scholarly journals Somatostatinergic ligands in dopamine-sensitive and -resistant prolactinomas

2008 ◽  
Vol 158 (5) ◽  
pp. 595-603 ◽  
Author(s):  
Alessandra Fusco ◽  
Ginette Gunz ◽  
Philippe Jaquet ◽  
Henry Dufour ◽  
Anne Laure Germanetti ◽  
...  
Keyword(s):  
Thymidine Incorporation ◽  
Primary Cultures ◽  
Receptor Subtypes ◽  
Mrna Levels ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
The Mean ◽  
Design And Methods ◽  
Dose Dependent ◽  
Receptor Mrnas

ObjectiveTen percent of patients with prolactinoma fail to respond with normalization of prolactin (PRL) and tumor shrinkage under dopamine agonist (DA) therapy. The resistance to treatment is linked to a loss of dopamine receptor 2 (D2DR). Prolactinomas express somatostatin (SST) receptor subtypes, SSTR1, 2, and 5. The aim of this study was to determine whether different SST compounds could overcome the resistance to DA in prolactinomas.Design and methodsThe efficacy of SSTR1, SSTR2, and SSTR5 ligands; the universal SST ligand, SOM230; and the chimeric SST-DA compound, BIM-23A760, was compared with cabergoline in suppressing PRL secretion from primary cultures of ten prolactinomas (six DA responders and four DA resistant). Receptor mRNAs were assessed by quantitative PCR.ResultsThe mean mRNA levels for D2DR, SSTR1, SSTR2, and SSTR5 were 92.3±47.3, 2.2±1.4, 1.1±0.7, and 1.6±0.6 copy/copy β-glucuronidase (β-Gus) respectively. The SSTR1 agonist, BIM-23926, did not suppress PRL in prolactinomas. In a DA-resistant prolactinoma, it did not inhibit [3H]thymidine incorporation. The SSTR5 compound, BIM-23206, produced a dose-dependent inhibition of PRL release similar to that of cabergoline in three DA-sensitive prolactinomas. BIM-23A760 produced a maximal PRL inhibition superimposable to that obtained with cabergoline with a lower EC50 (0.5±0.1 vs 2.5±1.5 pmol/l). In DA-resistant prolactinomas, BIM-23206 and SOM230 were ineffective. Cabergoline and BIM-23A760 produced a partial inhibition of PRL secretion (19±6 and 21±3% respectively).ConclusionAlthough the SSTRs are expressed in prolactinomas, the somatostatinergic ligands analyzed do not appear to be highly effective in suppressing PRL. D2DR remains the primary target for effective treatment of prolactinomas.

μ-Opiate Receptors in Neuronal Primary Cultures from Cerebral Cortex

1990 ◽  
Vol 17 (3) ◽  
pp. 177-181
Author(s):  
Peter S. Eriksson ◽  
Elisabeth Hansson ◽  
Lars Rönnbäck
Keyword(s):  
Cerebral Cortex ◽  
Primary Cultures ◽  
Opiate Receptors ◽  
Neuronal Cultures ◽  
Camp Accumulation ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
Neuronal Primary Cultures ◽  
Dose Dependent ◽  
Μ Receptor

The presence of μ-opioid receptors was demonstrated as effects of receptor stimulation on PGE1-induced cAMP accumulation in neuronal-enriched primary cultures from rat cerebral cortex. Morphine was used as a μ-receptor agonist. There was a dose-dependent inhibition of the PGE1-stimulated cAMP accumulation by morphine, blocked by the μ-receptor antagonist naloxone. These findings suggest that these neuronal cultures express μ-receptors, possibly connected to adenylate cyclase via an inhibitory Gi-protein. The probable use of functional μ-receptors in neurotoxicological tests is discussed.

scholarly journals In vitro impact of pegvisomant on growth hormone-secreting pituitary adenoma cells

2016 ◽  
Vol 23 (7) ◽  
pp. 509-519 ◽  
Author(s):  
Thomas Cuny ◽  
Caroline Zeiller ◽  
Martin Bidlingmaier ◽  
Céline Défilles ◽  
Catherine Roche ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Cell Line ◽  
Primary Cultures ◽  
Somatostatin Analogs ◽  
Primary Tumors ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
The Impact ◽  
Dose Dependent

Pegvisomant (PEG), an antagonist of growth hormone (GH)-receptor (GHR), normalizes insulin-like growth factor 1 (IGF1) oversecretion in most acromegalic patients unresponsive to somatostatin analogs (SSAs) and/or uncontrolled by transsphenoidal surgery. The residual GH-secreting tumor is therefore exposed to the action of circulating PEG. However, the biological effect of PEG at the pituitary level remains unknown. To assess the impact of PEG in vitro on the hormonal secretion (GH and prolactin (PRL)), proliferation and cellular viability of eight human GH-secreting tumors in primary cultures and of the rat somatolactotroph cell line GH4C1. We found that the mRNA expression levels of GHR were characterized in 31 human GH-secreting adenomas (0.086 copy/copy β-Gus) and the GHR was identified by immunocytochemistry staining. In 5/8 adenomas, a dose-dependent inhibition of GH secretion was observed under PEG with a maximum of 38.2±17% at 1μg/mL (P<0.0001 vs control). A dose-dependent inhibition of PRL secretion occurred in three mixed GH/PRL adenomas under PEG with a maximum of 52.8±11.5% at 10μg/mL (P<0.0001 vs control). No impact on proliferation of either human primary tumors or GH4C1 cell line was observed. We conclude that PEG inhibits the secretion of GH and PRL in primary cultures of human GH(/PRL)-secreting pituitary adenomas without effect on cell viability or cell proliferation.

Stimulation of endothelial cell proliferation by FGF-2 in the presence of fibrinogen requires αvβ3

Blood ◽  
2004 ◽  
Vol 104 (12) ◽  
pp. 3635-3641 ◽  
Author(s):  
Abha Sahni ◽  
Charles W. Francis
Keyword(s):  
Endothelial Cell ◽  
Thymidine Incorporation ◽  
Endothelial Cell Proliferation ◽  
Fgf Receptor ◽  
Inhibition Of Proliferation ◽  
Fibrinogen Binding ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
Specific Association ◽  
Dose Dependent

We have shown previously that fibrin(ogen) binding potentiates the capacity of fibroblast growth factor 2 (FGF-2) to stimulate endothelial cell (EC) proliferation. We have now investigated the receptor requirement for EC proliferation by fibrinogen-bound FGF-2. ECs were cultured with 25 ng/mL FGF-2 with or without 10 μg/mL fibrinogen, and proliferation was measured as 3H-thymidine incorporation. Proliferation was increased 2.4 ± 0.5-fold over medium alone with FGF-2 and increased significantly more to 4.0 ± 0.7-fold with fibrinogen and FGF-2 (P &lt; .005). Addition of 7E3 or LM609, antibodies to αvβ3, inhibited EC proliferation with fibrinogen-bound FGF-2 by 80% ± 8% (P &lt; .001) or 67% ± 14% (P &lt; .002), respectively, to levels significantly less than that observed with FGF-2 alone (P &lt; .001). Neither LM609 nor 7E3 exhibited any inhibition of activity with FGF-2 alone. Peptide GRGDS caused dose-dependent inhibition of proliferation by fibrinogen-bound FGF-2 of 31% ± 8%, 45% ± 9%, and 68% ± 11% at 0.25, 0.5, and 1 mM, respectively. Coimmunoprecipitation and immunofluorescence studies demonstrated a direct specific association between αvβ3 and FGF receptor 1 (FGFR1) in ECs and fibroblasts when exposed to both FGF-2 and fibrinogen but not with vitronectin. We conclude that fibrinogen binding of FGF-2 enhances EC proliferation through the coordinated effects of colocalized αvβ3 and FGFR1.

Endotoxin Inhibits Prostacyclin Release From Rabbit Aorta

1981 ◽  
Author(s):  
J Zahavi ◽  
A C Honey ◽  
J Westwick ◽  
V V Kakkar
Keyword(s):  
Platelet Aggregation ◽  
Rabbit Aorta ◽  
Inhibitory Effect ◽  
White Female ◽  
Time Intervals ◽  
E Coli ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
The Mean ◽  
Dose Dependent

Released prostacyclin (PGI2) activity has been studied in aortic rings of 19 New Zealand white female rabbits. These rings produced a potent inhibitor of platelet aggregation, identified as PGI2. All the rabbits were anaesthetized with pentobarbital and thereafter a solution of endotoxin (E. Coli, 0111, B4, Difco Lab.) was injected intravenously to 7 rabbits (304μg/kg every 15 min during 1 hour to achieve an estimated plasma level of 1-2 μg/ml). Another 5 rabbits served as controls and were injected with saline. After 1 hour the aorta was rapidly excised, cleaned, cut into small rings and the released PGI2 activity studied at various time intervals (5-30 min) at 37°C. The mean release of PGI2 (in pg/mg wet tissue) in the control rabbits was 201 (range 50-443). It decreased significantly to 104 (range 0-237) after 30 min. In the endotoxaemic rabbits, the initial PGI2 release was only 73 (range 0-329) (p<0,008 compared to control rabbits). This level did not change with time and was 71.9 (range 0-261) after 30 min suggesting that the “endotoxinemic” vessels were initially relatively exhausted and were not able to release PGI2. In the remaining 7 rabbits the aorta was removed immediately after anaesthesia and aortic rings incubated for 5-30 min Krebs-Henleit buffer or endotoxin 0.2-10 μg/ml and the released PGI2 activity studied. There was a dose dependent inhibition which was more pronounced after 30 min incubation.The decrease in PGI2 release from rabbit aorta following endotoxaemia removes the inhibitory effect on platelet aggregation of the arterial vessel wall and consequently may contribute to the development of a thrombogenic state.

Differences between antigenic determinants of pig and cat zona pellucida proteins

Reproduction ◽  
2000 ◽  
pp. 15-23 ◽  
Author(s):  
K Jewgenow ◽  
M Rohleder ◽  
I Wegner
Keyword(s):  
In Vitro Fertilization ◽  
Zona Pellucida ◽  
Antigenic Determinants ◽  
Vitro Fertilization ◽  
Contraceptive Vaccine ◽  
Sperm Binding ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
Dose Dependent

Despite many efforts, the control of reproduction in feral cat populations is still a problem in urban regions around the world. Immunocontraception is a promising approach; thus the present study examined the suitability of the widely used pig zona pellucida proteins (pZP) for contraception in feral domestic cats. Purified zona pellucida proteins obtained from pig and cat ovaries were used to produce highly specific antisera in rabbits. Antibodies against pZP raised in rabbits or lions were not effective inhibitors of either in vitro sperm binding (cat spermatozoa to cat oocytes) or in vitro fertilization in cats, whereas antibodies against feline zona pellucida proteins (fZP) raised in rabbits showed a dose-dependent inhibition of in vitro fertilization. Immunoelectrophoresis, ELISA and immunohistology of ovaries confirmed these results, showing crossreactivity of anti-fZP sera to fZP and to a lesser extent to pZP, but no interaction of anti-pZP sera with fZP. It is concluded that cat and pig zonae pellucidae express a very small number of shared antigenic determinants, making the use of pZP vaccine in cats questionable. A contraceptive vaccine based on feline zona pellucida determinants will be a better choice for the control of reproduction in feral cats if immunogenity can be achieved.

Antioxidant effects and in vitro cytotoxicity on human cancer cell lines of flavonoid-rich Flamboyant (Delonix regia (Bojer) Raf.) flower extract

2020 ◽  
Vol 21 ◽  
Author(s):  
Putthiporn Khongkaew ◽  
Phanphen Wattanaarsakit ◽  
Konstantinos I. Papadopoulos ◽  
Watcharaphong Chaemsawang
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Leukemia Cell ◽  
Leukemia Cell Line ◽  
Flower Extract ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
Murine Leukemia Cell ◽  
Dose Dependent

Background: Cancer is a noncommunicable disease with increasing incidence and mortality rates both worldwide and in Thailand. Its apparent lack of effective treatments is posing challenging public health issues. Introduction: Encouraging research results indicating probable anti-cancer properties of the Delonix regia flower extract (DRE) have prompted us to evaluate the feasibility of developing a type of product for future cancer prevention or treatment. Methods and Results: In the present report, using High Performance Liquid Chromatography (HPLC), we demonstrate in the DRE, the presence of high concentrations of three identifiable flavonoids, namely rutin 4.15±0.30 % w/w, isoquercitrin 3.04±0.02 %w/w, and myricetin 2.61±0.01 % w/w respectively while the IC50 of DPPH and ABTS assay antioxidation activity was 66.88±6.30 µg/ml and 53.65±7.24 µg/ml respectively. Discussion: Our cancer cell line studies using the MTT assay demonstrated DREs potent and dose dependent inhibition of murine leukemia cell line (P-388: 35.28±4.07% of cell viability remaining), as well as of human breast adenocarcinoma (MCF-7), human cervical carcinoma (HeLa), human oral cavity carcinoma (KB), and human colon carcinoma (HT-29) cell lines in that order of magnitude. Conclusion: Three identifiable flavonoids (rutin, isoquercitrin and myricetin) with high antioxidation activity and potent and dose dependent inhibition of murine leukemia cell line and five other cancer cell lines were documented in the DRE. The extract’s lack of cytotoxicity in 3 normal cell lines is a rare advantage not usually seen in current antineoplastic agents. Yet another challenge of the DRE was its low dissolution rate and long-term storage stability, issues to be resolved before a future product can be formulated.

Investigation on the antibacterial activity of electronic cigarette liquids (ECLs): a proof of concept study

2020 ◽  
Vol 21 ◽  
Author(s):  
Virginia Fuochi ◽  
Massimo Caruso ◽  
Rosalia Emma ◽  
Aldo Stivala ◽  
Riccardo Polosa ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Bacterial Species ◽  
A549 Cells ◽  
Bactericidal Effect ◽  
Minimal Bactericidal Concentration ◽  
Viability Assay ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
Dose Dependent

Background: The key ingredients of e-cigarettes liquid are commonly propane-1,2-diol (also called propylene glycol) and propane-1,2,3-triol (vegetal glycerol) and their antimicrobial effects are already established. The nicotine and flavors which are often present in e-liquids can interfere with the growth of some microorganisms. Objective: The effect of the combining these elements in e-liquids is unknown. The aim of the study was to investigate the possible effects of these liquids on bacterial growth in the presence or absence of nicotine and flavors. Methods: Susceptibilities of pathogenic strains (Klebsiella pneumoniae, Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii, Escherichia coli, Enterococcus faecalis and Sarcina lutea) were studied by means of a multidisciplinary approach. Cell viability and antioxidant assays were also evaluated. Results: All e-liquids investigated showed antibacterial activity against at least one pathogenic strain. A higher activity was correlated to the presence of flavors and nicotine. Discussion: In most cases the value of minimal bactericidal concentration is equal to the value of minimal inhibitory concentration showing that these substances have a bactericidal effect. This effect was observed in concentrations up to 6.25% v/v. Antioxidant activity was also correlated to presence of flavors. Over time, the viability assay in human epithelial lung A549 cells showed a dose-dependent inhibition of cell growth. Conclusion: Our results have shown that flavors considerably enhance the antibacterial activity of propane-1,2-diol and propane-1,2,3-triol. This study provides important evidence that should be taken into consideration in further investigative approaches, to clarify the different sensitivity of the various bacterial species to e-liquids, including the respiratory microbiota, to highlight the possible role of flavors and nicotine.

scholarly journals In VitroActivities of Hexaazatrinaphthylenes against Leishmania spp.

2015 ◽  
Vol 59 (5) ◽  
pp. 2867-2874 ◽  
Author(s):  
Atteneri López-Arencibia ◽  
Daniel García-Velázquez ◽  
Carmen M. Martín-Navarro ◽  
Ines Sifaoui ◽  
María Reyes-Batlle ◽  
...  
Keyword(s):  
Therapeutic Agents ◽  
Content Type ◽  
Inhibition Effect ◽  
Intracellular Amastigotes ◽  
Dependent Inhibition ◽  
Leishmania Spp ◽  
Dose Dependent Inhibition ◽  
Dose Dependent ◽  
Potential Use

ABSTRACTThein vitroactivity of a novel group of compounds, hexaazatrinaphthylene derivatives, against two species ofLeishmaniais described in this study. These compounds showed a significant dose-dependent inhibition effect on the proliferation of the parasites, with 50% inhibitory concentrations (IC50s) ranging from 1.23 to 25.05 μM against the promastigote stage and 0.5 to 0.7 μM against intracellular amastigotes. Also, a cytotoxicity assay was carried out to in order to evaluate the possible toxic effects of these compounds. Moreover, different assays were performed to determine the type of cell death induced after incubation with these compounds. The obtained results highlight the potential use of hexaazatrinaphthylene derivatives againstLeishmaniaspecies, and further studies should be undertaken to establish them as novel leishmanicidal therapeutic agents.

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