

    Science.gov (United States)

    Newman-Tancredi, Adrian; Cussac, Didier; Marini, Laetitia; Touzard, Manuelle; Millan, Mark J

    2003-03-01

    1. Serotonin 5-HT(1B) receptors couple to G-proteins of the Gi/o family. However, their activation of specific G-protein subtypes is poorly characterised. Using an innovative antibody capture/guanosine-5'-0-(3-[(35)S]thio)-triphosphate ([(35)S]GTPgammaS) binding strategy, we characterised Galpha(i3) subunit activation by h5-HT(1B) receptors stably expressed in Chinese hamster ovary (CHO) cells. 2. The agonists, 5-HT, alniditan and BMS181,101, stimulated Galpha(i3), whereas methiothepin and SB224,289 behaved as inverse agonists. The selective 5-HT(1B) receptor ligand, S18127, modestly stimulated Galpha(i3) and reversed the actions of both 5-HT and methiothepin. S18127 (1 micro M) also produced parallel, dextral shifts of the 5-HT and methiothepin isotherms. 3. Isotopic dilution experiments ([(35)S]GTPgammaS versus GTPgammaS) revealed high-affinity [(35)S]GTPgammaS binding to Galpha(i3) subunits in the absence of receptor ligands indicating constitutive activity. High-affinity [(35)S]GTPgammaS binding was increased 2.8-fold by 5-HT with an increase in the affinity of GTPgammaS for Galpha(i3) subunits. In contrast, methiothepin halved the number of high-affinity binding sites and decreased their affinity. 4. h5-HT(1B) receptor-mediated Galpha(i3) subunit activation was dependent on the concentration of NaCl. At 300 mM, 5-HT stimulated [(35)S]GTPgammaS binding, basal Galpha(i3) activation was low and methiothepin was inactive. In contrast, at 10 mM NaCl, basal activity was enhanced and the inverse agonist activity of methiothepin was accentuated. Under these conditions, 5-HT decreased Galpha(i3) activation. 5. In conclusion, at h5-HT(1B) receptors expressed in CHO cells: (i) inverse agonist induced inhibition of Galpha(i3), and its reversal by S18127, reveals constitutive activation of this Galpha subunit; (ii) constitutive Galpha(i3) activation can be quantified by isotopic dilution [(35)S]GTPgammaS binding and (iii) decreasing NaCl concentrations enhances Galpha(i3

  2. Growth Hormone and Endocrinopathies

    Energy Technology Data Exchange (ETDEWEB)

    Kim, K W; Choe, K O; Park, C Y; Lee, H; Son, H Y; Huh, K B; Ryu, K J [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    1979-03-15

    This is an analysis of 39 patients studied at the Yonsei Medical Center from January, 1976 to March 1979. Of these 35 patient were suspected of having hypothalamic insufficiency and subjected to the L-Dopa stimulation test to observe growth hormone secretary function while four acromegaly patient received the glucose loading test and L-Dopa stimulation test. The results are as follows: 1) The basal level of GH in the various disease was as follows: a) The basal level was lower than the control level but was not statistically significant b) In diabetes the mean value tended to higher than the control level but was not significant statistically c) In all four acromegaly patients the GH level was significantly higher than the control level 2) Of 13 patients with diabetes, nine had diabetic retinopathy, and of those nine, six showed increased L-Dopa response. However, of the four non retinopathic DM patients, only one showed increased response to L-Dopa. 3) Two patients out of ten with Sheehan's syndrome responded to L-Dopa stimulation. 4) One Patient of eight with pituitary chromophobe adenoma responded to L-Dopa stimulation. 5) Four acromegaly patients revealed 3 acidophilic adenoma and one chromophobe adenoma histologically. Of patients receiving the L-Dopa stimulation test. Two showed a paradoxical response. Two patients who received the glucose loading test showed suppressed response. 6) Of two craniopharyngioma patients, one showed increased GH response after L-Dopa stimulation. Increased response of GH after L-Dopa stimulation was seen in one two craniopharyngioma patients and also in one of two patients with short structure.

  3. Growth Hormone and Endocrinopathies

    Energy Technology Data Exchange (ETDEWEB)

    Kim, K. W.; Choe, K. O.; Park, C. Y.; Lee, H.; Son, H. Y.; Huh, K. B.; Ryu, K. J. [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    1979-03-15

    This is an analysis of 39 patients studied at the Yonsei Medical Center from January, 1976 to March 1979. Of these 35 patient were suspected of having hypothalamic insufficiency and subjected to the L-Dopa stimulation test to observe growth hormone secretary function while four acromegaly patient received the glucose loading test and L-Dopa stimulation test. The results are as follows: 1) The basal level of GH in the various disease was as follows: a) The basal level was lower than the control level but was not statistically significant b) In diabetes the mean value tended to higher than the control level but was not significant statistically c) In all four acromegaly patients the GH level was significantly higher than the control level 2) Of 13 patients with diabetes, nine had diabetic retinopathy, and of those nine, six showed increased L-Dopa response. However, of the four non retinopathic DM patients, only one showed increased response to L-Dopa. 3) Two patients out of ten with Sheehan's syndrome responded to L-Dopa stimulation. 4) One Patient of eight with pituitary chromophobe adenoma responded to L-Dopa stimulation. 5) Four acromegaly patients revealed 3 acidophilic adenoma and one chromophobe adenoma histologically. Of patients receiving the L-Dopa stimulation test. Two showed a paradoxical response. Two patients who received the glucose loading test showed suppressed response. 6) Of two craniopharyngioma patients, one showed increased GH response after L-Dopa stimulation. Increased response of GH after L-Dopa stimulation was seen in one two craniopharyngioma patients and also in one of two patients with short structure.

  4. Growth Hormone and Endocrinopathies

    International Nuclear Information System (INIS)

    Kim, K. W.; Choe, K. O.; Park, C. Y.; Lee, H.; Son, H. Y.; Huh, K. B.; Ryu, K. J.

    1979-01-01

    This is an analysis of 39 patients studied at the Yonsei Medical Center from January, 1976 to March 1979. Of these 35 patient were suspected of having hypothalamic insufficiency and subjected to the L-Dopa stimulation test to observe growth hormone secretary function while four acromegaly patient received the glucose loading test and L-Dopa stimulation test. The results are as follows: 1) The basal level of GH in the various disease was as follows: a) The basal level was lower than the control level but was not statistically significant b) In diabetes the mean value tended to higher than the control level but was not significant statistically c) In all four acromegaly patients the GH level was significantly higher than the control level 2) Of 13 patients with diabetes, nine had diabetic retinopathy, and of those nine, six showed increased L-Dopa response. However, of the four non retinopathic DM patients, only one showed increased response to L-Dopa. 3) Two patients out of ten with Sheehan's syndrome responded to L-Dopa stimulation. 4) One Patient of eight with pituitary chromophobe adenoma responded to L-Dopa stimulation. 5) Four acromegaly patients revealed 3 acidophilic adenoma and one chromophobe adenoma histologically. Of patients receiving the L-Dopa stimulation test. Two showed a paradoxical response. Two patients who received the glucose loading test showed suppressed response. 6) Of two craniopharyngioma patients, one showed increased GH response after L-Dopa stimulation. Increased response of GH after L-Dopa stimulation was seen in one two craniopharyngioma patients and also in one of two patients with short structure.

  5. Ocean carbon uptake and storage

    International Nuclear Information System (INIS)

    Tilbrook, Bronte

    2007-01-01

    Full text: The ocean contains about 95% of the carbon in the atmosphere, ocean and land biosphere system, and is of fundamental importance in regulating atmospheric carbon dioxide concentrations. In the 1990s an international research effort involving Australia was established to determine the uptake and storage of anthropogenic C02 for all major ocean basins. The research showed that about 118 of the 244 + 20 billion tons of the anthropogenic carbon emitted through fossil fuel burning and cement production has been stored in the ocean since preindustrial times, thus helping reduce the rate of increase in atmospheric C02. The research also showed the terrestrial biosphere has been a small net source of C02 (39 ± 28 billion tons carbon) to the atmosphere over the same period. About 60% of the total ocean inventory of the anthropogenic C02 was found in the Southern Hemisphere, with most in the 30 0 S to 50 0 S latitude band. This mid-latitude band is where surface waters are subducted as Mode and Intermediate waters, which is a major pathway controlling ocean C02 uptake. High storage (23% of the total) also occurs in the North Atlantic, associated with deep water formation in that basin. The ocean uptake and storage is expected to increase in the coming decades as atmospheric C02 concentrations rise. However, a number of feedback mechanisms associated with surface warming, changes in circulation, and biological effects are likely to impact on the uptake capacity. The accumulation or storage-of the C02 in the ocean is also the major driver of ocean acidification with potential to disrupt marine ecosystems. This talk will describe the current understanding of the ocean C02 uptake and storage and a new international research strategy to detect how the ocean uptake and storage will evolve on interannual through decadal scales. Understanding the ocean response to increasing atmospheric C02 will be a key element in managing future C02 increases and establishing

  6. Gastrointestinal hormone research - with a Scandinavian annotation

    DEFF Research Database (Denmark)

    Rehfeld, Jens F

    2015-01-01

    Gastrointestinal hormones are peptides released from neuroendocrine cells in the digestive tract. More than 30 hormone genes are currently known to be expressed in the gut, which makes it the largest hormone-producing organ in the body. Modern biology makes it feasible to conceive the hormones...... as a blood-borne hormone, a neurotransmitter, a local growth factor or a fertility factor. The targets of gastrointestinal hormones are specific G-protein-coupled receptors that are expressed in the cell membranes also outside the digestive tract. Thus, gut hormones not only regulate digestive functions...

  7. FDG uptake in the stomach

    International Nuclear Information System (INIS)

    Yun, M. J.; Cho, H. J.; Cho, E. H.; Kim, T. S.; Kang, W. J.; Lee, J. D.

    2007-01-01

    This study was performed to evaluate histopathologic features of advanced gastric cancer (AGC) to predict FDG uptake on PET. 153 patients(102 men; mean age, 55 y) were diagnosed with AGC by surgery were included in this study. PET images were evaluated by visual and semi-quantitative analysis of FDG uptake in primary tumors. Primary tumors size were measured and divided according to Borrmann classification. Tumor histology was classified under WHO classification, depth of invasion and Iymphovascular invasion. The tumors were also grouped by high cellular(cellularity = 50%) and low cellular group (<50%). Microscopic growth type was based on Lauren classification. Stromal fibrosis degree and inflammatory cell infiltration amount was graded as low(none∼mild), or high(moderate∼severe). Lymph node metastases was assessed in all patients. Statistical analyses were performed to evaluate differences in SUV as to histopathologic factors. Of the 153 patients, 21 patients(14%) had primary tumor invisible on initial whole body images. After water ingestion, the tumors became visible in 15 of the 21 patients due to disappearance of physiologic stomach uptake. Polypoid or ulcerofungating tumors, high cellularity, intestinal growth pattern, and larger tumors significantly predicted increased tumor SUVs. Well or moderately differentiated adenocarcinoma tended to show high cellularity and intestinal growth pattern. Poorly differentiated adenocarcinoma had diverse spectrum of histopathology. Signet ring cell carcinomas were mostly ulceroinfiltrative or diffusely infiltrative in macroscopic type and diffuse in microscopic tumor growth. Mucinous adenocarcinomas were mostly low in cellularity. FDG uptake patterns are useful in representing histopathologic characteristics of the entire tumor in gastric cancers. The degree of FDG uptake depends on tumor size, macroscopic type, cellularity, and microscopic growth pattern and it shows no association with well known important prognostic

  8. Sex Hormones and Their Receptors Regulate Liver Energy Homeostasis

    Directory of Open Access Journals (Sweden)

    Minqian Shen

    2015-01-01

    Full Text Available The liver is one of the most essential organs involved in the regulation of energy homeostasis. Hepatic steatosis, a major manifestation of metabolic syndrome, is associated with imbalance between lipid formation and breakdown, glucose production and catabolism, and cholesterol synthesis and secretion. Epidemiological studies show sex difference in the prevalence in fatty liver disease and suggest that sex hormones may play vital roles in regulating hepatic steatosis. In this review, we summarize current literature and discuss the role of estrogens and androgens and the mechanisms through which estrogen receptors and androgen receptors regulate lipid and glucose metabolism in the liver. In females, estradiol regulates liver metabolism via estrogen receptors by decreasing lipogenesis, gluconeogenesis, and fatty acid uptake, while enhancing lipolysis, cholesterol secretion, and glucose catabolism. In males, testosterone works via androgen receptors to increase insulin receptor expression and glycogen synthesis, decrease glucose uptake and lipogenesis, and promote cholesterol storage in the liver. These recent integrated concepts suggest that sex hormone receptors could be potential promising targets for the prevention of hepatic steatosis.

  9. Diffusely increased uptake in the skull in normal bone scans

    International Nuclear Information System (INIS)

    Suematsu, Toru; Yoshida, Shoji; Motohara, Tomofumi; Fujiwara, Hirofumi; Nishii, Hironori; Komiyama, Toyozo; Yanase, Masakazu; Mizutani, Masahiro

    1992-01-01

    Diffusely increased skull uptake (a hot skull) is often seen in patients with bone metastases and metabolic disease. This finding is also, however, noticed in normal bone scans of aged women. To determine whether the hot skull could be considered a normal variant in elderly women and is associated to menopause, we studied 282 normal bone scans (166 women and 116 men without metabolic and hormonal disease; age range 11 to 84 yr). We divided the patients into eight age groups--ages 10-19, 20-29, 30-39, 40-49, 50-59, 60-69, 70-79, and 80-89 yrs. Measurements of skull uptake were obtained from anterior total body views using contrast-to-noise ratio (CNR). CNR for the skull was calculated using an equation. The sex dependent difference in skull uptake began to develop in the age group 30-39 yrs (p<0.05). The skull showed greater activity in women than in men for age groups from 30-39 to 80-89 yrs. In the age groups 50-59 and 60-69, the difference was particularly large (p<0.001). For women, the 50-59 yr age group had a significantly higher CNR than the 40-49 yr (p<0.01), 30-39 yr (p<0.05), and 20-29 yr age group (p<0.05). On the other hand, there was no significant difference between the 20-29 yr, 30-39 yr and 40-49 yr age groups. For men, the skull uptake was virtually unchanged with age. Our data strongly suggested that the hot skull in normal bone scan is related to menopausal estrogen deficiency. One should not necessarily regard it abnormal that elderly women suffer hot skull. (J.P.N.)

  10. Thyroid uptake of {sup 67}Ga-citrate is associated with thyroid autoimmunity and hypothyroidism in patients with sarcoidosis

    Energy Technology Data Exchange (ETDEWEB)

    Antonelli, Alessandro; Fallahi, Poupak; Ferrari, Silvia Martina; Ferrannini, Ele [University of Pisa and CNR Institute of Clinical Physiology, Metabolism Unit, Department of Internal Medicine, Pisa (Italy); Fazzi, Piera [University of Pisa, Respiratory Pathophysiology Section, Cardiac and Thoracic Department, Pisa (Italy); Grosso, Mariano; Boni, Giuseppe; Mariani, Giuliano [University of Pisa, Regional Center of Nuclear Medicine, Medical School, Pisa (Italy)

    2009-01-15

    To evaluate the association of gallium-67 ({sup 67}Ga)-citrate thyroid uptake with the presence of thyroid disorders in patients with sarcoidosis (S patients). Eighty-four S patients were evaluated by a complete thyroid work-up (neck ultrasound, circulating thyroid hormones and anti-thyroid antibodies, fine-needle aspiration). In S patients with {sup 67}Ga thyroid uptake (respect those without): serum thyroid-stimulating hormone, the titre of anti-thyroid peroxidase (AbTPO) and/or anti-thyroglobulin antibodies (AbTg), and the prevalence of S patients with hypothyroidism or with positive AbTg or AbTPO was significantly higher; a thyroid hypoechoic pattern was more frequent. The prevalence of thyroid nodules was not significantly different between the two groups. Two cases of papillary thyroid cancer were observed in S patients without {sup 67}Ga thyroid uptake, whilst no case in those with {sup 67}Ga thyroid uptake. {sup 67}Ga thyroid uptake is associated with the presence of aggressive autoimmune thyroiditis and hypothyroidism in S patients; thyroid function and ultrasonography should be performed in the presence of {sup 67}Ga thyroid uptake. (orig.)

  11. Thyroid uptake of 67Ga-citrate is associated with thyroid autoimmunity and hypothyroidism in patients with sarcoidosis

    International Nuclear Information System (INIS)

    Antonelli, Alessandro; Fallahi, Poupak; Ferrari, Silvia Martina; Ferrannini, Ele; Fazzi, Piera; Grosso, Mariano; Boni, Giuseppe; Mariani, Giuliano

    2009-01-01

    To evaluate the association of gallium-67 ( 67 Ga)-citrate thyroid uptake with the presence of thyroid disorders in patients with sarcoidosis (S patients). Eighty-four S patients were evaluated by a complete thyroid work-up (neck ultrasound, circulating thyroid hormones and anti-thyroid antibodies, fine-needle aspiration). In S patients with 67 Ga thyroid uptake (respect those without): serum thyroid-stimulating hormone, the titre of anti-thyroid peroxidase (AbTPO) and/or anti-thyroglobulin antibodies (AbTg), and the prevalence of S patients with hypothyroidism or with positive AbTg or AbTPO was significantly higher; a thyroid hypoechoic pattern was more frequent. The prevalence of thyroid nodules was not significantly different between the two groups. Two cases of papillary thyroid cancer were observed in S patients without 67 Ga thyroid uptake, whilst no case in those with 67 Ga thyroid uptake. 67 Ga thyroid uptake is associated with the presence of aggressive autoimmune thyroiditis and hypothyroidism in S patients; thyroid function and ultrasonography should be performed in the presence of 67 Ga thyroid uptake. (orig.)

  12. Association of primary tumour FDG uptake with clinical, histopathological and molecular characteristics in breast cancer patients scheduled for neoadjuvant chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Koolen, B.B.; Aukema, T.S. [Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Nuclear Medicine, Amsterdam (Netherlands); Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Surgical Oncology, Amsterdam (Netherlands); Vrancken Peeters, M.J.T.F.D.; Rutgers, E.J.T. [Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Surgical Oncology, Amsterdam (Netherlands); Wesseling, J.; Lips, E.H. [Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Pathology and Experimental Therapy, Amsterdam (Netherlands); Vogel, W.V.; Valdes Olmos, R.A. [Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Nuclear Medicine, Amsterdam (Netherlands); Werkhoven, E. van [Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Biometrics, Amsterdam (Netherlands); Gilhuijs, K.G.A. [Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Radiology, Amsterdam (Netherlands); University Medical Centre Utrecht, Department of Radiology, Utrecht (Netherlands); Rodenhuis, S. [Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Medical Oncology, Amsterdam (Netherlands)

    2012-12-15

    The aim of this study was to evaluate the association of primary tumour {sup 18}F-fluorodeoxyglucose (FDG) uptake with clinical, histopathological and molecular characteristics of breast cancer patients scheduled for neoadjuvant chemotherapy. Second, we wished to establish for which patients pretreatment positron emission tomography (PET)/CT could safely be omitted because of low FDG uptake. PET/CT was performed in 214 primary stage II or III breast cancer patients in the prone position with hanging breasts. Tumour FDG uptake was qualitatively evaluated to determine the possibility of response monitoring with PET/CT and was quantitatively assessed using maximum standardized uptake values (SUV{sub max}). FDG uptake was compared with age, TNM stage, histology, hormone and human epidermal growth factor receptor 2 status, grade, Ki-67 and molecular subtype in univariable and multivariable analyses. In 203 tumours (95 %) FDG uptake was considered sufficient for response monitoring. No subgroup of patients with consistently low tumour FDG uptake could be identified. In a univariable analysis, SUV{sub max} was significantly higher in patients with distant metastases at staging examination, non-lobular carcinomas, tumours with negative hormone receptors, triple negative tumours, grade 3 tumours, and in tumours with a high proliferation index (Ki-67 expression). After multiple linear regression analysis, triple negative and grade 3 tumours were significantly associated with a higher SUV{sub max}. Primary tumour FDG uptake in breast cancer patients scheduled for neoadjuvant chemotherapy is significantly higher in tumours with prognostically unfavourable characteristics. Based on tumour characteristics associated with low tumour FDG uptake, this study was unable to identify a subgroup of patients unlikely to benefit from pretreatment PET/CT. (orig.)

  13. Wheat seed enhancement by vitamin and hormonal priming

    International Nuclear Information System (INIS)

    Khan, M.B.; Gurchani, M.A.; Hussain, M.

    2011-01-01

    Seed priming has proven beneficial in many important agricultural crops. The present study was conducted to explore the role (if any) of hormonal and vitamin seed priming to improve the germination, seedling emergence, early seedling establishment, electrolyte leakage and nutrients uptake in wheat seedlings. The wheat seeds were soaked for 48 hours in aerated solution of salicylic acid, ascorbic acid, kinetin and GA3 with 20 ppm concentration of each solution, whereas untreated seeds were taken as control. Seed priming with ascorbic acid resulted in maximum final germination and emergence percentage (FGP and FEP), radical and plumule length, root and shoot length, number of secondary roots, root shoot ratio, root dry weight, shoot dry weight and seedling dry weight compared to control (untreated seeds). Minimum mean germination and emergence time (MGT and MET) was recorded in seeds primed with kinetin and GA3. While in case of biochemical attributes, seedling potassium contents were decreased by hormonal seed priming while total soluble sugars were increased by salicylic acid and ascorbic acid seed priming. Hormonal seed priming had non-significant effect on phosphorus seedling contents. Untreated (Control) seeds showed maximum electrical conductivity at 0.5, 1, 2, 6, 12 and 24 h after inbibition than primed seeds against the minimum electrical conductivity that was recorded in seeds primed with salicylic acid and ascorbic acid. In conclusion, the wheat seeds primed with 20 ppm solution of ascorbic acid may be used for wheat seed invigoration. (author)

  14. Hormonal Approaches to Male contraception

    Science.gov (United States)

    Wang, Christina; Swerdloff, Ronald S.

    2010-01-01

    Purpose of review Condoms and vasectomy are male controlled family planning methods but suffer from limitations in compliance (condoms) and limited reversibility (vasectomy); thus many couples desire other options. Hormonal male contraceptive methods have undergone extensive clinical trials in healthy men and shown to be efficacious, reversible and appear to be safe. Recent Findings The success rate of male hormonal contraception using injectable testosterone alone is high and comparable to methods for women. Addition of progestins to androgens improved the rate of suppression of spermatogenesis. Supported by government or non-government organizations, current studies aim to find the best combination of testosterone and progestins for effective spermatogenesis suppression and to explore other delivery methods for these hormones. Translation of these advances to widespread use in the developed world will need the manufacturing and marketing skills of the pharmaceutical industry. Availability of male contraceptives to the developing world may require commitments of governmental and non-governmental agencies. In a time when imbalance of basic resources and population needs are obvious, this may prove to be a very wise investment. Summary Male hormonal contraception is efficacious, reversible and safe for the target population of younger men in stable relationships. Suppression of spermatogenesis is achieved with a combination of an androgen and a progestin. Partnership with industry will accelerate the marketing of a male hormonal contraceptive. Research is ongoing on selective androgen and progesterone receptor modulators that suppress spermatogenesis, minimize potential adverse events while retaining the androgenic actions. PMID:20808223

  15. Hormone therapy and ovarian cancer

    DEFF Research Database (Denmark)

    Mørch, Lina Steinrud; Løkkegaard, Ellen; Andreasen, Anne Helms

    2009-01-01

    CONTEXT: Studies have suggested an increased risk of ovarian cancer among women taking postmenopausal hormone therapy. Data are sparse on the differential effects of formulations, regimens, and routes of administration. OBJECTIVE: To assess risk of ovarian cancer in perimenopausal and postmenopau......CONTEXT: Studies have suggested an increased risk of ovarian cancer among women taking postmenopausal hormone therapy. Data are sparse on the differential effects of formulations, regimens, and routes of administration. OBJECTIVE: To assess risk of ovarian cancer in perimenopausal...... and postmenopausal women receiving different hormone therapies. DESIGN AND SETTING: Nationwide prospective cohort study including all Danish women aged 50 through 79 years from 1995 through 2005 through individual linkage to Danish national registers. Redeemed prescription data from the National Register...... bands included hormone exposures as time-dependent covariates. PARTICIPANTS: A total of 909,946 women without hormone-sensitive cancer or bilateral oophorectomy. MAIN OUTCOME MEASURE: Ovarian cancer. RESULTS: In an average of 8.0 years of follow-up (7.3 million women-years), 3068 incident ovarian...

  16. Incidental Diagnosis of Carcinoma of the Bladder Due to Uptake of 99mTc-MDP

    International Nuclear Information System (INIS)

    Damle, Nishikant A; Pandey, Dinesh Chand; Gautam, Awadhesh Kumar; Subbarao, Kiran; Singh, Prabhjot; Mishra, Rohini; Das, Nitendra Lal; Pandey, Dinesh Chand; Gautam, Awadhesh Kumar

    2012-01-01

    A bone scan was per-formed using 740 MBq (29 mCi) 99 mTc-MDP. Whole-body planar images were acquired 3 h after injection (Fig. 1). Soft tissue uptake of 99 mTc-MDP is described in various benign and malignant conditions. It is known to accumulate in adenocarcinoma of lung, primary breast cancer, and colonic carcinoma among others. The postulated causes of 99 mTc-MDP uptake in extraosseous neoplasms are numerous and include tumor vascularity, inflammation, local pH factors, altered calcium metabolism, hormonal influences and cell wall damage. Our case shows that TCC of the bladder was incidentally diagnosed due to MDP uptake in multiple bladder polyps detected on a bone scan done for low backache in an 80-year-old man

  17. Radioimmunological and clinical studies with luteinizing hormone releasing hormone (LRH)

    International Nuclear Information System (INIS)

    Dahlen, H.G.

    1986-01-01

    Radioimmunoassay for Luteinizing Hormone Releasing Hormone (LRH) has been established, tested and applied. Optimal conditions for the performance with regards to incubation time, incubation temperature, concentration of antiserum and radiolabelled LRH have been established. The specificity of the LRH immunoassay was investigated. Problems with direct measurement of LRH in plasmas of radioimmunoassay are encountered. The LRH distribution in various tissues of the rat are investigated. By means of a system for continuous monitoring of LH and FSH in women the lowest effective dose of LRH causing a significant release of LH and FSH could be established. (Auth.)

  18. Increased cellular uptake of lauryl gallate loaded in superparamagnetic poly(methyl methacrylate) nanoparticles due to surface modification with folic acid.

    Science.gov (United States)

    Feuser, Paulo Emilio; Arévalo, Juan Marcelo Carpio; Junior, Enio Lima; Rossi, Gustavo Rodrigues; da Silva Trindade, Edvaldo; Rocha, Maria Eliane Merlin; Jacques, Amanda Virtuoso; Ricci-Júnior, Eduardo; Santos-Silva, Maria Claudia; Sayer, Claudia; de Araújo, Pedro H Hermes

    2016-12-01

    Lauryl gallate loaded in superparamagnetic poly(methyl methacrylate) nanoparticles surface modified with folic acid were synthesized by miniemulsion polymerization in just one step. In vitro biocompatibility and cytotoxicity assays on L929 (murine fibroblast), human red blood, and HeLa (uterine colon cancer) cells were performed. The effect of folic acid at the nanoparticles surface was evaluated through cellular uptake assays in HeLa cells. Results showed that the presence of folic acid did not affect substantially the polymer particle size (~120 nm), the superparamagnetic behavior, the encapsulation efficiency of lauryl gallate (~87 %), the Zeta potential (~38 mV) of the polymeric nanoparticles or the release profile of lauryl gallate. The release profile of lauryl gallate from superparamagnetic poly(methyl methacrylate) nanoparticles presented an initial burst effect (0-1 h) followed by a slow and sustained release, indicating a biphasic release system. Lauryl gallate loaded in superparamagnetic poly(methyl methacrylate) nanoparticles with folic acid did not present cytotoxicity effects on L929 and human red blood cells. However, free lauryl gallate presented significant cytotoxic effects on L929 and human red blood cells at all tested concentrations. The presence of folic acid increased the cytotoxicity of lauryl gallate loaded in nanoparticles on HeLa cells due to a higher cellular uptake when HeLa cells were incubated at 37 °C. On the other hand, when the nanoparticles were incubated at low temperature (4 °C) cellular uptake was not observed, suggesting that the uptake occurred by folate receptor mediated energy-dependent endocytosis. Based on presented results our work suggests that this carrier system can be an excellent alternative in targeted drug delivery by folate receptor.

  19. Arsenic uptake in bacterial calcite

    Science.gov (United States)

    Catelani, Tiziano; Perito, Brunella; Bellucci, Francesco; Lee, Sang Soo; Fenter, Paul; Newville, Matthew; Rimondi, Valentina; Pratesi, Giovanni; Costagliola, Pilario

    2018-02-01

    Bio-mediated processes for arsenic (As) uptake in calcite were investigated by means of X-ray Diffraction (XRD) and X-ray Absorption Spectroscopy (XAS) coupled with X-ray Fluorescence measurements. The environmental bacterial strain Bacillus licheniformis BD5, sampled at the Bullicame Hot Springs (Viterbo, Central Italy), was used to synthesize calcite from As-enriched growth media. Both liquid and solid cultures were applied to simulate planktonic and biofilm community environments, respectively. Bacterial calcite samples cultured in liquid media had an As enrichment factor (Kd) 50 times higher than that from solid media. The XRD analysis revealed an elongation of the crystal lattice along the c axis (by 0.03 Å) for biogenic calcite, which likely resulted from the substitution of larger arsenate for carbonate in the crystal. The XAS data also showed a clear difference in the oxidation state of sorbed As between bacterial and abiotic calcite. Abiotic chemical processes yielded predominantly As(V) uptake whereas bacterial precipitation processes led to the uptake of both As(III) and As(V). The presence of As(III) in bacterial calcite is proposed to result from subsequent reduction of arsenate to arsenite by bacterial activities. To the best of our knowledge, this is the first experimental observation of the incorporation of As(III) in the calcite crystal lattice, revealing a critical role of biochemical processes for the As cycling in nature.

  20. Arsenic uptake in bacterial calcite

    Energy Technology Data Exchange (ETDEWEB)

    Catelani, Tiziano; Perito, Brunella; Bellucci, Francesco; Lee, Sang Soo; Fenter, Paul; Newville, Matthew G.; Rimondi, Valentina; Pratesi, Giovanni; Costagliola, Pilario

    2018-02-01

    Bio-mediated processes for arsenic (As) uptake in calcite were investigated by means of X-ray Diffraction (XRD) and Xray Absorption Spectroscopy (XAS) coupled with X-ray Fluorescence measurements. The environmental bacterial strain Bacillus licheniformis BD5, sampled at the Bullicame Hot Springs (Viterbo, Central Italy), was used to synthesize calcite from As-enriched growth media. Both liquid and solid cultures were applied to simulate planktonic and biofilm community environments, respectively. Bacterial calcite samples cultured in liquid media had an As enrichment factor (Kd) 50 times higher than that from solid media. The XRD analysis revealed an elongation of the crystal lattice along the c axis (by 0.03Å) for biogenic calcite, which likely resulted from the substitution of larger arsenate for carbonate in the crystal. The XAS data also showed a clear difference in the oxidation state of sorbed As between bacterial and abiotic calcite. Abiotic chemical processes yielded predominantly As(V) uptake whereas bacterial precipitation processes led to the uptake of both As(III) and As(V). The presence of As(III) in bacterial calcite is proposed to result from subsequent reduction of arsenate to arsenite by bacterial activities. To the best of our knowledge, this is the first experimental observation of the incorporation of As(III) in the calcite crystal lattice, revealing a critical role of biochemical processes for the As cycling in nature.

  1. Electrochemical biosensors for hormone analyses.

    Science.gov (United States)

    Bahadır, Elif Burcu; Sezgintürk, Mustafa Kemal

    2015-06-15

    Electrochemical biosensors have a unique place in determination of hormones due to simplicity, sensitivity, portability and ease of operation. Unlike chromatographic techniques, electrochemical techniques used do not require pre-treatment. Electrochemical biosensors are based on amperometric, potentiometric, impedimetric, and conductometric principle. Amperometric technique is a commonly used one. Although electrochemical biosensors offer a great selectivity and sensitivity for early clinical analysis, the poor reproducible results, difficult regeneration steps remain primary challenges to the commercialization of these biosensors. This review summarizes electrochemical (amperometric, potentiometric, impedimetric and conductometric) biosensors for hormone detection for the first time in the literature. After a brief description of the hormones, the immobilization steps and analytical performance of these biosensors are summarized. Linear ranges, LODs, reproducibilities, regenerations of developed biosensors are compared. Future outlooks in this area are also discussed. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. 99mTc-MDP bone uptake in secondary hyperparathyroidism: comparison among mandible, cranium, radius and femur

    International Nuclear Information System (INIS)

    Boasquevisque, Edson; Silva, Jorge Wagner Esteves da; Bernardo, Vanessa V. de Albuquerque; Macedo, Sara Mello Santana de; Boasquevisque, Camila S.

    2008-01-01

    Full text: Objective: Evaluating bone involvement in secondary hyperparathyroidism (SHPT) by 99m Tc-MDP uptake in the mandible, cranium, radius and femur and with data correlation with PTHi serum (Intact Parathyroid Hormone). Materials and Methods: In a prospective study of 54 patients with SHPT due to chronic renal disease and 15 normal individuals (control group), all patients had elevated serum PTHi, concentration and positive 99m Tc-MDP bone scintigraphy. Bone uptake measurements were carried out drawing regions-of-interest (ROI) on the mandible, posterior cranium, distal radius and proximal femur. Additionally, soft tissue uptake was measured with one region-of-interest on the internal tight soft tissue (BG). The ROI-BG ratio used as the index of normalized bone uptake. Results: The uptake differences from SHPT and control groups mainly for mandible (p = 0,001) and cranium (p = 0,002) were statistically significant, even when the SHPT groups were separated according to serum PTHi levels. There was increased bone uptake with the increased levels of PTHi serum. All of the mandibles of the SHPT patients were abnormal with 33% having focal lesions. Conclusions: The bone uptake in SHPT group was abnormal in all areas evaluated, with high uptake of 99m Tc-MDP correlated to the increase of PTHi serum concentration. (author)

  3. 99mTc-MDP bone uptake in secondary hyperparathyroidism. Comparison of the mandible, cranium, radius, and femur

    International Nuclear Information System (INIS)

    Boasquevisque, Edson; Mandarim-de-Lacerda, Carlos A.; Silva, Jorge Wagner Esteves da; Albuquerque Bernardo, V.V. de; Macedo, S. Mello Santana de; Oliveira, Andre Ribeiro Nogueira de; Pires Kasai, Erika Tami; Boasquevisque, Camila S.

    2008-01-01

    The objective of this study to evaluate the bone involvement of the mandible, cranium, radius, and femur in secondary hyperparathyroidism (SHPT) using 99m Tc-methylene diphosphonate sodium (MDP) uptake correlated with the serum intact parathyroid hormone (PTHi). In a prospective study of 54 patients with SHPT due to chronic renal disease and 15 normal individuals (control group), all patients had elevated serum PTHi and 99m Tc-MDP bone scintigraphy. Bone uptake was measured in regions of interest (ROIs) in the mandible posterior cranium, distal radius, and proximal femur. In addition, soft tissue uptake was measured in one ROI in the soft tissues of the medial thigh (BG). The ROI-BG ratio was used as an index of the normalized bone uptake. The uptake differences in the SHPT and control groups were statistically significant for the mandible (P=0.001) and cranium (P=0.002). When the SHPT group was subclassified according to serum PTHi levels, the bone uptake increased with the serum PTHi level. All mandibles of the patients with SHPT were abnormal, and 33% had focal lesions. The bone uptake in the SHPT group was abnormal in all areas evaluated, and a high uptake of 99m Tc-MDP was correlated with an increased serum PTHi. (author)

  4. Plant uptake of dual-labeled organic N biased by inorganic C uptake

    DEFF Research Database (Denmark)

    Rasmussen, Jim; Sauheitl, Leopold; Eriksen, Jørgen

    2010-01-01

    glycine or CO2-3 , but found no differences in uptake rates between these C-sources. The uptake of inorganic C to the shoot tissue was higher for maize grown in full light compared to shading, which indicates a passive uptake of inorganic C with water. We conclude that uptake of inorganic C produced...

  5. Some theoretical aspects of hormone receptor determination

    International Nuclear Information System (INIS)

    Sluiter, W.J.

    1981-01-01

    Suitable antisera for determination of hormone receptors are not available for the majority of hormone receptors. Therefore, the determination of hormone receptors is mostly performed in terms of binding capacity for the appropriate hormone, using radioactive hormone labels. Some theoretical aspects of such a receptor determination are discussed including the length of incubation (total or unoccupied receptor concentration), single point or multiple point (Scatchard) analysis (regarding the influence of other specific binders), the correction procedure for non-specific binding and the influence of the circulating hormone level. (Auth.)

  6. Advances in male hormonal contraception.

    Science.gov (United States)

    Costantino, Antonietta; Gava, Giulia; Berra, Marta; Meriggiola Maria, Cristina

    2014-11-01

    Contraception is a basic human right for its role on health, quality of life and wellbeing of the woman and of the society as a whole. Since the introduction of female hormonal contraception the responsibility of family planning has always been with women. Currently there are only a few contraceptive methods available for men, but recently, men have become more interested in supporting their partners actively. Over the last few decades different trials have been performed providing important advances in the development of a safe and effective hormonal contraceptive for men. This paper summarizes some of the most recent trials.

  7. Advances in male hormonal contraception

    Directory of Open Access Journals (Sweden)

    Costantino Antonietta

    2014-01-01

    Full Text Available Contraception is a basic human right for its role on health, quality of life and wellbeing of the woman and of the society as a whole. Since the introduction of female hormonal contraception the responsibility of family planning has always been with women. Currently there are only a few contraceptive methods available for men, but recently, men have become more interested in supporting their partners actively. Over the last few decades different trials have been performed providing important advances in the development of a safe and effective hormonal contraceptive for men. This paper summarizes some of the most recent trials.

  8. Hormonal interaction in diabetic pregnancy

    International Nuclear Information System (INIS)

    Hafiez, A.R.A.; Abdel-Hafez, M.A.; Osman, E.A.; Ibrahim, M.S.

    1984-01-01

    Serum glucose, human placental lactogen (HPL), prolactin (PRL), estradiol (E 2 ), progesterone (P), cortisol and human growth hormone (HGH) were determined in nondiabetic (19 cases) and diabetic (19 cases) pregnant women during the 32nd and 36th week of gestation. Significant elevation of HPL, PRL, HGH and cortisol was found in the diabetic pregnant women during the 32nd week while E 2 and P were not significantly changed from the corresponding levels in the nondiabetic group. One can conclude that the changes in the hormonal pattern during gestation may induce carbohydrate intolerance observed in diabetic pregnancies. (author)

  9. Hormonal contraception, thrombosis and age

    DEFF Research Database (Denmark)

    Lidegaard, Øjvind

    2014-01-01

    : First choice in women below 35 years should be a combined low-risk pill, that is, with a second-generation progestin, with the lowest compliable dose of estrogen. Young women with risk factors of thrombosis such as age above 35 years, genetic predispositions, adiposity, polycystic ovary syndrome......INTRODUCTION: This paper reviews the risk of thrombosis with use of different types of hormonal contraception in women of different ages. AREAS COVERED: Combined hormonal contraceptives with desogestrel, gestodene, drospirenone or cyproterone acetate (high-risk products) confer a sixfold increased...

  10. Hormonal Changes and Sexual Dysfunction.

    Science.gov (United States)

    Zhou, Eric S; Frederick, Natasha N; Bober, Sharon L

    2017-11-01

    Sexual dysfunction is a common concern for many patients with cancer after treatment. Hormonal changes as a result of cancer-directed therapy can affect both male and female sexual health. This has the potential to significantly impact patients' quality of life, but is underreported and undertreated in the oncology setting. This review discusses commonly reported sexual issues and the role that hormonal changes play in this dysfunction. Although medical and psychosocial intervention strategies exist, there is a clear need for further research to formally develop programming that can assist people whose sexual health has been impacted by cancer treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Luteinizing hormone in testicular descent

    DEFF Research Database (Denmark)

    Toppari, Jorma; Kaleva, Marko M; Virtanen, Helena E

    2007-01-01

    alone is not sufficient for normal testicular descent. The regulation of androgen production is influenced both by placental human chorionic gonadotropin (hCG) and pituitary luteinizing hormone (LH). There is evidence that the longer pregnancy continues, the more important role pituitary LH may have....... Insulin-like hormone-3 (INSL3) is suggested to be the main regulator of gubernacular development and therefore an apparent regulator of testicular descent. INSL3 production is also related to LH, and reduced INSL3 action is a possible cause for cryptorchidism. Cryptorchid boys have normal testosterone...

  12. Analysis of the factors associated with Tc-99m pertechnetate uptake in thyrotoxicosis and Graves' disease

    International Nuclear Information System (INIS)

    Kidokoro-kunii, Yo; Emoto, Naoya; Cho, Keiichi; Oikawa, Shinichi

    2006-01-01

    To determine the factors associated with 20 minute Tc-99m pertechnetate thyroid uptake, we examined all patients in whom thyrotoxicosis was diagnosed at Chiba-Hokusoh Hospital, Nippon Medical School from 2001 April through 2003 March. Patients with thyrotoxicosis diagnosed during this period were 57 with Graves' disease (76%), 11 with transient hyperthyroxinemia (TH) (14.7%), and 7 with subacute thyroiditis (SAT) (9.3%). The uptake of Tc-99m ranged from 0.97% to 40.1% in Graves' disease and from 0.15% to 0.8% in TH. Although TH may include spontaneous resolution of Graves' disease as well as painless thyroiditis, no treatment was necessary for these patients. Uptake in all patients with SAT was less than 0.5%. There were significant correlations between the level of Tc-99m uptake and the levels of free triiodothyronine (fT3), free thyroxine (fT4), thyroid-stimulating hormone (TSH)-binding inhibitory immunoglobulin (TBII), and thyroid stimulating antibody (TSAb) in patients with Graves' disease. Older patients with Graves' disease showed lower uptake than did younger patients. Both Tc-99m pertechnetate uptake and TBII levels, but not fT3, fT4 or TSAb levels, at the beginning of antithyroid drug treatment correlated significantly with the duration of treatment until the daily dose of methimazole reached 5 mg. These data suggest that Tc-99m pertechnetate uptake reflects the severity of Graves' disease and its response to the medical treatment and that antithyroid drug therapy is not necessary when the uptake is less than 0.9%. (author)

  13. Interactions between the thyroid hormones and the hormones of the growth hormone axis.

    Science.gov (United States)

    Laron, Zvi

    2003-12-01

    The normal secretion and action of the thyroid hormones and the hormones of the GH/IGF-I (growth hormone/ insulin-like growth factor I) axis are interdependent. Their interactions often differ in man from animal studies in rodents and sheep. Thus neonates with congenital hypothyroidism are of normal length in humans but IUGR (intrauterine growth retardation) in sheep. Postnatally normal GH/IGF-I secretion and action depends on an euthyroid state. Present knowledge on the interactions between the two axes is reviewed in states of hypo- and hyperthyroidism, states of GH/IGF-I deprivation and hypersecretion, as well as the relationship between IGF-I and thyroid cancer. Emphasis is given to data in children and aspects of linear growth and skeletal maturation.

  14. Diagnostic significance of /sup 99m/tc-marked phosphate uptake in the soft tissues of the breast

    Energy Technology Data Exchange (ETDEWEB)

    Bostel, F.; Meybier, H.

    1981-03-01

    A patient with a right-sided carcinoma of the breast had a bone scintigram with sup(99m)Tc-methylendisphosphonate (sup(99m)Tc-MDP), which showed intensive uptake in the abnormal breast; a year after mastectomy, similar high uptake of the drug was found in the remaining breast. The radiological findings indicated a fibrocystic mastopathy without evidence of malignancy in the left breast. A review of the literature suggested that uptake of osteotropic polyphosphate compounds in the breast was of considerable significance, indicating incipient or developing malignancy. A review of our own cases cast considerable doubt on this interpretation. It is probable that MDP uptake in the breast depends in part on the hormonal pattern and may occasionally be observed during oestrogen therapy in the male (e.g. carcinoma of the prostate).

  15. The diagnostic significance of sup(99m)TC-marked phosphate uptake in the soft tissues of the breast

    International Nuclear Information System (INIS)

    Bostel, F.; Meybier, H.; Heidelberg Univ.

    1981-01-01

    A patient with a right-sided carcinoma of the breast had a bone scintigram with sup(99m)Tc-methylendisphosphonate (sup(99m)Tc-MDP), which showed intensive uptake in the abnormal breast; a year after mastectomy, similar high uptake of the drug was found in the remaining breast. The radiological findings indicated a fibrocystic mastopathy without evidence of malignancy in the left breast. A review of the literature suggested that uptake of osteotropic polyphosphate compounds in the breast was of considerable significance, indicating incipient or developing malignancy. A review of our own cases cast considerable doubt on this interpretation. It is probable that MDP uptake in the breast depends in part on the hormonal pattern and may occasionally be observed during oestrogen therapy in the male (e.g. carcinoma of the prostate). (orig.) [de

  16. Response of the pigeon crop sac to mammotrophic hormones: Comparison between relaxin and prolactin

    International Nuclear Information System (INIS)

    Bani, G.; Sacchi, T.B.; Bigazzi, M.

    1990-01-01

    The effects of relaxin (RLX), a hormone that has previously been demonstrated to have mammotrophic properties, were studied in the pigeon crop sac, a well-known target organ for mammotrophic and lactogenic hormones, and compared with the effects produced by prolactin (PRL). The two hormones were injected directly over the crop at different doses and the response was evaluated after differing times of exposure. RLX causes a dose-related increase in wet and dry weights and [ 3 H]thymidine and [ 3 H]uridine uptake by the crop mucosa, as well as morphological changes indicating growth and differentiation of the epithelial cells similar to those occurring during physiological activation in incubation and hatching. At the doses assayed, the effects of RLX were nearly identical to those obtained following PRL in the short-term experiments, but differences in functional responses were found in the long-term experiment

  17. Amiodarone: Effects on thyroid function and the peripheral metabolism of the thyroid hormones

    International Nuclear Information System (INIS)

    Braverman, L.E.; Safran, M.; Bambini, G.; Pinchera, A.; Martino, E.

    1985-01-01

    In addition to the effects of Amiodarone on the peripheral metabolism of the thyroid hormones and on pituitary TSH secretion, a major complication of therapy is the relatively high frequency of iodide-induced thyroid dysfunction. The mean T 4 and T 3 concentration following Amiodarone application was measured in euthyroid, hypothyroid and hyperthyroid patients and in control patients with and without cardiac disorders. Furthermore, the serum TSH was determined in euthyroid Amiodarone-treated euthyroid patients. 131 I uptake was studied in patients with Amiodarone-associated thyrotoxicosis. The difficulties of the therapy of Amiodarone-induced hyper-thyroidism are outlined. Preliminary studied of the effect of Amiodarone and its analogues on the metabolism of thyroid hormones in the rat indicate that Amiodarone may act as a thyroid hormone agonist in the pituitary. (MG)

  18. Cell-Penetrating Ability of Peptide Hormones: Key Role of Glycosaminoglycans Clustering

    Directory of Open Access Journals (Sweden)

    Armelle Tchoumi Neree

    2015-11-01

    Full Text Available Over the last two decades, the potential usage of cell-penetrating peptides (CPPs for the intracellular delivery of various molecules has prompted the identification of novel peptidic identities. However, cytotoxic effects and unpredicted immunological responses have often limited the use of various CPP sequences in the clinic. To overcome these issues, the usage of endogenous peptides appears as an appropriate alternative approach. The hormone pituitary adenylate-cyclase-activating polypeptide (PACAP38 has been recently identified as a novel and very efficient CPP. This 38-residue polycationic peptide is a member of the secretin/glucagon/growth hormone-releasing hormone (GHRH superfamily, with which PACAP38 shares high structural and conformational homologies. In this study, we evaluated the cell-penetrating ability of cationic peptide hormones in the context of the expression of cell surface glycosaminoglycans (GAGs. Our results indicated that among all peptides evaluated, PACAP38 was unique for its potent efficiency of cellular uptake. Interestingly, the abilities of the peptides to reach the intracellular space did not correlate with their binding affinities to sulfated GAGs, but rather to their capacity to clustered heparin in vitro. This study demonstrates that the uptake efficiency of a given cationic CPP does not necessarily correlate with its affinity to sulfated GAGs and that its ability to cluster GAGs should be considered for the identification of novel peptidic sequences with potent cellular penetrating properties.

  19. Network identification of hormonal regulation

    NARCIS (Netherlands)

    Vis, D.J.; Westerhuis, J.A.; Hoefsloot, H.C.J.; Roelfsema, F.; Greef, J. van der; Hendriks, M.M.W.B.; Smilde, A.K.

    2014-01-01

    Relations among hormone serum concentrations are complex and depend on various factors, including gender, age, body mass index, diurnal rhythms and secretion stochastics. Therefore, endocrine deviations from healthy homeostasis are not easily detected or understood. A generic method is presented for

  20. Hormonal signaling in plant immunity

    NARCIS (Netherlands)

    Caarls, L.

    2016-01-01

    Insect hervivores and pathogens are a major problem in agriculture and therefore, control of these pests and diseases is essential. For this, understanding the plant immune response can be instrumental. The plant hormones salicylic acid (SA) and jasmonic acid (JA) play an essential role in defense

  1. Parathyroid Hormone Levels and Cognition

    Science.gov (United States)

    Burnett, J.; Smith, S.M.; Aung, K.; Dyer, C.

    2009-01-01

    Hyperparathyroidism is a well-recognized cause of impaired cognition due to hypercalcemia. However, recent studies have suggested that perhaps parathyroid hormone itself plays a role in cognition, especially executive dysfunction. The purpose of this study was to explore the relationship of parathyroid hormone levels in a study cohort of elders with impaied cognition. Methods: Sixty community-living adults, 65 years of age and older, reported to Adult Protective Services for self-neglect and 55 controls matched (on age, ethnicity, gender and socio-economic status) consented and participated in this study. The research team conducted in-home comprehensive geriatric assessments which included the Mini-mental state exam (MMSE), the 15-item geriatric depression scale (GDS) , the Wolf-Klein clock test and a comprehensive nutritional panel, which included parathyroid hormone and ionized calcium. Students t tests and linear regression analyses were performed to assess for bivariate associations. Results: Self-neglecters (M = 73.73, sd=48.4) had significantly higher PTH levels compared to controls (M =47.59, sd=28.7; t=3.59, df=98.94, pcognitive measures. Conclusion: Parathyroid hormone may be associated with cognitive performance.

  2. Incretin hormones--an update

    DEFF Research Database (Denmark)

    Holst, J J; Orskov, C

    2001-01-01

    important incretin hormones are glucose-dependent insulinotropic polypeptide (GIP, previously known as gastric inhibitory polypeptide) and glucagon-like peptide-1 (GLP-1) from the upper and lower small intestinal mucosa, respectively. It has been shown that interference with the incretin function causes...

  3. Transdermal Spray in Hormone Delivery

    African Journals Online (AJOL)

    market for the delivery system and ongoing development of transdermal sprays for hormone ... (DOAJ), African Journal Online, Bioline International, Open-J-Gate and Pharmacy Abstracts ... patches and gels have been very popular owing ... This product was developed for ... In a safety announcement, the US Food and.

  4. Quo vadis plant hormone analysis?

    Czech Academy of Sciences Publication Activity Database

    Tarkowská, Danuše; Novák, Ondřej; Floková, Kristýna; Tarkowski, P.; Turečková, Veronika; Grúz, Jiří; Rolčík, Jakub; Strnad, Miroslav

    2014-01-01

    Roč. 240, č. 1 (2014), s. 55-76 ISSN 0032-0935 R&D Projects: GA MŠk(CZ) LO1204 Institutional support: RVO:61389030 Keywords : Plant hormones * Extraction * Mass spectrometr Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.263, year: 2014

  5. Parathyroid hormone and bone healing

    DEFF Research Database (Denmark)

    Ellegaard, M; Jørgensen, N R; Schwarz, P

    2010-01-01

    , no pharmacological treatments are available. There is therefore an unmet need for medications that can stimulate bone healing. Parathyroid hormone (PTH) is the first bone anabolic drug approved for the treatment of osteoporosis, and intriguingly a number of animal studies suggest that PTH could be beneficial...

  6. Hormones and growth factors in breast cancer

    African Journals Online (AJOL)

    Herman-Giddens M. Condylomata acuminata in children and sexual abuse. Genitourin ..... accommodated reasonably easily in the outline of hormone action referred to ... tumours may still respond to hormone manipulation with another type of ...

  7. Follicle-stimulating hormone (FSH) blood test

    Science.gov (United States)

    ... ency/article/003710.htm Follicle-stimulating hormone (FSH) blood test To use the sharing features on this page, please enable JavaScript. The follicle stimulating hormone (FSH) blood test measures the level of FSH in blood. FSH ...

  8. Pituitary-hormone secretion by thyrotropinomas

    NARCIS (Netherlands)

    Roelfsema, Ferdinand; Kok, Simon; Kok, Petra; Pereira, Alberto M.; Biermasz, Nienke R.; Smit, Jan W.; Frolich, Marijke; Keenan, Daniel M.; Veldhuis, Johannes D.; Romijn, Johannes A.

    2009-01-01

    Hormone secretion by somatotropinomas, corticotropinomas and prolactinomas exhibits increased pulse frequency, basal and pulsatile secretion, accompanied by greater disorderliness. Increased concentrations of growth hormone (GH) or prolactin (PRL) are observed in about 30% of thyrotropinomas leading

  9. Growth hormone stimulation test - series (image)

    Science.gov (United States)

    The growth hormone (GH) is a protein hormone released from the anterior pituitary gland under the control of the hypothalamus. In children, GH has growth-promoting effects on the body. It stimulates the ...

  10. In vivo effect of sex steroids on uptake of 3H-leucine by female mouse brain

    International Nuclear Information System (INIS)

    Seiki, Kanji; Haruki, Yasuo; Imanishi, Yoshio

    1978-01-01

    In vivo effects of the sex steroids estrogen and progesterone on 3 H-leucine uptake by the brain of mature ovariectomized mice were examined. Animals were divided into three groups: group 1, consisting of control animals treated with sesame oil, group 2, animals treated with estrogen, and group 3, animals first treated with estrogen and then with progesterone. Each group was given a single i.p. injection of 3 H-leucine 2 hr after the last hormonal treatment, and sacrificed 2 hr later. Intensity of the uptake of radiolabeled leucine was measured by counting the number of reduced silver grains over cells in various brain regions using an autoradiographic technique. Group 1 showed a relatively high uptake in the supraoptic nucleus, paraventricular nucleus (PV) and ventromedial nucleus (VM) when compared with that in the remaining hypothalamic nuclei examined. Group 2 showed a significant enhancement of the uptake in all hypothalamic regions except the preoptic periventricular nucleus (PPV) when compared with that in group 1. Group 3 showed enhancement of the uptake in all hypothalamic nuclei when compared with that in group 1. However, only the PV, PPV, VM and periventricular arcuate nucleus revealed a significantly higher uptake than the respective nuclei in group 2. The remaining nuclei showed no change in uptake. Uptake by cells in the ependymal cells and cerebral cortex remained unchanged after hormonal treatment. The present results suggest that in female mice estrogen and estrogen plus progesterone stimulate protein synthesis in most of the hypothalamic nuclei and that the progesterone effect on protein synthesis is greatly influenced by estrogen-priming. (auth.)

  11. DNA Uptake by Transformable Bacteria

    Energy Technology Data Exchange (ETDEWEB)

    Lacks, Sanford A.

    1999-03-31

    The various processes of DNA uptake by cells can be categorized as: viral DNA entry, conjugation, or transformation. Within each category, a variety of mechanisms have been found. However, considerable similarities occur among the different mechanisms of conjugation and, especially, transformation. All of these natural mechanisms of DNA transfer are quite elaborate and involve multiple protein components, as the case may be, of the virus, the donor cell, and the recipient cell. The mechanisms of viral infection and conjugation will be discussed mainly with respect to their relevance to transformation.

  12. DNA UPTAKE BY TRANSFORMABLE BACTERIA

    Energy Technology Data Exchange (ETDEWEB)

    LACKS,S.A.

    1999-09-07

    The various processes of DNA uptake by cells can be categorized as: viral DNA entry, conjugation, or transformation. Within each category, a variety of mechanisms have been found. However, considerable similarities occur among the different mechanisms of conjugation and, especially, transformation. All of these natural mechanisms of DNA transfer are quite elaborate and involve multiple protein components, as the case may be, of the virus, the donor cell, and the recipient cell. The mechanisms of viral infection and conjugation will be discussed mainly with respect to their relevance to transformation.

  13. The effects of thyroid hormones on brown adipose tissue in humans: a PET-CT study.

    Science.gov (United States)

    Zhang, Qiongyue; Miao, Qing; Ye, Hongying; Zhang, Zhaoyun; Zuo, Chuantao; Hua, Fengchun; Guan, Yihui; Li, Yiming

    2014-09-01

    Brown adipose tissue (BAT) is important for energy expenditure through thermogenesis, although its regulatory factors are not well known in humans. There is evidence suggesting that thyroid hormones affect BAT functions in some mammals, but the effects of thyroid hormones on BAT activity in humans are still unclear. The aim of this study was to investigate the effects of thyroid hormones on glucose metabolism of BAT and other organs in humans. Nine Graves' disease-caused hyperthyroid patients who were newly diagnosed and untreated were studied. Putative brown adipose tissue activity was determined by the integrated ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron-emission tomography and computed tomography (PET-CT). All hyperthyroid patients were treated with methimazole and had been monitored until their symptoms disappeared and thyroid hormone levels returned to normal. At the end, a second PET-CT scan was performed. The average follow-up period was 77 days. Meanwhile, compared with a group of seventy-five brown adipose tissue-negative controls, thyroid hormones of seventy-five BAT-positive healthy subjects were measured. Active brown adipose tissue was not present in any of the hyperthyroid patients. However, one patient with normalized thyroid function showed active BAT after therapy. The free T3 levels and free T4 levels were significantly lower in the 75 BAT-positive subjects than in the BAT-negative subjects. All hyperthyroid patients showed symmetrically increased uptake of fluorodeoxyglucose in skeletal muscles before treatment, whereas, the standardized uptake value was substantially decreased after treatment. Abnormally high circulating thyroid hormone levels may not increase brown adipose tissue activity, which may be limited by the increased obligatory thermogenesis of muscle in adult humans. Copyright © 2014 John Wiley & Sons, Ltd.

  14. Headaches and Hormones: What's the Connection?

    Science.gov (United States)

    Headaches and hormones: What's the connection? Being female has some real health advantages, but not when it comes to headaches — particularly ... a relationship between headaches and hormonal changes. The hormones estrogen (ES-truh-jen) and progesterone (pro-JES- ...

  15. Peptide Hormones in the Gastrointestinal Tract

    DEFF Research Database (Denmark)

    Rehfeld, Jens F.

    2015-01-01

    Gastrointestinal hormones are peptides released from endocrine cells and neurons in the digestive tract. More than 30 hormone genes are currently known to be expressed in the gastrointestinal tract, which makes the gut the largest hormone-producing organ in the body. Modern biology makes it feasi...

  16. Parathyroid hormone-related protein blood test

    Science.gov (United States)

    ... ency/article/003691.htm Parathyroid hormone-related protein blood test To use the sharing features on this page, ... measures the level of a hormone in the blood, called parathyroid hormone-related protein. How the Test is Performed A blood sample is needed . How ...

  17. Thyroid hormone signaling in the hypothalamus

    NARCIS (Netherlands)

    Alkemade, Anneke; Visser, Theo J.; Fliers, Eric

    2008-01-01

    PURPOSE OF REVIEW: Proper thyroid hormone signaling is essential for brain development and adult brain function. Signaling can be disrupted at many levels due to altered thyroid hormone secretion, conversion or thyroid hormone receptor binding. RECENT FINDINGS: Mutated genes involved in thyroid

  18. Obesity, growth hormone and weight loss

    DEFF Research Database (Denmark)

    Rasmussen, Michael Højby

    2009-01-01

    Growth hormone (GH) is the most important hormonal regulator of postnatal longitudinal growth in man. In adults GH is no longer needed for longitudinal growth. Adults with growth hormone deficiency (GHD) are characterised by perturbations in body composition, lipid metabolism, cardiovascular risk...

  19. Correlations Between Seminal Plasma Hormones and Sperm ...

    African Journals Online (AJOL)

    Context: There is a complex relationship between seminal plasma hormone levels and infertility in men. Previous studies had shown no specific pattern in the serum or seminal plasma hormone profiles of men with infertility and it is debatable whether there is a need to perform routine seminal hormone assays in the ...

  20. Thyrotoxicosis caused by functioning metastatic thyroid carcinoma. A rare and elusive cause of hyperthyroidism with low radioactive iodine uptake

    International Nuclear Information System (INIS)

    Ober, K.P.; Cowan, R.J.; Sevier, R.E.; Poole, G.J.

    1987-01-01

    A patient with progressively worsening thyrotoxicosis, refractory to medical therapy, is described. Repeated measurements of thyroidal RAI uptake over a 13 month period were low consistently and could not be explained by iodine ingestion, thyroiditis, or administration of exogenous thyroid hormone. An I-131 scan ultimately revealed striking activity at the base of the skull, reflecting ectopic excessive production of thyroid hormone by a solitary functioning metastatic thyroid carcinoma. The thyrotoxic state resolved after large doses of therapeutic I-131. Typical features of this rare cause of hyperthyroidism are discussed

  1. Ocean uptake of carbon dioxide

    International Nuclear Information System (INIS)

    Peng, Tsung-Hung; Takahashi, Taro

    1993-01-01

    Factors controlling the capacity of the ocean for taking up anthropogenic C0 2 include carbon chemistry, distribution of alkalinity, pCO 2 and total concentration of dissolved C0 2 , sea-air pCO 2 difference, gas exchange rate across the sea-air interface, biological carbon pump, ocean water circulation and mixing, and dissolution of carbonate in deep sea sediments. A general review of these processes is given and models of ocean-atmosphere system based on our understanding of these regulating processes axe used to estimate the magnitude of C0 2 uptake by the ocean. We conclude that the ocean can absorb up to 35% of the fossil fuel emission. Direct measurements show that 55% Of C0 2 from fossil fuel burning remains in the atmosphere. The remaining 10% is not accounted for by atmospheric increases and ocean uptake. In addition, it is estimated that an amount equivalent to 30% of recent annual fossil fuel emissions is released into the atmosphere as a result of deforestation and farming. To balance global carbon budget, a sizable carbon sink besides the ocean is needed. Storage of carbon in terrestrial biosphere as a result of C0 2 fertilization is a potential candidate for such missing carbon sinks

  2. Highly potent metallopeptide analogues of luteinizing hormone-releasing hormone

    International Nuclear Information System (INIS)

    Bajusz, S.; Janaky, T.; Csernus, V.J.; Bokser, L.; Fekete, M.; Srkalovic, G.; Redding, T.W.; Schally, A.V.

    1989-01-01

    Metal complexes related to the cytotoxic complexes cisplatin [cis-diamminedichloroplatinum(II)] and transbis(salicylaldoximato)copper(II) were incorporated into suitably modified luteinizing hormone-releasing hormone (LH-RH) analogues containing D-lysine at position 6. Some of the metallopeptides thus obtained proved to be highly active LH-RH agonists or antagonists. Most metallopeptide analogues of LH-RH showed high affinities for the membrane receptors of rat pituitary and human breast cancer cells. Some of these metallopeptides had cytotoxic activity against human breast cancer and prostate cancer and prostate cancer cell lines in vitro. Such cytostatic metallopeptides could be envisioned as targeted chemotherapeutic agents in cancers that contain receptors for LH-RH-like peptides

  3. Thyroid hormone uptake in cultured rat anterior pituitary cells: effects of energy status and bilirubin

    NARCIS (Netherlands)

    F.W.J.S. Wassen (Frank); E.P.C.M. Moerings (Ellis); H. van Toor (Hans); G. Hennemann; M.E. Everts (Maria)

    2000-01-01

    textabstractTransport of thyroxine (T(4)) into the liver is inhibited in fasting and by bilirubin, a compound often accumulating in the serum of critically ill patients. We tested the effects of chronic and acute energy deprivation, bilirubin and its precursor

  4. effect of plant hormones on the growth and nutrient uptake of maize

    African Journals Online (AJOL)

    Preferred Customer

    prolonged vegetative growth, which resulted in decreased grain yield. The investigation of Caldiz et al. (1991) also indicated that foliar application of. BA and nitrogen on wheat plants delayed chlorophyll loss in the flag leaf but modified neither yield nor yield components. Benzylad- ennine (BA) increased only grain protein.

  5. Glucagon effects on the membrane potential and calcium uptake rate of rat liver mitochondria

    International Nuclear Information System (INIS)

    Wingrove, D.E.; Amatruda, J.M.; Gunter, T.E.

    1984-01-01

    It has been widely reported that the in vivo administration of glucagon to rats results in the stimulation of calcium influx in subsequently isolated liver mitochondria. The mechanism of this effect is investigated through simultaneous measurements of calcium uptake rate and mitochondrial membrane potential. This allows the measurement of the calcium uniporter conductance independent of hormonal effects on electron transport or respiration. Two experimental approaches are used. The first involves measuring the uptake of 40-50 nmol of Ca 2+ /mg of mitochondrial protein with the calcium dye antipyrylazo III; the second uses 45 Ca 2+ to follow uptake in the presence of 0.5 to 1.5 μM free calcium, buffered with HEDTA. In both cases a tetraphenyl phosphonium electrode is used to follow membrane potential, and membrane potential is varied using either malonate or butylmalonate in the presence of rotenone. The relative merits of these two approaches are discussed. The conductance of the calcium uniporter is found not to be stimulated by glucagon pretreatment. Also, the relative glucagon stimulation of both calcium influx and membrane potential is found to increase with increasing malonate concentration. These results imply that there is no direct stimulation of calcium uptake into liver mitochondria following glucagon treatment. The results are consistent with a glucagon stimulation of substrate transport, substrate oxidation, or a stimulation of electron transport resulting in an increased membrane potential and secondary stimulation of calcium uptake

  6. Modulation of liver mitochondrial NOS is implicated in thyroid-dependent regulation of O(2) uptake.

    Science.gov (United States)

    Carreras, M C; Peralta, J G; Converso, D P; Finocchietto, P V; Rebagliati, I; Zaninovich, A A; Poderoso, J J

    2001-12-01

    Changes in O(2) uptake at different thyroid status have been explained on the basis of the modulation of mitochondrial enzymes and membrane biophysical properties. Regarding the nitric oxide (NO) effects, we tested whether liver mitochondrial nitric oxide synthase (mtNOS) participates in the modulation of O(2) uptake in thyroid disorders. Wistar rats were inoculated with 400 microCi (131)I (hypothyroid group), 20 microg thyroxine (T(4))/100 g body wt administered daily for 2 wk (hyperthyroid group) or vehicle (control). Basal metabolic rate, mitochondrial function, and mtNOS activity were analyzed. Systemic and liver mitochondrial O(2) uptake and cytochrome oxidase activity were lower in hypothyroid rats with respect to controls; mitochondrial parameters were further decreased by L-arginine (-42 and -34%, P activity (260%) were selectively increased in hypothyroidism and reverted by hormone replacement without changes in other nitric oxide isoforms. Moreover, mtNOS activity correlated with serum 3,5,3'-triiodothyronine (T(3)) and O(2) uptake. Increased mtNOS activity was also observed in skeletal muscle mitochondria from hypothyroid rats. Therefore, we suggest that modulation of mtNOS is a substantial part of thyroid effects on mitochondrial O(2) uptake.

  7. Studies on the T sub 3 suppression test with reference to the thyrodial sup 123 I uptake in Graves' disease; Comparison of 24-hour and 3-hour uptake

    Energy Technology Data Exchange (ETDEWEB)

    Yamaguchi, Takahiko; Kobayashi, Isao; Yamaguchi, Yoshiyuki; Iwashita, Akira; Inukai, Toshihiko; Ohshima, Kihachi; Shimomura, Yohnosuke; Kobayashi, Setsuo (Gunma Univ., Maebashi (Japan). School of Medicine)

    1990-06-01

    Eighty-three patients with Graves' disease had been treated with methylmercaptoimidazole (MMI). They were prescribed a maintenance dose of antithyroid drug (MMI, 5 mg/day) at the time of a T{sub 3} suppression test. The 3-hour and 24-hour thyroidal {sup 123}I uptake after T{sub 3} administration (75 {mu}g/day, 2 weeks) were measured (post T{sub 3} uptake). In 38 patients whose post T{sub 3} uptake was below 35% in post T{sub 3} 24-hour uptake, treatment was stopped. The T{sub 3} suppression test was then repeated 1 and 3 months later. During a one-year follow up, 26 remained well, while 12 relapsed within 6 to 12 months. We have observed a good correlation between 3-hour uptake and 24-hour uptake of {sup 123}I after T{sub 3} administration (r=0.847, p<0.001). In 38 patients who showed positive T{sub 3} suppression, most patients with MMI withdrawal produced a marked overshoot of post T{sub 3} 3-hour and 24-hour uptake at one month. Retrospective analysis indicated that there was no significant difference in circulating thyroid hormone levels between remission and relapse groups. The present study provides evidence that 3-hour uptake values are able to be substituted for 24-hour uptake values during a T{sub 3} suppression test. In addition, overshoot of thyroidal uptake after antithyroid drug withdrawal was observed in 3-hour values, similar to 24-hour values. (author).

  8. The interrelationships of thyroid and growth hormones: effect of growth hormone releasing hormone in hypo- and hyperthyroid male rats.

    Science.gov (United States)

    Root, A W; Shulman, D; Root, J; Diamond, F

    1986-01-01

    Growth hormone (GH) and the thyroid hormones interact in the hypothalamus, pituitary and peripheral tissues. Thyroid hormone exerts a permissive effect upon the anabolic and metabolic effects of GH, and increases pituitary synthesis of this protein hormone. GH depresses the secretion of thyrotropin and the thyroid hormones and increases the peripheral conversion of thyroxine to triiodothyronine. In the adult male rat experimental hypothyroidism produced by ingestion of propylthiouracil depresses the GH secretory response to GH-releasing hormone in vivo and in vitro, reflecting the lowered pituitary stores of GH in the hypothyroid state. Short term administration of large amounts of thyroxine with induction of the hyperthyroid state does not affect the in vivo GH secretory response to GH-releasing hormone in this animal.

  9. The physiology of growth hormone and sport.

    LENUS (Irish Health Repository)

    Widdowson, W Matthew

    2012-02-01

    The growth hormone (GH)\\/ insulin-like growth factor-I (IGF-I) axis exerts short-and long-term metabolic effects that are potentially important during exercise. Exercise is a potent stimulus to GH release and there is some evidence that the acute increase in GH is important in regulating substrate metabolism post-exercise. Regular exercise also increases 24-hour GH secretion rates, which potentially contributes to the physiologic changes induced by training. The effects of GH replacement in GH-deficient adults provide a useful model with which to study the effects of the more long-term effects of the GH\\/ IGF-I axis. There is convincing evidence that GH replacement increases exercise capacity. Measures of exercise performance including maximal oxygen uptake (VO2max) and ventilatory threshold (VeT) are impaired in GH deficiency and improved by GH replacement, probably through some combination of increased oxygen delivery to exercising muscle, increased fatty acid availability with glycogen sparing, increased muscle strength, improved body composition and improved thermoregulation. Administration of supraphysiologic doses of GH to athletes increases fatty acid availability and reduces oxidative protein loss particularly during exercise, and increases lean body mass. It is not known whether these effects translate to improved athletic performance, although recombinant human GH is known to be widely abused in sport. The model of acromegaly provides evidence that long-term GH excess does not result in improved performance but it is possible that a "window" exists in which the protein anabolic effects of supraphysiologic GH might be advantageous.

  10. Reproductive Hormones and Mood Disorders

    Directory of Open Access Journals (Sweden)

    Sermin Kesebir

    2010-12-01

    Full Text Available During the menstrual cycle, pregnancy and breast-feeding periods, as well as in menopausal and post-menopausal periods, the physiological and psychological processes that change according to the hormonal fluctuations influence every women similarly and each one differently. These physiological processes are controlled by neuroendocrine sequences, of which the hypothalamo-pituitary-adrenal axis and the hypothalamo-pituitary-gonadal axis are the most important ones. The hypothalamo-pituitary-gonadal axis affects mood, anxiety, cognition and pain. The interaction of these hormones with mood and behavior is bidirectional. The differences in phenomenology and epidemiology of mood disorders with regards to gender can be explained with the effects of hormones. All of the periods mentioned above are related with mood disorders at terms of risk factors, disease symptoms, progress of disease and response to treatment. Epidemiologic data supports the relationship between the mood disorders and reproductive processes. The prevalence of major depression increases in women with the menarche and ceases in post- menopausal period. Similarly, the initial symptoms of bipolar disorder begins around the menarche period in 50% of the cases. Despite proper treatment, some female patients with major depression experience recurrence during the premenstrual period of their menstrual cycles. The conformity and change in a woman’s brain during pregnancy is controlled dominantly by the neuroendocrine systems, while it is controlled by the external stimuli actively related to the baby during nursing period. The changes that occur are closely related to postpartum mood disorders. Again, all the changes and suspension of medication during this procedure are risk factors for early depressive and dysphoric situations. Variables of a wide range, from follicle stimulating hormone, melatonin, and sleep to body mass index interact with mood disorders in menopausal and post

  11. Changes of FDG brain uptake in patients with abnormal thyroid function

    International Nuclear Information System (INIS)

    Huang, Wen-Sheng; Chang, Chih-Yung; Cheng, Cheng Yi

    2009-01-01

    Full text: Objective: To investigate FOG brain uptake in patients with hypo- and subclinical hyperthyroidism undergoing whole-body FOG PET/CT. Methods: Sixty-four patients who had received total thyroidectomy for thyroid carcinoma underwent whole-body FDG PETI CT. Thirty-two of them received imaging in subclinical hyperthyroid status (15 males; 17 females; mean age, 55 ± 14 years) while the other 32 age-matched patients underwent the scan 4 wk after thyroid hormone withdrawal (12 males; 20 females; mean age, 56 ± 13 years). Brain images were performed I h after 370 MBq intravenous injection using a dedicated PET/CT (Siemens Biograph BGO duo). FOG-uptake was quantified by the standardized uptake value (SUY), normalized to patient's body weight. The volume of brain was determined by PET with 40% maximum SUY threshold. The brain mean SUV (SUY mean) were calculated in each patient. Data were compared between the two groups. Results: The brain mean SUYs for the hypothyroid patients ranged between 3.11 and 6.35 (averaged SUY mean 5.13 ± 0.91) while those of the subclinical hyperthyroid patients varied from 3.53 to 8.29 (mean SUY mean 5.77 ± 1.04). There was a significant global reduction of brain FDG uptake in the hypothyroid group (II.] %, P < 0.0 I) but no significant changes in the sub-clinical hyperthyroid group compared to the controls. Conclusion: FDG brain uptake in subclinical hyperthyroid patients was significantly greater than that of patients with hypothyroidism, suggesting effects of thyroid hormone on cerebral glucose metabolism.

  12. {sup 99m}Tc-sestamibi thyroid uptake in euthyroid individuals and in patients with autoimmune thyroid disease

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Allan O. [Campinas State University, Division of Nuclear Medicine, Department of Radiology, School of Medical Sciences, Campinas (Brazil); Avenida Independencia, Piracicaba, Sao Paulo (Brazil); Zantut-Wittmann, D.E.; Tambascia, M.A. [Campinas State University, Division of Endocrinology, Department of Internal Medicine, School of Medical Sciences, Campinas (Brazil); Nogueira, R.O.; Etchebehere, E.C.S.C.; Lima, M.C.L.; Camargo, E.E.; Ramos, C.D. [Campinas State University, Division of Nuclear Medicine, Department of Radiology, School of Medical Sciences, Campinas (Brazil)

    2005-06-01

    We investigated the biokinetics of {sup 99m}Tc-sestamibi in the thyroid of euthyroid volunteers (EVs) and in patients with autoimmune thyroid diseases and determined the best time interval between {sup 99m}Tc-sestamibi injection and calculation of uptake. Forty EVs, 30 patients with Graves' disease (GD), 15 patients with atrophic Hashimoto's thyroiditis (AHT) and 15 patients with hypertrophic Hashimoto's thyroiditis (HHT) underwent {sup 99m}Tc-sestamibi thyroid scintigraphy. Dynamic images were acquired for 20 min, and static images were obtained 20 min, 60 min and 120 min post injection. Five-, 20-, 60- and 120-min uptake, time to maximal uptake (T{sub max}) and T{sub 1/2} of tracer clearance were calculated. Thyroid hormones and antibodies were measured. {sup 99m}Tc-pertechnetate uptake was investigated in GD patients. T{sub max} was approximately 5 min in all four groups. The mean T{sub 1/2} value for EVs was similar to the GD value and lower than the HHT and AHT values. The mean ({+-}SD) 5-min uptake was 0.13% ({+-}0.05%) for EVs. The 5-min uptake in GD was higher than that in EVs(P<0.001) and correlated with free thyroxine (r=0.54) and with {sup 99m}Tc-pertechnetate uptake (r=0.68). Uptake in HHT was higher than that in AHT (P=0.0003) and EVs (P=0.002). Uptake in AHT was lower than uptake in EVs (P=0.0001). Five minutes is the optimal time interval between {sup 99m}Tc-sestamibi injection and calculation of thyroid uptake. Five-minute uptake differentiates euthyroid individuals from GD patients. There is a high correlation between {sup 99m}Tc-sestamibi and {sup 99m}Tc-pertechnetate uptake in GD. The reduced {sup 99m}Tc-sestamibi uptake in AHT patients is probably due to glandular destruction and fibrosis. Inflammatory infiltrate and high mitochondrial density in thyrocytes possibly explain the increased uptake in GD and HHT. (orig.)

  13. Increased muscle glucose uptake during contractions

    DEFF Research Database (Denmark)

    Ploug, Thorkil; Galbo, Henrik; Richter, Erik

    1984-01-01

    We reinvestigated the prevailing concept that muscle contractions only elicit increased muscle glucose uptake in the presence of a so-called "permissive" concentration of insulin (Berger et al., Biochem. J. 146: 231-238, 1975; Vranic and Berger, Diabetes 28: 147-163, 1979). Hindquarters from rats...... in severe ketoacidosis were perfused with a perfusate containing insulin antiserum. After 60 min perfusion, electrical stimulation increased glucose uptake of the contracting muscles fivefold. Also, subsequent contractions increased glucose uptake in hindquarters from nondiabetic rats perfused for 1.5 h......-methylglucose uptake increased during contractions and glucose uptake was negative at rest and zero during contractions. An increase in muscle transport and uptake of glucose during contractions does not require the presence of insulin. Furthermore, glucose transport in contracting muscle may only increase if glycogen...

  14. Cell uptake survey of pegylated nanographene oxide.

    Science.gov (United States)

    Vila, M; Portolés, M T; Marques, P A A P; Feito, M J; Matesanz, M C; Ramírez-Santillán, C; Gonçalves, G; Cruz, S M A; Nieto, A; Vallet-Regi, M

    2012-11-23

    Graphene and more specifically, nanographene oxide (GO) has been proposed as a highly efficient antitumoral therapy agent. Nevertheless, its cell uptake kinetics, its influence in different types of cells and the possibility of controlling cellular internalization timing, is still a field that remains unexplored. Herein, different cell types have been cultured in vitro for several incubation periods in the presence of 0.075 mg ml(-1) pegylated GO solutions. GO uptake kinetics revealed differences in the agent's uptake amount and speed as a function of the type of cell involved. Osteoblast-like cells GO uptake is higher and faster without resulting in greater cell membrane damage. Moreover, the dependence on the commonly used PEG nature (number of branches) also influences the viability and cell uptake speed. These facts play an important role in the future definition of timing parameters and selective cell uptake control in order to achieve an effective therapy.

  15. Cell uptake survey of pegylated nanographene oxide

    International Nuclear Information System (INIS)

    Vila, M; Nieto, A; Vallet-Regi, M; Portolés, M T; Feito, M J; Matesanz, M C; Ramírez-Santillán, C; Marques, P A A P; Gonçalves, G; Cruz, S M A

    2012-01-01

    Graphene and more specifically, nanographene oxide (GO) has been proposed as a highly efficient antitumoral therapy agent. Nevertheless, its cell uptake kinetics, its influence in different types of cells and the possibility of controlling cellular internalization timing, is still a field that remains unexplored. Herein, different cell types have been cultured in vitro for several incubation periods in the presence of 0.075 mg ml −1 pegylated GO solutions. GO uptake kinetics revealed differences in the agent’s uptake amount and speed as a function of the type of cell involved. Osteoblast-like cells GO uptake is higher and faster without resulting in greater cell membrane damage. Moreover, the dependence on the commonly used PEG nature (number of branches) also influences the viability and cell uptake speed. These facts play an important role in the future definition of timing parameters and selective cell uptake control in order to achieve an effective therapy. (paper)

  16. Gastric gallium-67 uptake in gastritis

    International Nuclear Information System (INIS)

    Yeh, E.L.; Tisdale, P.L.; Zielonka, J.S.

    1983-01-01

    Even though Ga-67 imaging has been used widely in the diagnosis of malignant as well as inflammatory lesions, its uptake in the stomach has been reported in the literature mainly in gastric lymphoma and carcinoma. As shown in this case, intense gastric uptake of the radionuclide may be seen in common gastritis without malignancy. Perhaps the benign gastric uptake of Ga-67 deserves more emphasis

  17. Obesity and hormonal contraceptive efficacy.

    Science.gov (United States)

    Robinson, Jennifer A; Burke, Anne E

    2013-09-01

    Obesity is a major public health concern affecting an increasing proportion of reproductive-aged women. Avoiding unintended pregnancy is of major importance, given the increased risks associated with pregnancy, but obesity may affect the efficacy of hormonal contraceptives by altering how these drugs are absorbed, distributed, metabolized or eliminated. Limited data suggest that long-acting, reversible contraceptives maintain excellent efficacy in obese women. Some studies demonstrating altered pharmacokinetic parameters and increased failure rates with combined oral contraceptives, the contraceptive patch and emergency contraceptive pills suggest decreased efficacy of these methods. It is unclear whether bariatric surgery affects hormonal contraceptive efficacy. Obese women should be offered the full range of contraceptive options, with counseling that balances the risks and benefits of each method, including the risk of unintended pregnancy.

  18. Progress of measurement of hormones

    International Nuclear Information System (INIS)

    Ohsawa, Nakaaki

    1977-01-01

    Description was made as to an outline of the theory of radioreceptor assay (RRA) in which hormone receptor was used as specific binding protein, as same as the theory of RIA, and as to its practical use. Meaning of RRA for measurement of hormones in consideration of the site of immunological and biological activation and meaning of difference in measurement values between this method and in RIA in the same materials, were mentioned, and effectiveness of use of this method together with RIA was described. Detection of receptor site, analysis of binding specificity, and numerical calculation were mentioned as receptor analysis by this method. As practical use of these functions, arrangement mechanism of receptor, and analysis of abnormality were mentioned. Especially, analysis of testicular feminization syndrome, insulinresistenter diabetes, hyperthyroidism, and myasthenia gravis, and relationship between these diseases and autoimmune diseases were described, and clinical meaning of this method in internal medicine and surgery was mentioned. (Kanao, N.)

  19. Patient communication in hormone therapy.

    Science.gov (United States)

    Schnare, S M

    2001-01-01

    Common regimens of HRT therapy are reviewed, including common routes of hormone administration. Inconsistent patterns of HRT use are discussed, including the reasons women most often give for discontinuing hormone therapies. Specific issues related to misperceptions and fears regarding HRT are clarified, and specific, focused patient education formats are discussed to address women's common concerns about HRT. Obstacles to HRT use are elucidated, with suggestions for clinicians about how to communicate more effectively with women: clinicians must focus on emotional and physical aspects of HRT choices and tailor therapies to the individual patient. Discussing frankly the very serious concerns of women regarding the association between lobular breast cancer and endometrial cancer is important; discussing and preparing women for possible side effects helps patients cope better if and when side effects occur. Finally, offering a wide variety of HRT therapies provides women with a broader choice if an initial regimen is unsuccessful.

  20. Radioactive labelling of peptidic hormones

    International Nuclear Information System (INIS)

    Fromageot, P.; Pradelles, P.; Morgat, J.L.; Levine, H.

    1976-01-01

    The labelling of peptidic hormones requires stability, specificity and sensitivity of the label. Introduction of a radioactive atome is one way to satisfy these criteria. Several processes have been described to prepare radioactive TRF: synthesis of the peptide with labelled aminoacids or introduction of the label into the hormone. In that approach, tritium can be substituted in the imidazole ring, via precursors activating the proper carbon. Monoiodo TRF leads essentially to tritium labelling of the 5 positions whereas monoazo TRF allows the preparation of 3 H TRF labelled in the 2 positions. Di-substituted TRF leads to labelling into the 2 and 5 carbons. Labelled analogs of TRF can be prepared with labelled iodine; further developments of peptide labelling, will be presented. In particular, the homolytic scission of the C-iodine, bond by photochemical activation. The nascent carbon radical can be stabilized by a tritiated scavenger. This approach eliminates the use of heavy metal catalysts

  1. Would male hormonal contraceptives affect cardiovascular risk?

    Directory of Open Access Journals (Sweden)

    Michael Zitzmann

    2018-01-01

    Full Text Available The aim of hormonal male contraception is to prevent unintended pregnancies by suppressing spermatogenesis. Hormonal male contraception is based on the principle that exogenous administration of androgens and other hormones such as progestins suppress circulating gonadotropin concentrations, decreasing testicular Leydig cell and Sertoli cell activity and spermatogenesis. In order to achieve more complete suppression of circulating gonadotropins and spermatogenesis, a progestin has been added testosterone to the most recent efficacy trials of hormonal male contraceptives. This review focusses on the potential effects of male hormonal contraceptives on cardiovascular risk factors, lipids and body composition, mainly in the target group of younger to middle-aged men. Present data suggest that hormonal male contraception can be reasonably regarded as safe in terms of cardiovascular risk. However, as all trials have been relatively short (< 3 years, a final statement regarding the cardiovascular safety of hormonal male contraception, especially in long-term use, cannot be made. Older men with at high risk of cardiovascular event might not be good candidates for hormonal male contraception. The potential adverse effects of hormonal contraceptives on cardiovascular risk appear to depend greatly on the choice of the progestin in regimens for hormonal male contraceptives. In the development of prospective hormonal male contraception, data on longer-term cardiovascular safety will be essential.

  2. In vivo characterization of insulin uptake by dog renal cortical epithelium

    International Nuclear Information System (INIS)

    Whiteside, C.I.; Lumsden, C.J.; Silverman, M.

    1988-01-01

    In vivo 125I-labeled insulin uptake by dog renal tubular epithelium was studied using the single-pass multiple indicator dilution (MID) method and analyzed by a computer-assisted model of transcapillary exchange and substrate-cell interaction. Anesthetized dogs received an intrarenal arterial bolus of multiple tracers: [3H]dextran greater than 70 kDa (plasma reference), [14C]inulin (extracellular reference), and 125I-insulin. Rapid serial sampling of the renal venous and urine outflows was performed. The renal venous outflow curves of 125I-insulin fell below [14C]inulin implying postglomerular extraction and antiluminal membrane (ALM) uptake. The fractional urine recovery of 125I-insulin was less than 0.03, indicating luminal tubular uptake of filtered hormone. After intravenous infusion of unlabeled insulin, repeat MID runs with tracer revealed saturable ALM uptake as evidenced by the 125I-insulin renal venous outflow curves approaching [14C]inulin. Luminal tubular uptake was unchanged and therefore unsaturable. The 125I-insulin renal venous data were studied using three mathematical models, incorporating postglomerular reversible binding, irreversible binding or transport. The best fit was obtained using the transport model. The modeling analysis is consistent with either uptake into a virtual epithelial membrane space (i.e., insulin never enters the cell but binds to or is distributed along the ALM) or insulin actually enters the intracellular compartment. In vivo uptake of 125I-insulin ALM is characterized by a Km of 15.44 nM

  3. BIOTECHNOLOGY OF RECOMBINANT HORMONES IN DOPING

    Directory of Open Access Journals (Sweden)

    Biljana Vitošević

    2011-09-01

    Full Text Available Recombinant DNA technology has allowed rapid progress in creating biosynthetic gene products for the treatment of many diseases. In this way it can produce large amounts of hormone, which is intended for the treatment of many pathological conditions. Recombinant hormones that are commonly used are insulin, growth hormone and erythropoietin. Precisely because of the availability of these recombinant hormones, it started their abuse by athletes. Experiments in animal models confirmed the potential effects of some of these hormones in increasing physical abilities, which attracted the attention of athletes who push the limits of their competitive capability by such manipulation. The risks of the use of recombinant hormones in doping include serious consequences for the health of athletes. Methods of detection of endogenous hormones from recombined based on the use of a monoclonal antibodies, capillary zone electrophoresis and protein biomarkers

  4. Parathyroid Hormone Levels and Cognition

    Science.gov (United States)

    Burnett, J.; Smith, S.M.; Aung, K.; Dyer, C.

    2009-01-01

    Hyperparathyroidism is a well-recognized cause of impaired cognition due to hypercalcemia. However, recent studies have suggested that perhaps parathyroid hormone itself plays a role in cognition, especially executive dysfunction. The purpose of this study was to explore the relationship of parathyroid hormone levels in a study cohort of elders with impaied cognition. Methods: Sixty community-living adults, 65 years of age and older, reported to Adult Protective Services for self-neglect and 55 controls matched (on age, ethnicity, gender and socio-economic status) consented and participated in this study. The research team conducted in-home comprehensive geriatric assessments which included the Mini-mental state exam (MMSE), the 15-item geriatric depression scale (GDS) , the Wolf-Klein clock test and a comprehensive nutritional panel, which included parathyroid hormone and ionized calcium. Students t tests and linear regression analyses were performed to assess for bivariate associations. Results: Self-neglecters (M = 73.73, sd=48.4) had significantly higher PTH levels compared to controls (M =47.59, sd=28.7; t=3.59, df=98.94, plevels. Overall, PTH was correlated with the MMSE (r=-.323, p=.001). Individual regression analyses revealed a statistically significant correlation between PTH and MMSE in the self-neglect group (r=-.298, p=.024) and this remained significant after controlling for ionized calcium levels in the regression. No significant associations were revealed in the control group or among any of the other cognitive measures. Conclusion: Parathyroid hormone may be associated with cognitive performance.

  5. Parathyroid Hormone Levels and Cognition

    Science.gov (United States)

    Burnett, J.; Smith, S.M.; Aung, K.; Dyer, C.

    2009-01-01

    Hyperparathyroidism is a well-recognized cause of impaired cognition due to hypercalcemia. However, recent studies have suggested that perhaps parathyroid hormone itself plays a role in cognition, especially executive dysfunction. The purpose of this study was to explore the relationship of parathyroid hormone levels in a study cohort of elders with impaied cognition. Methods: Sixty community-living adults, 65 years of age and older, reported to Adult Protective Services for self-neglect and 55 controls matched (on age, ethnicity, gender and socio-economic status) consented and participated in this study. The research team conducted in-home comprehensive geriatric assessments which included the Mini-mental state exam (MMSE), the 15-item geriatric depression scale (GDS) , the Wolf-Klein clock test and a comprehensive nutritional panel, which included parathyroid hormone and ionized calcium. Students t tests and linear regression analyses were performed to assess for bivariate associations. Results: Self-neglecters (M = 73.73, sd=48.4) had significantly higher PTH levels compared to controls (M =47.59, sd=28.7; t=3.59, df=98.94, p<.01). There was no significant group difference in ionized calcium levels. Overall, PTH was correlated with the MMSE (r=-.323, p=.001). Individual regression analyses revealed a statistically significant correlation between PTH and MMSE in the self-neglect group (r=-.298, p=.024) and this remained significant after controlling for ionized calcium levels in the regression. No significant associations were revealed in the control group or among any of the other cognitive measures. Conclusion: Parathyroid hormone may be associated with cognitive performance.

  6. Radioiodine uptake by plants from soils

    International Nuclear Information System (INIS)

    Sabova, T.

    1976-01-01

    The uptake and accumulation of radioiodine by wheat, maize and peas from various types of soil have been studied. The uptake depends on the type of soil, on its content of organic matter and on the amount of fertilizer. Radioiodine is mainly accumulated in the roots. Accumulation in above-ground plant parts decreases in the following order: wheat, maize, peas. Uptake was highest from humus and clay soils and lowest from black and meadow soils. Application of chloride fertilizer or carrier iodine lead to an increase of radioiodine uptake in the whole plant. (author)

  7. Physiological FDG uptake in the palatine tonsils

    International Nuclear Information System (INIS)

    Kawabe, Joji; Okamura, Terue; Shakudo, Miyuki

    2001-01-01

    In clinical F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) studies of the head and neck region, remarkable symmetric tonsillar FDG uptake is sometimes observed. We determined the incidence and degree of tonsillar FDG uptake and investigated the significance of tonsillar FDG uptake. Between June 1998 and August 1998, we obtained informed consent from 17 patients who were scheduled to undergo a FDG-PET study for their own disease (11 men and 6 women; aged 22 to 77 yr) and who did not have head and neck disease to perform FDG-PET scanning of the head and neck region in addition to their target organs. The incidence and degree of tonsillar FDG uptake were determined. Remarkable tonsillar FDG uptake was found in 9 patients. The SUVs of these FDG uptakes ranged from 2.48 to 6.75, with a mean of 4.29±1.20 (SD). Tonsillar FDG uptakes in the remaining 8 patients were not remarkable, and their SUVs ranged from 1.93 to 3.31, with a mean of 2.46±0.45. Head and neck disease does not appear to have been responsible for the increase in tonsillar FDG uptake. Differences among tonsillar FDG uptake in these 17 patients without head and neck disease appear to reflect differences in activity of ''physiological'' inflammation of the palatine tonsils. (author)

  8. Normal cerebral FDG uptake during childhood

    International Nuclear Information System (INIS)

    London, Kevin; Howman-Giles, Robert

    2014-01-01

    Current understanding of cerebral FDG uptake during childhood originates from a small number of studies in patients with neurological abnormalities. Our aim was to describe cerebral FDG uptake in a dataset of FDG PET scans in children more likely to represent a normal population. We reviewed cerebral FDG PET scans in children up to 16 years of age with suspected/proven extracranial malignancies and the following exclusions: central nervous system metastases, previous malignancies, previous chemotherapy or radiotherapy, development of cerebral metastases during therapy, neurological conditions, taking antiepileptic medication or medications likely to interfere with cerebral metabolism, and general anaesthesia within 24 h. White matter, basal ganglia, thalamus and the cerebellar cortex were analysed using regional SUV max , and the cerebral cortex, basal ganglia, thalamus and cerebellum were analysed using a regional relative uptake analysis in comparison to maximal cortical uptake. Scans from 30 patients (age range 11 months to 16 years, mean age 10 years 5 months) were included. All regions showed increasing SUV max with age. The parietal, occipital, lateral temporal and medial temporal lobes showed lower rates of increasing FDG uptake causing changing patterns of regional FDG uptake during childhood. The cortical regions showing the most intense uptake in early childhood were the parietal and occipital lobes. At approximately 7 years of age these regions had relatively less uptake than the frontal lobes and at approximately 10 years of age these regions had relatively less uptake than the thalamus. Relative FDG uptake in the brain has not reached an adult pattern by 1 year of age, but continues to change up to 16 years of age. The changing pattern is due to different regional rates of increasing cortical FDG uptake, which is less rapid in the parietal, occipital and temporal lobes than in the frontal lobes. (orig.)

  9. Normal cerebral FDG uptake during childhood

    Energy Technology Data Exchange (ETDEWEB)

    London, Kevin [The Children' s Hospital at Westmead, Department of Nuclear Medicine, Sydney, NSW (Australia); University of Sydney, Discipline of Paediatrics and Child Health, Sydney Medical School, Sydney, NSW (Australia); Howman-Giles, Robert [The Children' s Hospital at Westmead, Department of Nuclear Medicine, Sydney, NSW (Australia); University of Sydney, Disciplines of Imaging and Paediatrics and Child Health, Sydney Medical School, Sydney, NSW (Australia)

    2014-04-15

    Current understanding of cerebral FDG uptake during childhood originates from a small number of studies in patients with neurological abnormalities. Our aim was to describe cerebral FDG uptake in a dataset of FDG PET scans in children more likely to represent a normal population. We reviewed cerebral FDG PET scans in children up to 16 years of age with suspected/proven extracranial malignancies and the following exclusions: central nervous system metastases, previous malignancies, previous chemotherapy or radiotherapy, development of cerebral metastases during therapy, neurological conditions, taking antiepileptic medication or medications likely to interfere with cerebral metabolism, and general anaesthesia within 24 h. White matter, basal ganglia, thalamus and the cerebellar cortex were analysed using regional SUV{sub max}, and the cerebral cortex, basal ganglia, thalamus and cerebellum were analysed using a regional relative uptake analysis in comparison to maximal cortical uptake. Scans from 30 patients (age range 11 months to 16 years, mean age 10 years 5 months) were included. All regions showed increasing SUV{sub max} with age. The parietal, occipital, lateral temporal and medial temporal lobes showed lower rates of increasing FDG uptake causing changing patterns of regional FDG uptake during childhood. The cortical regions showing the most intense uptake in early childhood were the parietal and occipital lobes. At approximately 7 years of age these regions had relatively less uptake than the frontal lobes and at approximately 10 years of age these regions had relatively less uptake than the thalamus. Relative FDG uptake in the brain has not reached an adult pattern by 1 year of age, but continues to change up to 16 years of age. The changing pattern is due to different regional rates of increasing cortical FDG uptake, which is less rapid in the parietal, occipital and temporal lobes than in the frontal lobes. (orig.)

  10. Highly potent metallopeptide analogues of luteinizing hormone-releasing hormone.

    Science.gov (United States)

    Bajusz, S; Janaky, T; Csernus, V J; Bokser, L; Fekete, M; Srkalovic, G; Redding, T W; Schally, A V

    1989-08-01

    Metal complexes related to the cytotoxic complexes cisplatin [cis-diamminedichloroplatinum(II)] and transbis(salicylaldoximato)copper(II) were incorporated into suitably modified luteinizing hormone-releasing hormone (LH-RH) analogues containing D-lysine at position 6. Some of the metallopeptides thus obtained proved to be highly active LH-RH agonists or antagonists. For instance, SB-40, a PtCl2-containing metallopeptide in which platinum is coordinated to an N epsilon-(DL-2,3-diaminopropionyl)-D-lysine residue [D-Lys(DL-A2pr] at position 6, showed 50 times higher LH-releasing potency than the native hormone. SB-95, [Ac-D-Nal(2)1,D-Phe(pCl)2, D-Pal(3)2, Arg5,D-Lys[DL-A2pr(Sal2Cu)]6,D-Ala10]LH-RH, where Nal(2) is 3-(2-naphthyl)alanine, Pal(3) is 3-(3-pyridyl)alanine, and copper(II) is coordinated to the salicylideneimino moieties resulting from condensation of salicylaldehyde with D-Lys(DL-A2pr)6, caused 100% inhibition of ovulation at a dose of 3 micrograms in rats. Most metallopeptide analogues of LH-RH showed high affinities for the membrane receptors of rat pituitary and human breast cancer cells. Some of these metallopeptides had cytotoxic activity against human breast cancer and prostate cancer cell lines in vitro (this will be the subject of a separate paper on cytotoxicity evaluation). Such cytostatic metallopeptides could be envisioned as targeted chemotherapeutic agents in cancers that contain receptors for LH-RH-like peptides.

  11. Bone uptake of Tc-99m MIBI in patients with hyperparathyroidism

    International Nuclear Information System (INIS)

    Zhao, Yunyun; Wang, Qian

    2014-01-01

    The study aimed to investigate the incidence of bone uptake of tracer on Tc-99m MIBI imaging and explore its influencing factors and significance for diagnosis of metabolic bone disease (MBD) in patients with hyperparathyroidism (HPT). Seventy-nine consecutive patients with histopathologically confirmed HPT (63 primary and 16 secondary) who had preoperative Tc-99m MIBI imaging were retrospectively evaluated. Serum calcium (Ca), phosphorus (P), and intact parathyroid hormone (iPTH) were measured for all patients, and serum alkaline phosphatase (ALP) was measured for 62 patients. Of the 79 patients, 50 underwent bone mineral density (BMD) examination and 30 underwent bone scintigraphy. The incidence and characteristics of abnormal bone uptake of MIBI were recorded. Mann-Whitney test was performed to determine if serum iPTH, Ca, P, ALP, and BMD were different between the patients with and without MIBI bone uptake. Logistic regression analysis was used to analyze the factors that influence the bone uptake of MIBI. The concordance rate between Tc-99m MIBI imaging and bone scintigraphy in delineating MBD was calculated. Tc-99m MIBI imaging disclosed the abnormal bone uptake of tracer in 22 (27.8%) patients. Of them, 19 showed diffusely increased activity in skeleton, 2 showed focal uptake in brown tumors, and one showed both above patterns. Patients with bone uptake MIBI had higher level of serum iPTH (Z=-4.34, P < 0.001) and ALP (Z=-3.50, P < 0.001) than those without bone uptake. Logistic regression analysis also showed that bone uptake of MIBI was correlated with serum iPTH (OR=4.42, P < 0.001) and ALP (OR=3.21, P=0.002). Among the 30 patients that underwent bone scintigraphy, 76.7% patients showed signs of MBD, and the concordance rate between Tc-99m MIBI imaging and bone scintigraphy was 60% for detecting MBD. Bone uptake of MIBI in patients with HPT is commonly related to a high level of iPTH and ALP; it probably reflects an active stage of MBD, and it should be

  12. Plants altering hormonal milieu: A review

    Directory of Open Access Journals (Sweden)

    Prashant Tiwari

    2017-01-01

    Full Text Available The aim of the present review article is to investigate the herbs which can alter the levels of hormones like Follicle stimulating hormone, Prolactin, Growth hormone, Insulin, Thyroxine, Estrogen, Progesterone, Testosterone, and Relaxin etc. Hormones are chemical signal agents produced by different endocrine glands for regulating our biological functions. The glands like pituitary, thyroid, adrenal, ovaries in women and testes in men all secrete a number of hormones with different actions. However, when these hormones are perfectly balanced then people become healthy and fit. But several factors like pathophysiological as well as biochemical changes, disease conditions, changes in the atmosphere, changes in the body, diet changes etc. may result in imbalance of various hormones that produce undesirable symptoms and disorders. As medicinal plants have their importance since ancient time, people have been using it in various ways as a source of medicine for regulation of hormonal imbalance. Moreover, it is observed that certain herbs have a balancing effect on hormones and have great impact on well-being of the people. So, considering these facts we expect that the article provides an overview on medicinal plants with potential of altering hormone level.

  13. Plants altering hormonal milieu: A review

    Directory of Open Access Journals (Sweden)

    Prashant Tiwari

    2017-02-01

    Full Text Available The aim of the present review article is to investigate the herbs which can alter the levels of hormones like Follicle stimulating hormone, Prolactin, Growth hormone, Insulin, Thyroxine, Estrogen, Progesterone, Testosterone, and Relaxin etc. Hormones are chemical signal agents produced by different endocrine glands for regulating our biological functions. The glands like pituitary, thyroid, adrenal, ovaries in women and testes in men all secrete a number of hormones with different actions. However, when these hormones are perfectly balanced then people become healthy and fit. But several factors like pathophysiological as well as biochemical changes, disease conditions, changes in the atmosphere, changes in the body, diet changes etc. may result in imbalance of various hormones that produce undesirable symptoms and disorders. As medicinal plants have their importance since ancient time, people have been using it in various ways as a source of medicine for regulation of hormonal imbalance. Moreover, it is observed that certain herbs have a balancing effect on hormones and have great impact on well-being of the people. So, considering these facts we expect that the article provides an overview on medicinal plants with potential of altering hormone level.

  14. Uptake of organic nitrogen by plants

    Science.gov (United States)

    Torgny Nasholm; Knut Kielland; Ulrika. Ganeteg

    2009-01-01

    Languishing for many years in the shadow of plant inorganic nitrogen (N) nutrition research, studies of organic N uptake have attracted increased attention during the last decade. The capacity of plants to acquire organic N, demonstrated in laboratory and field settings, has thereby been well established. Even so, the ecological significance of organic N uptake for...

  15. Gallium 67 uptake in thymic rebound

    International Nuclear Information System (INIS)

    Hurst, R.; Sabio, H.; Teates, C.D.

    1988-01-01

    We have reported a case of localized thymic enlargement and uptake of gallium 67 in a child who had received antineoplastic chemotherapy. The enlarged thymus showed normal histology, a picture consistent with thymic rebound after nonspecific stress. This case further demonstrates the need to consider thymic rebound as a cause of gallium 67 uptake in children with neoplastic diseases

  16. Uptake of inorganic contaminants by pteridophytes

    International Nuclear Information System (INIS)

    Zheng Jiemin; Chen Ziyuan; Tang Shirong; Guangzhou Univ., Guangzhou; Ding Bingyang

    2005-01-01

    The review covers results at home and abroad in terms of uptake of inorganic contaminants by pteridophytes, and suggests pteridophytes' significance in phytoremediation; the mechanisms related to uptake of inorganic contaminants by pteridophytes and some methods and means used for research on the mechanism are also introduced; the authors' viewpoints on future development trends are presented in this paper. (authors)

  17. Nitrogen uptake kinetics of freshly isolated zooxanthellae

    Digital Repository Service at National Institute of Oceanography (India)

    Wafar, M.V.M.; Wafar, S.; Rajkumar, R.

    that for nitrate [2.8 nmol. ( mu chl-a)./1h/1] and urea [0.37 nmol. ( mu chl-a)./1h/1]. Half-saturation constants for uptake of the three nitrogen compounds were in the range of 10-15 mu mol.l/1. Generally, uptake of any one nitrogen substrate appears to be inhibit...

  18. Radio-active iodine uptake in vitiligo

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, V.; Shankar, V.; Chaudhary, S.; Bhatia, K.K.; Mehta, L.K.; Arora, D.R. (Medical College and Hospital, Rohtak-124001 (India))

    1990-01-01

    Vitiligo and thyroid disease are commonly associated disorders. Twenty-two clinically euthyroid vitiligo patients were studied for functional assessment of thyroid by radioactive iodine uptake assay. Half of them showed abnormal uptake values at 24 hours. Of these patients, 90% had lower values indicating a tendency towards developing hypothyroid state. Subclinical thyroid dysfunction in vitiligo appears to be an adaptive change. (author).

  19. Radio-active iodine uptake in vitiligo

    International Nuclear Information System (INIS)

    Kumar, V.; Shankar, V.; Chaudhary, S.; Bhatia, K.K.; Mehta, L.K.; Arora, D.R.

    1990-01-01

    Vitiligo and thyroid disease are commonly associated disorders. Twenty-two clinically euthyroid vitiligo patients were studied for functional assessment of thyroid by radioactive iodine uptake assay. Half of them showed abnormal uptake values at 24 hours. Of these patients, 90% had lower values indicating a tendency towards developing hypothyroid state. Subclinical thyroid dysfunction in vitiligo appears to be an adaptive change. (author)

  20. 111In-labeled lactam bridge-cyclized alpha-melanocyte stimulating hormone peptide analogues for melanoma imaging.

    Science.gov (United States)

    Miao, Yubin; Gallazzi, Fabio; Guo, Haixun; Quinn, Thomas P

    2008-02-01

    The purpose of this study was to examine the influence of the lactam bridge cyclization on melanoma targeting and biodistribution properties of the radiolabeled conjugates. Two novel lactam bridge-cyclized alpha-MSH peptide analogues, DOTA-CycMSH (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-c[Lys-Nle-Glu-His-DPhe-Arg-Trp-Gly-Arg-Pro-Val-Asp]) and DOTA-GlyGlu-CycMSH (DOTA-Gly-Glu-c[Lys-Nle-Glu-His-DPhe-Arg-Trp-Gly-Arg-Pro-Val-Asp]), were synthesized and radiolabeled with (111)In. The internalization and efflux of (111)In-labeled CycMSH peptides were examined in B16/F1 melanoma cells. The melanoma targeting properties, pharmacokinetics, and SPECT/CT imaging of (111)In-labeled CycMSH peptides were determined in B16/F1 melanoma-bearing C57 mice. Both (111)In-DOTA-CycMSH and (111)In-DOTA-GlyGlu-CycMSH exhibited fast internalization and extended retention in B16/F1 cells. The tumor uptake values of (111)In-DOTA-CycMSH and (111)In-DOTA-GlyGlu-CycMSH were 9.53+/-1.41% injected dose/gram (% ID/g) and 10.40+/-1.40% ID/g at 2 h postinjection, respectively. Flank melanoma tumors were clearly visualized with (111)In-DOTA-CycMSH and (111)In-DOTA-GlyGlu-CycMSH by SPECT/CT images at 2 h postinjection. Whole-body clearance of the peptides was fast, with greater than 90% of the radioactivities cleared through urinary system by 2 h postinjection. There was low radioactivity (<0.8% ID/g) accumulated in blood and normal organs except kidneys at all time points investigated. Introduction of a negatively charged linker (-Gly-Glu-) into the peptide sequence decreased the renal uptake by 44% without affecting the tumor uptake at 4 h postinjection. High receptor-mediated melanoma uptakes coupled with fast whole-body clearance in B16/F1 melanoma-bearing C57 mice demonstrated the feasibility of using (111)In-labeled lactam bridge-cyclized alpha-MSH peptide analogues as a novel class of imaging probes for receptor-targeting melanoma imaging.

  1. Depolarization-dependent 45Ca uptake by synaptosomes of rat cerebral cortex is enhanced by L-triiodothyronine

    International Nuclear Information System (INIS)

    Mason, G.A.; Walker, C.H.; Prange, A.J. Jr.

    1990-01-01

    Depolarization-induced release of neurotransmitters and other secretions from nerve endings is triggered by the rapid entry of Ca++ through voltage-sensitive channels. Calcium entry is thought to occur in two distinct phases or processes: a fast-phase response to an action potential, which initiates release; and a slow phase associated with extended stimulation of the neuron. Thyroid hormones are sequestered by nerve terminals and can produce changes in behaviour and mood. They may therefore be involved in modulating central synaptic transmission. We studied the effects of L-triiodothyronine (T3), L-thyroxine (T4), reverse T3 (rT3) and D-T3 on depolarization-induced uptake of 45Ca by synaptosomes from euthyroid and hypothyroid rats. T3, but not T4, rT3, or D-T3 significantly enhanced depolarization-induced 45Ca uptake at physiologically relevant (1 to 10 nmol/L) concentrations. The stimulatory effect of 10 nmol/L T3 on depolarization-induced uptake after 2 seconds (21%) was greater than after 5 (10%) or 30 (8%) seconds, indicating that T3 enhanced primarily the fast-phase process. There was no effect of T3 or other hormones tested on nondepolarization-induced 45Ca uptake. Preincubation of synaptosomes with T3 prior to depolarization did not enhance the effect of T3; in fact, preincubations of 30 seconds or more resulted in diminished T3 effects. Preincubation of synaptosomes for 15 seconds with D-T3 or the addition of D-T3 and T3 together reduced the effect of T3. We found no difference in the effect of T3 on 45Ca uptake by synaptosomes from euthyroid and hypothyroid rats. These results suggest a novel mechanism of action of thyroid hormones in the brain

  2. Depolarization-dependent sup 45 Ca uptake by synaptosomes of rat cerebral cortex is enhanced by L-triiodothyronine

    Energy Technology Data Exchange (ETDEWEB)

    Mason, G.A.; Walker, C.H.; Prange, A.J. Jr. (Univ. of North Carolina, Chapel Hill (USA))

    1990-08-01

    Depolarization-induced release of neurotransmitters and other secretions from nerve endings is triggered by the rapid entry of Ca++ through voltage-sensitive channels. Calcium entry is thought to occur in two distinct phases or processes: a fast-phase response to an action potential, which initiates release; and a slow phase associated with extended stimulation of the neuron. Thyroid hormones are sequestered by nerve terminals and can produce changes in behaviour and mood. They may therefore be involved in modulating central synaptic transmission. We studied the effects of L-triiodothyronine (T3), L-thyroxine (T4), reverse T3 (rT3) and D-T3 on depolarization-induced uptake of 45Ca by synaptosomes from euthyroid and hypothyroid rats. T3, but not T4, rT3, or D-T3 significantly enhanced depolarization-induced 45Ca uptake at physiologically relevant (1 to 10 nmol/L) concentrations. The stimulatory effect of 10 nmol/L T3 on depolarization-induced uptake after 2 seconds (21%) was greater than after 5 (10%) or 30 (8%) seconds, indicating that T3 enhanced primarily the fast-phase process. There was no effect of T3 or other hormones tested on nondepolarization-induced 45Ca uptake. Preincubation of synaptosomes with T3 prior to depolarization did not enhance the effect of T3; in fact, preincubations of 30 seconds or more resulted in diminished T3 effects. Preincubation of synaptosomes for 15 seconds with D-T3 or the addition of D-T3 and T3 together reduced the effect of T3. We found no difference in the effect of T3 on 45Ca uptake by synaptosomes from euthyroid and hypothyroid rats. These results suggest a novel mechanism of action of thyroid hormones in the brain.

  3. Uptake and transport of chromium in plants

    International Nuclear Information System (INIS)

    Ramachandran, V.; D'souza, T.J.; Mistry, K.B.

    1980-01-01

    The uptake of chromium, an important soil and water pollutant, by five different plant species was examined in nutrient culture experiments using chromium-51 as a tracer. The concentration in aerial tissues of both trivalent and hexavalent forms of chromium was the greatest in peas followed by beans, tomato and the cereals over identical uptake periods. The uptake of 51 Cr 3+ was, in general, greater than 51 CrO 4 2- . Studies with bean plants indicated that shoot uptake of both forms of chromium decreased with increasing pH and salt concentration of the external solution. Concentrations of 10 -4 M and 10 -5 M DNP inhibited 51 Cr uptake by bean shoots. (author)

  4. Insulin resistance and maximal oxygen uptake

    DEFF Research Database (Denmark)

    Seibaek, Marie; Vestergaard, Henrik; Burchardt, Hans

    2003-01-01

    BACKGROUND: Type 2 diabetes, coronary atherosclerosis, and physical fitness all correlate with insulin resistance, but the relative importance of each component is unknown. HYPOTHESIS: This study was undertaken to determine the relationship between insulin resistance, maximal oxygen uptake......, and the presence of either diabetes or ischemic heart disease. METHODS: The study population comprised 33 patients with and without diabetes and ischemic heart disease. Insulin resistance was measured by a hyperinsulinemic euglycemic clamp; maximal oxygen uptake was measured during a bicycle exercise test. RESULTS......: There was a strong correlation between maximal oxygen uptake and insulin-stimulated glucose uptake (r = 0.7, p = 0.001), and maximal oxygen uptake was the only factor of importance for determining insulin sensitivity in a model, which also included the presence of diabetes and ischemic heart disease. CONCLUSION...

  5. Corticotropin-releasing hormone and mast cells in the regulation of mucosal barrier function in the human colon.

    Science.gov (United States)

    Wallon, Conny; Söderholm, Johan D

    2009-05-01

    Corticotropin-releasing hormone (CRH) is an important neuro-endocrine mediator of the stress response. Local effects of CRH in the intestinal mucosa have become evident in recent years. We showed that CRH activates CRH receptor subtypes R1 and R2 on subepithelial mast cells, thereby inducing increased transcellular uptake of protein antigens in human colonic biopsies in Ussing chambers. Ongoing studies also implicate local cholinergic signaling in regulation of macromolecular permeability in the human colon. Since increased uptake of antigenic molecules is associated with mucosal inflammation, our findings may have implications for understanding stress-related intestinal disorders.

  6. Effect of growth hormone replacement therapy on pituitary hormone secretion and hormone replacement therapies in GHD adults

    DEFF Research Database (Denmark)

    Hubina, Erika; Mersebach, Henriette; Rasmussen, Ase Krogh

    2004-01-01

    We tested the impact of commencement of GH replacement therapy in GH-deficient (GHD) adults on the circulating levels of other anterior pituitary and peripheral hormones and the need for re-evaluation of other hormone replacement therapies, especially the need for dose changes.......We tested the impact of commencement of GH replacement therapy in GH-deficient (GHD) adults on the circulating levels of other anterior pituitary and peripheral hormones and the need for re-evaluation of other hormone replacement therapies, especially the need for dose changes....

  7. Factors influencing the uptake of {sup 18}F-fluoroestradiol in patients with estrogen receptor positive breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Peterson, Lanell M. [Department of Radiology, University of Washington Medical Center, Seattle WA (United States); Department of Radiology, Seattle Cancer Care Alliance, Seattle WA (United States); Kurland, Brenda F. [Clinical Division, Fred Hutchinson Cancer Research Center, Seattle, WA (United States); Link, Jeanne M. [Department of Radiology, University of Washington Medical Center, Seattle WA (United States); Schubert, Erin K. [Department of Radiology, University of Washington Medical Center, Seattle WA (United States); Department of Radiology, Seattle Cancer Care Alliance, Seattle WA (United States); Stekhova, Svetlana [Department of Radiology, University of Washington Medical Center, Seattle WA (United States); Linden, Hannah M. [Department of Medical Oncology, University of Washington Medical Center/Seattle Cancer Care Alliance, Seattle, WA (United States); Mankoff, David A., E-mail: dam@u.washington.edu [Department of Radiology, University of Washington Medical Center, Seattle WA (United States); Department of Radiology, Seattle Cancer Care Alliance, Seattle WA (United States)

    2011-10-15

    Introduction: {sup 18}F-Fluoroestradiol (FES) PET imaging provides a non-invasive method to measure estrogen receptor (ER) expression in tumors. Assessment of factors that could affect the quantitative level of FES uptake is important as part of the validation of FES PET for evaluating regional ER expression in breast cancer. Methods: This study examines FES uptake in tumors from 312 FES PET scans (239 patients) with documented ER+ primary breast cancer. FES uptake was compared to clinical and laboratory data, treatment prior to or at time of scan, and properties of FES and its metabolism and transport. Linear mixed models were used to explore univariate, threshold-based and multivariate associations. Results: Sex hormone-binding globulin (SHBG) was inversely associated with FES SUV. Average FES uptake did not differ by levels of plasma estradiol, age or rate of FES metabolism. FES tumor uptake was greater for patients with a higher body mass index (BMI), but this effect did not persist when SUV was corrected for lean body mass (LBM). In multivariate analysis, only plasma SHBG binding was an independent predictor of LBM-adjusted FES SUV. Conclusions: Calculation of FES SUV, possibly adjusted for LBM, should be sufficient to assess FES uptake for the purpose of inferring ER expression. Pre-menopausal estradiol levels do not appear to interfere with FES uptake. The availability and binding properties of SHBG influence FES uptake and should be measured. Specific activity did not have a clear influence on FES uptake, except perhaps at higher injected mass per kilogram. These results suggest that FES imaging protocols may be simplified without sacrificing the validity of the results.

  8. The thyroid hormone, parathyroid hormone and vitamin D associated hypertension

    Directory of Open Access Journals (Sweden)

    Sandeep Chopra

    2011-01-01

    Full Text Available Thyroid disorders and primary hyperparathyroidism have been known to be associated with increases in blood pressure. The hypertension related to hypothyroidism is a result of increased peripheral resistance, changes in renal hemodynamics, hormonal changes and obesity. Treatment of hypothyroidism with levo-thyroxine replacement causes a decrease in blood pressure and an overall decline in cardiovascular risk. High blood pressure has also been noted in patients with subclinical hypothyroidism. Hyperthyroidism, on the other hand, is associated with systolic hypertension resulting from an expansion of the circulating blood volume and increase in stroke volume. Increased serum calcium levels associated with a primary increase in parathyroid hormone levels have been also associated with high blood pressure recordings. The mechanism for this is not clear but the theories include an increase in the activity of the renin-angiotensin-aldosterone system and vasoconstriction. Treatment of primary hyperparathyroidism by surgery results in a decline in blood pressure and a decrease in the plasma renin activity. Finally, this review also looks at more recent evidence linking hypovitaminosis D with cardiovascular risk factors, particularly hypertension, and the postulated mechanisms linking the two.

  9. Thyroid hormone metabolism in poultry

    Directory of Open Access Journals (Sweden)

    Darras V.M.

    2000-01-01

    Full Text Available Thyroid hormone (TH receptors preferentially bind 3.5,3'-triiodothyronine (T3. Therefore the metabolism of thyroxine (T4 secreted by the thyroid gland in peripheral tissues, resulting in the production and degradation of receptor-active T3, plays a major role in thyroid function. The most important metabolic pathway for THs is deiodination. Another important pathway is sulfation, which is a reversible pathway that has been shown to interact with TH deiodination efficiency. The enzymes catalysing TH deiodination consist of three types. Type 1 deiodinase (D1 catalyses both outer ring (ORD and inner ring deiodinalion (IRD. Type II deiodinase (D2 only catalyses ORD while type III (D3 only catalyses IRD. The three chicken deiodinase cDNAs have been cloned recently. These enzymes all belong to the family of selenoproteins. Ontogenetic studies show that the availability of deiodinases is regulated in a tissue specific and developmental stage dependent way. Characteristic for the chicken is the presence of very high levels off, inactivating D3 enzyme in the embryonic liver. Hepatic D3 is subject to acute regulation in a number of situations. Both growth hormone and glucocorticoid injection rapidly decrease hepatic D3 levels, hereby increasing plasma T3 without affecting hepatic D1 levels. The inhibition of D3 seems to be regulated mainly at the level of D3 gene transcription. The effect of growth hormone on D3 expression persists throughout life, while glucocorticoids start to inhibit hepatic D1 expression in posthatch chickens. Food restriction in growing chickens increases hepatic D3 levels. This contributes to the decrease in plasma T3 necessary to reduce energy loss. Refeeding restores hepatic D3 and plasma T3 to control levels within a few hours. It can be concluded that the tissue and time dependent regulation of the balance between TH activating and inactivating enzymes plays an essential role in the control of local T3 availability and hence in

  10. Association of Hormonal Contraception With Depression

    DEFF Research Database (Denmark)

    Skovlund, Charlotte Wessel; Mørch, Lina Steinrud; Kessing, Lars Vedel

    2016-01-01

    to those who never used hormonal contraception, the RR estimates for users of combined oral contraceptives increased to 1.7 (95% CI, 1.66-1.71). Conclusions and Relevance: Use of hormonal contraception, especially among adolescents, was associated with subsequent use of antidepressants and a first......Importance: Millions of women worldwide use hormonal contraception. Despite the clinical evidence of an influence of hormonal contraception on some women's mood, associations between the use of hormonal contraception and mood disturbances remain inadequately addressed. Objective: To investigate...... whether the use of hormonal contraception is positively associated with subsequent use of antidepressants and a diagnosis of depression at a psychiatric hospital. Design, Setting, and Participants: This nationwide prospective cohort study combined data from the National Prescription Register...

  11. Free thyroid hormones in health and disease

    International Nuclear Information System (INIS)

    Bueber, V.

    1984-01-01

    Several groups of patients with normal and abnormal thyroid function as well as patients with goitre on hormone substitution are discussed with respect to the diagnostic value of the free thyroid hormone methods. The free T 3 technique under investigation separates clearly between euthyroidism and hyperthyroidism, however, during application of contraceptive pills and during pregnancy free T 3 is slightly enhanced. Free T 4 can be found in the normal range even in hypothyroidism, during T 4 substitution free T 4 is useful for control of adequate hormone substitution. Free thyroid hormones are advantageous to be performed with respect to practicability compared to the estimation of total hormone concentrations by enzyme as well as radioimmunoassay. Normally there is no additional demand for measurement of thyroid hormone binding proteins, another rather economical argument for using these parameters in thyroid diagnosis. (orig.) [de

  12. Anticoncepción hormonal

    Directory of Open Access Journals (Sweden)

    Miguel Lugones Botell

    1997-02-01

    Full Text Available Se realizó una revisión de los anticonceptivos hormonales con énfasis en aspectos que van desde su descubrimiento, el mecanismo de acción, los diferentes tipos y formas de utilización, así como el esquema de administración terapéutica en algunas entidades, sus indicaciones, ventajas y contraindicaciones: A review of the hormonal contraceptives was carried out, emphasizing on features from their discovery, trigger mechanism, different kinds, and ways to use them, as well as the scheme of the therapeutical administration in some entities, its indications, advantages, and contraindications.

  13. Inhibitors of plant hormone transport

    Czech Academy of Sciences Publication Activity Database

    Klíma, Petr; Laňková, Martina; Zažímalová, Eva

    2016-01-01

    Roč. 253, č. 6 (2016), s. 1391-1404 ISSN 0033-183X R&D Projects: GA MŠk(CZ) LD15088 Institutional support: RVO:61389030 Keywords : polar auxin transport * acid-binding protein * gnom arf-gef * equilibrative nucleoside transporter * efflux carrier polarity * plasma-membrane-protein * cultured tobacco cells * arabidopsis-thaliana * gravitropic response * brefeldin-a * Plant hormones * Transport * Inhibitors * Auxin * Cytokinins * Strigolactones * Abscisic acid * Cell biology Subject RIV: ED - Physiology Impact factor: 2.870, year: 2016

  14. Thyroid hormones and cardiac arrhythmias

    Czech Academy of Sciences Publication Activity Database

    Tribulová, N.; Knezl, V.; Shainberg, A.; Seki, S.; Soukup, Tomáš

    2010-01-01

    Roč. 52, 3-4 (2010), s. 102-112 ISSN 1537-1891 R&D Projects: GA ČR(CZ) GA304/08/0256 Grant - others:VEGA(SK) 2/0049/09; APVV(SK) 51-059505; APVV(SK) 51-017905 Institutional research plan: CEZ:AV0Z50110509 Keywords : thyroid hormone * arrhythmias * ion channels * connexin-43 Subject RIV: FA - Cardiovascular Disease s incl. Cardiotharic Surgery Impact factor: 2.174, year: 2010

  15. Some biological properties of human chorionic follicle stimulating hormone

    International Nuclear Information System (INIS)

    Tojo, Shimpei; Ashitaka, Yoshihiko; Maruo, Takeshi; Nishimoto, Hiroyuki

    1975-01-01

    The biological properties of human chorionic FSH (hCFSH) for rat ovaries were investigated. Highly purified hCFSH had similar response to the ovarian augmentation test as bovine FSH and significantly enhanced 3 H-thymidine uptake by granulosa cells and theca cells in the ovary of hypophysectomized rat. In contrast, highly purified hCG little responded to the ovarian augmentation test and had no effect on 3 H-thymidine uptake by the ovary. These results indicate that hCFSH may promote the follicular growth of ovary resulting from granulosa cell proliferation and its enlargement. In addition, freshly harvested porcine granulosa cells were employed in an in vitro system to investigate specific binding of hCFSH to ovarian receptor. Radioiodinated hCFSH ( 125 I-hCFSH) and hCG ( 125 I-hCG) were respectively incubated with cell suspensions. Binding of these hormone preparations was proportional to the cell number and increased with the time of incubation through 120 minutes. The binding ability of 125 I-hCFSH to the cells was greater than that of 125 I-hCG. Increasing concentrations of unlabeled hCFSH in the incubation mixture progressively inhibited the uptake of 125 I-hCFSH by granulosa cells. Unlabeled hCG was not able to compete with 125 I-hCFSH binding. The similar phenomenon to inhibit the binding of 125 I-hCG to the cells was also recognized in the presence of unlabeled hCG. These findings suggest that granulosa cell has at least two different types of receptor sites: one for hCFSH and the other for hCG. (auth.)

  16. Cellular uptake of lipoproteins and Persistent Organic Compounds - An update and new data

    DEFF Research Database (Denmark)

    Hjelmborg, Philip Sebastian; Andreassen, Thomas Kjærgaard; Bonefeld-Jørgensen, Eva Cecilie

    2008-01-01

    including the pesticide DDT (p,p'-dichlorodiphenyltrichloroethane), and especially its metabolite DDE (p,p'-dichlorodiphenyldichloroethene), interacts with nuclear hormone receptors causing these to malfunction, which in turn results in a range of deleterious health effects in humans. The aim of the present...... study was to determine the role of lipoprotein receptors in mouse embryonic fibroblast (MEF) cells in conjunction with uptake of DDT-lipoprotein complexes from supplemented media in vitro. Uptake of DDT by MEF cells was investigated using MEF1 cells carrying the receptors LRP (low-density lipoprotein...... receptor-related protein) and LDLR (low density lipoprotein receptor) present and MEF4 cells with no LRP and LDLR expression. Cells were incubated together with the complex of LDL and [14C]DDT. The receptor function was further evaluated by adding the 40 kDa receptor-associated protein (RAP) which blocks...

  17. Determination of maximum physiologic thyroid uptake and correlation with 24-hour RAI uptake value

    International Nuclear Information System (INIS)

    Duldulao, M.; Obaldo, J.

    2007-01-01

    Full text: In hyperthyroid patients, thyroid uptake values are overestimated, sometimes approaching or exceeding 100%. This is physiologically and mathematically impossible. This study was undertaken to determine the maximum physiologic thyroid uptake value through a proposed simple method using a gamma camera. Methodology: Twenty-two patients (17 females and 5 males), with ages ranging from 19-61 y/o (mean age ± SD; 41 ± 12), with 24-hour uptake value of >50%, clinically hyperthyroid and referred for subsequent radioactive iodine therapy were studied. The computed maximum physiologic thyroid uptake was compared with the 24-hour uptake using the paired Student t-test and evaluated using linear regression analysis. Results: The computed physiologic uptake correlated poorly with the 24-hour uptake value. However, in the male subgroup, there was no statistically significant difference between the two (p=0.77). Linear regression analysis gives the following relationship: physiologic uptake (%) = 77.76 - 0.284 (24-hour RAI uptake value). Conclusion: Provided that proper regions of interest are applied with correct attenuation and background subtraction, determination of physiologic thyroid uptake may be obtained using the proposed method. This simple method may be useful prior to I-131 therapy for hyperthyroidism especially when a single uptake determination is performed. (author)

  18. Postpartum thyrotoxicosis in a patient with Graves' disease. Association with low radioactive iodine uptake

    International Nuclear Information System (INIS)

    Eckel, R.H.; Green, W.L.

    1980-01-01

    A patient with previously diagnosed Graves' hyperthyroidism had a transient episode of thyrotoxicosis three months postpartum. This was associated with a diffusely enlarged thyroid gland, a rise in antithyroid microsomal antibody titer, a 24-hour radioactive iodine uptake (RAIU) of 1%, and an aspiration biopsy specimen suggestive of chronic lymphocytic thyroiditis. An alternative cause for the depressed RAIU was not discovered. This case would suggest that patients with previously diagnosed Graves' disease can have thyrotoxicosis without an enhanced RAIU and that the postpartum thyrotoxin syndrome may involve an immunologic injury causing a release of performed thyroid hormone

  19. GLP-1 increases microvascular recruitment but not glucose uptake in human and rat skeletal muscle

    DEFF Research Database (Denmark)

    Sjøberg, Kim Anker; Holst, Jens Juul; Rattigan, Stephen

    2014-01-01

    The insulinotropic gut hormone, glucagon-like-peptide-1 (GLP-1) has been proposed to have effects on vascular function and glucose disposal. However, whether GLP-1 is able to increase microvascular recruitment (MVR) in humans has not been investigated. GLP-1 was infused in the femoral artery...... in overnight fasted healthy young men. Microvascular recruitment was measured with real time contrast-enhanced ultrasound and leg glucose uptake by the leg balance technique with and without inhibition of the insulinotropic response of GLP-1 by co-infusion of octreotide. As a positive control, MVR and leg...

  20. Growth hormone insensitivity syndrome: A sensitive approach

    Directory of Open Access Journals (Sweden)

    Soumik Goswami

    2012-01-01

    Full Text Available Patients with Growth Hormone Insensitivity have characteristic phenotypic features and severe short stature. The underlying basis are mutations in the growth hormone receptor gene which gives rise to a characteristic hormonal profile. Although a scoring system has been devised for the diagnosis of this disorder, it has not been indisputably validated. The massive expense incurred in the diagnosis and treatment of this condition with suboptimal therapeutic response necessitates a judicious approach in this regard in our country.