Modification by Su-10'603 of the response to histamine on the production of cortisol and corticosterone in isolated canine adrenocortical cells

1982 ◽  
Vol 101 (4) ◽  
pp. 586-591 ◽  
Author(s):  
T. Hirose ◽  
I. Matsumoto ◽  
T. Aikawa
Keyword(s):  
Biosynthetic Pathway ◽  
Early Stage ◽  
Dependent Manner ◽  
Adrenocortical Cell ◽  
Concomitant Increase ◽  
Adrenocortical Cells ◽  
Corticosterone Response ◽  
Dose Dependent ◽  
Predominant Product

Abstract. The effect of Su-10'603 on the cortisol and corticosterone response to histamine in dispersed canine adrenocortical cells was examined. The production of cortisol and corticosterone in isolated dog adrenocortical cell incubations increased in a dose-dependent manner at concentrations of histamine between 0.01 and 10.0 μg/ml medium, with the predominant production of cortisol. When Su-10'603 (0.005 to 5.0 μg/ml medium), an inhibitor of 17α-hydroxylation on corticosteroidogenesis, was added in cell incubations with histamine (1.0 μg/ml medium), the production of cortisol decreased in a reciprocal fashion, with a concomitant increase of corticosterone production. At the concentration between 0.05 and 0.1 μg Su-10'603/ml medium, there was a shift from cortisol to corticosterone as the predominant product. These results indicate that in the dog, histamine at pathophysiological concentration stimulates steroidogenesis and acts at a relatively early stage in the biosynthetic pathway.

scholarly journals Toxicity of chlordane at early developmental stage of zebrafish

2017 ◽  
Author(s):  
Jingxuan Xiong
Keyword(s):  
Early Stage ◽  
Real Life ◽  
Potential Effect ◽  
Early Developmental Stage ◽  
Dependent Manner ◽  
Lower Survival Rate ◽  
Zebrafish Larvae ◽  
Hatching Time ◽  
Early Developmental ◽  
Dose Dependent

AbstractChlordane is highly toxic organochlorine pesticides that have been widely used throughout the world for decades and posing adverse effects on the environment. Contents detected in tissue and blood samples have resulted in a raising concern for their potential effects on wildlife and humans. In this study, we investigate the potential effect of chlordane on the development of zebrafish embryos. Zebrafish larvae were treated with different concentrations (0, 25, 50, 100, 200 ng/L) of chlordane from 12 hours postfertilization (hpf). Different early stage parameters were observed at 1, 2, 3 and 4 day post-fertilization (dpf). Chlordane-exposed zebrafish larvae appeared significant lower survival rate, developmental and hatching time delay and decreased embryo productivity. The heartbeat rate and blood flow were decreased in a dose dependent manner. These results suggested that exposure to real life of chlordane led to direct morphological and phenotypic changes and effects systems related to development and reproduction even in short-term manner.

Oral Supplementation with Omega3 Fatty Acids Inhibits NFkB Activation In Chronic Lymphocytic Leukemia (CLL) Cells.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4607-4607
Author(s):  
Oscar F. F Ballester ◽  
Johannes Fahrmann ◽  
Theodore Witte ◽  
Gabriela Ballester ◽  
W. Elaine Hardman
Keyword(s):  
Conflicts Of Interest ◽  
Early Stage ◽  
Gradient Centrifugation ◽  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
Dependent Manner ◽  
Red Cell ◽  
Omega 3 ◽  
Dose Dependent

Abstract Abstract 4607 Introduction: Nuclear factor kappa B (NFkB) is a critical transcription factor involved in the growth and survival of CLL cells. NFkB is recognized as an important target for the development of novel therapies for the treatment of various malignancies. In vitro and in experimental animal models, OMEGA-3 fatty acid (O3FA) supplementation has been shown to inhibit NFkB activity. Patients and Methods: Patients with early stage CLL (Rai stages 0-II) who required no therapy, where accrued to this phase I-II trial. O3FA supplements were given for a total of 12 months at doses ranging from 2250 mg (EPA plus DHA), escalated to 4500 mg and 6750 mg per day as tolerated. NFkB activity was measured in peripheral blood samples after separation of mononuclear cell by gradient centrifugation and expressed as luminescence units/μ g of protein. Baseline and multiple serial samples were obtained during the study period. In-vitro cytotoxicity assays to doxorubicin were conducted using standard LD50 methods. Compliance was monitored by analysis of red cell and lymphocyte membrane lipid composition by gas chromatography. Results: Fifteen patients have been accrued to the trial, 8 of them have currently completed the planned 12 months of the study period. No significant clinical changes in disease activity were noted. O3FA was well tolerated. Supplementation resulted in a dose-dependent increase of O3FA composition of red cell and lymphocyte membranes in a dose dependent manner. At baseline, CLL patients had NFkB above the range observed in normal controls (2.05 × 104 to 2.32 × 105 NFkB lum units/μ g). The median value in CLL patients at baseline was 11.60 × 106 NFkB lum units/μ g (range 0.9 × 105 to 23.12 × 106). Among 5 patients with the highest baseline levels of NFkB, a decrease in NFkB activity ranging from 0.02 to 0.19 of the baseline value, was noted at the 2 higher doses of O3FA supplementation. Similar results were seen in patients with relatively lower levels of baseline NFkB activity (0.9 × 105 to 2.96 × 106 lum units/μ g). In vitro, significant doxorubicin cytotoxicity (>50%) was noted in samples obtained during supplementation, at μ gM concentrations which produced no detectable cell kill in baseline samples. Conclusions: O3FA supplementation resulted in significant inhibition of NFkB activity in leukemic cells from patients with CLL. In-vitro, after O3FA supplementation CLL cells became more sensitive to doxorubicin. Preliminary analysis of whole genome micro arrays revealed significant down-regulation of multiple genes associated with O3FA supplementation. Disclosures: No relevant conflicts of interest to declare.

scholarly journals In-Vivo Toxicity Studies and In-Vitro Inactivation of SARS-CoV-2 by Povidone-iodine In-situ Gel Forming Formulations

2020 ◽  
Author(s):  
Bo Liang ◽  
Xudong Yuan ◽  
Gang Wei ◽  
Wei Wang ◽  
Ming Zhang ◽  
...  
Keyword(s):  
Povidone Iodine ◽  
Early Stage ◽  
Etiologic Agent ◽  
Dependent Manner ◽  
Forming Technology ◽  
Long Acting ◽  
Dose Dependent

AbstractTo curb the spread of SARS-CoV-2, the etiologic agent of the COVID-19 pandemic, we characterize the virucidal activity of long-acting Povidone Iodine (PVP-I) compositions developed using an in-situ gel forming technology. The PVP-I gel forming nasal spray (IVIEW-1503) and PVP-I gel forming ophthalmic eye drop (IVIEW-1201) rapidly inactivated SARS-CoV-2, inhibiting the viral infection of VERO76 cells. No toxicity was observed for the PVP-I formulations. Significant inactivation was noted with preincubation of the virus with these PVP-I formulations at the lowest concentrations tested. It has been demonstrated that both PVP-I formulations can inactivate SARS-CoV-2 virus efficiently in both a dose-dependent and a time-dependent manner. These results suggest IVIEW-1503 and IVIEW-1201 could be potential agents to reduce or prevent the transmission of the virus through the nasal cavity and the eye, respectively. Further studies are needed to clinically evaluate these formulations in early-stage COVID-19 patients.

scholarly journals The PI3K/Akt pathway is involved in early infection of some exogenous avian leukosis viruses

2011 ◽  
Vol 92 (7) ◽  
pp. 1688-1697 ◽  
Author(s):  
Shao-zhen Feng ◽  
Wei-sheng Cao ◽  
Ming Liao
Keyword(s):  
Viral Entry ◽  
Early Stage ◽  
Dependent Manner ◽  
Phosphatidylinositol 3 Kinase ◽  
Akt Phosphorylation ◽  
Akt Activation ◽  
Pi3k Inhibitors ◽  
Cellular Factors ◽  
Dose Dependent

Avian leukosis virus (ALV) is an enveloped and oncogenic retrovirus. Avian leukosis caused by the members of ALV subgroups A, B and J has become one of the major problems challenging the poultry industry in China. However, the cellular factors such as signal transduction pathways involved in ALV infection are not well defined. In this study, our data demonstrated that ALV-J strain NX0101 infection in primary chicken embryo fibroblasts or DF-1 cells was correlated with the activity and phosphorylation of Akt. Akt activation was initiated at a very early stage of infection independently of NX0101 replication. The specific phosphatidylinositol 3-kinase (PI3K) inhibitors LY294002 or wortmannin could suppress Akt phosphorylation, indicating that NX0101-induced Akt phosphorylation is PI3K-dependent. ALV-A strain GD08 or ALV-B strain CD08 infection also demonstrated a similar profile of PI3K/Akt activation. Treatment of DF-1 cells with the drug 5-(N, N-hexamethylene) amiloride that inhibits the activity of chicken Na+/H+ exchanger type 1 significantly reduced Akt activation induced by NX0101, but not by GD08 and CD08. Akt activation triggered by GD08 or CD08 was abolished by clathrin-mediated endocytosis inhibitor chlorpromazine. Receptor-mediated endocytosis inhibitor dansylcadaverine had a negligible effect on all ALV-induced Akt phosphorylation. Moreover, viral replication of ALV was suppressed by LY294002 in a dose-dependent manner, which was due to the inhibition of virus infection by LY294002. These data suggest that the activation of the PI3K/Akt signalling pathway by exogenous ALV infection plays an important role in viral entry, yet the precise mechanism remains under further investigation.

Inhibitory effects of gossypol on adrenal function

1991 ◽  
Vol 124 (6) ◽  
pp. 672-678 ◽  
Author(s):  
Yan-Wan Wu ◽  
Constance L. Chik ◽  
Barry D. Albertson ◽  
W. Marston Linehan ◽  
Richard A. Knazek
Keyword(s):  
Adrenal Function ◽  
Dependent Manner ◽  
Inhibitory Effects ◽  
Acth Stimulation ◽  
Adrenal Steroidogenesis ◽  
Cortisol Responses ◽  
Corticosterone Response ◽  
High Doses ◽  
Dose Dependent

Abstract. Gossypol, an antifertility agent, has inhibitory actions on many membrane-associated enzymes, suggesting that this agent might have a generalized effect on cell membranes. This hypothesis was examined in the present study using membranes and dispersed cells prepared from human and rat adrenal glands. Four parameters were determined: microviscosity as measured by fluorescence polarization of human adrenal microsomal- and mitochondrial-enriched membranes, adrenal steroidogenic enzymes; and cAMP and cortisol responses to ACTH. It was found that gossypol increased the polarization constants of microsomes and mitochondria in a dose-dependent manner. Of the three adrenal enzymes tested, both 3β-hydroxysteroid dehydrogenase Δ5-Δ4 isomerase and 11-hydroxylase were inhibited by gossypol, but not 21-hydroxylase. Using intact human adrenocortical cells, high doses of gossypol also inhibited the ACTH-stimulated cAMP and cortisol levels. The in vivo corticosterone response to ACTH in rats subjected to chronic gossypol treatment was also found to be reduced. These findings suggest that gossypol has multiple effects on adrenal function. Its effects on membrane microviscosity, adrenal steroidogenesis, cAMP and corticosterone responses to ACTH stimulation probably occur through a generalized membrane effect.

Circulatory GSK-3β: Blood-Based Biomarker and Therapeutic Target for Alzheimer’s Disease

2021 ◽  
pp. 1-12
Author(s):  
Shiwani Kumari ◽  
Ambica Singh ◽  
Abhinay Kumar Singh ◽  
Yudhishthir Yadav ◽  
Swati Bajpai ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Stage ◽  
Memory Loss ◽  
Amyloid Β ◽  
Clear Understanding ◽  
Dependent Manner ◽  
Brain Disorder ◽  
Gsk 3Β ◽  
Dose Dependent

Background: Alzheimer’s disease (AD) is the progressive brain disorder which degenerates brain cells connection and causes memory loss. Although AD is irreversible, it is not impossible to arrest or slow down the progression of the disease. However, this would only be possible if the disease is diagnosed at an early stage, and early diagnosis requires clear understanding of the pathogenesis at molecular level. Overactivity of GSK-3β and p53 accounts for tau hyperphosphorylation and the formation of amyloid-β plaques. Objective: Here, we explored GSK-3β and p53 as blood-based biomarkers for early detection of AD. Methods: The levels of GSK-3β, p53, and their phosphorylated states were measured using surface plasmon resonance and verified using western blot in serum from AD, mild cognitive impairment (MCI), and geriatric-control (GC) subjects. The neurotoxic SH-SY5Y cell line was treated with antioxidant Emblica Officinalis (EO) for rescue effect. Results: GSK-3β, p53, and their phosphorylated states were significantly over expressed (p >  0.001) in AD and MCI compared to GC and can differentiate AD and MCI from GC. The expression level of GSK-3β and p53 proteins were found to be downregulated in a dose-dependent manner after the treatment with EO in amyloid-b-induced neurotoxic cells. Conclusion: These proteins can serve as potential blood markers for the diagnosis of AD and EO can suppress their level. This work has translational value and clinical utility in the future.

Glucocorticoids enhance corticotropin receptor mRNA levels in ovine adrenocortical cells

1997 ◽  
Vol 19 (1) ◽  
pp. 29-36 ◽  
Author(s):  
N Picard-Hagen ◽  
A Penhoat ◽  
D Hue ◽  
C Jaillard ◽  
P Durand
Keyword(s):  
Cultured Cells ◽  
Concomitant Treatment ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Dexamethasone Treatment ◽  
Adrenocortical Cells ◽  
Trophic Effect ◽  
Receptor Mrna ◽  
Acth Receptor ◽  
Dose Dependent

ABSTRACT We have shown previously that chronic treatment with glucocorticoids enhances both ACTH-induced cAMP production and ACTH- or 8Br-cAMP-induced steroidogenesis of cultured ovine adrenocortical cells. This treatment has been shown to involve an increase in the number of ACTH receptors. The present study aimed to explore the mechanism of this effect of glucocorticoids on ACTH receptors. Ovine adrenocortical cells expressed one major ACTH receptor transcript of 3·6 kb and three minor ones of 4·2, 1·8 and 1·3 kb. Dexamethasone treatment of cultured cells increased the levels of all these transcripts in a time- and dose-dependent manner, with an EC50 of (1·5±0·6) × 10−8 m. The mean increase over control with 10−6 m dexamethasone was 144 ± 11% (n=14). This enhancing effect was specific for glucocorticosteroids. The antiglucocorticoid Ru38486 blocked the effect of dexamethasone. Testosterone did not modify, while high concentrations of 17β-estradiol decreased, ACTH receptor mRNA levels. Treatment of cells with aminoglutethimide (an inhibitor of steroidogenesis) resulted in a dose-dependent decrease in ACTH receptor mRNA levels, which was prevented by concomitant treatment with dexamethasone. Treatment with ACTH also increased ACTH receptor mRNA levels more than twofold. Addition of aminoglutethimide together with ACTH resulted in a smaller increase than that achieved with ACTH alone. Neither dexamethasone nor ACTH modified ACTH receptor mRNA half-lives. However, these two hormones enhanced the levels of both newly synthesized and total ACTH receptor mRNAs. These results indicate that the positive trophic effect of glucocorticoids on ovine adrenocortical cells involves an enhancement of the transcription rate of the ACTH receptor gene. In addition, they suggest that part of the trophic action of ACTH on ACTH receptors may be mediated by ACTH-induced steroidogenesis.

scholarly journals An Oleanolic Acid Derivative Inhibits Hemagglutinin-Mediated Entry of Influenza A Virus

Viruses ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 225 ◽  
Author(s):  
Mengdie Ye ◽  
Yixian Liao ◽  
Li Wu ◽  
Wenbao Qi ◽  
Namrta Choudhry ◽  
...  
Keyword(s):  
Membrane Fusion ◽  
Conformational Changes ◽  
Influenza A ◽  
Dissociation Constants ◽  
Early Stage ◽  
Dependent Manner ◽  
Influenza A Viruses ◽  
Endosomal Membrane ◽  
Chicken Erythrocytes ◽  
Dose Dependent

Influenza A viruses (IAV) have been a major public health threat worldwide, and options for antiviral therapy become increasingly limited with the emergence of drug-resisting virus strains. New and effective anti-IAV drugs, especially for highly pathogenic influenza, with different modes of action, are urgently needed. The influenza virus glycoprotein hemagglutinin (HA) plays critical roles in the early stage of virus infection, including receptor binding and membrane fusion, making it a potential target for the development of anti-influenza drugs. In this study, we show that OA-10, a newly synthesized triterpene out of 11 oleanane-type derivatives, exhibited significant antiviral activity against four different subtypes of IAV (H1N1, H5N1, H9N2 and H3N2) replications in A549 cell cultures with EC50 ranging from 6.7 to 19.6 μM and a negligible cytotoxicity (CC50 > 640 μM). It inhibited acid-induced hemolysis in a dose-dependent manner, with an IC50 of 26 µM, and had a weak inhibition on the adsorption of H5 HA to chicken erythrocytes at higher concentrations (≥40 µM). Surface plasmon resonance (SPR) analysis showed that OA-10 interacted with HA in a dose-dependent manner with the equilibrium dissociation constants (KD) of the interaction of 2.98 × 10−12 M. Computer-aided molecular docking analysis suggested that OA-10 might bind to the cavity in HA stem region which is known to undergo significant rearrangement during membrane fusion. Our results demonstrate that OA-10 inhibits H5N1 IAV replication mainly by blocking the conformational changes of HA2 subunit required for virus fusion with endosomal membrane. These findings suggest that OA-10 could serve as a lead for further development of novel virus entry inhibitors to prevent and treat IAV infections.

Human Recombinant Activin-A Modulates the Steroidogenesis of Cultured Bovine Adrenocortical Cells

1992 ◽  
Vol 132 (3) ◽  
pp. R1-R4 ◽  
Author(s):  
Y. Nishi ◽  
M. Haji ◽  
S. Tanaka ◽  
T. Yanase ◽  
R. Takayanagi ◽  
...  
Keyword(s):  
Inhibitory Effect ◽  
Activin A ◽  
Dependent Manner ◽  
Cortisol Secretion ◽  
Inhibitory Effects ◽  
Aldosterone Secretion ◽  
Adrenocortical Cells ◽  
Adrenal Steroidogenesis ◽  
Direct Inhibitory Effect ◽  
Dose Dependent

ABSTRACT The effect of human recombinant activin-A on adrenal steroidogenesis was studied in cultured bovine adrenocortical cells. Activin-A significantly reduced cortisol output from ACTH (10nmol/l)-stimulated adrenocortical cells incubated for 24 hours in a dose-dependent manner (10, 100 and 500ng activin-A /ml suppressed cortisol secretion by 19, 33 and 40%), although no significant effect was observed in the case of 3 h incubation. Dehydroepiandrosterone (DHEA) secretion from ACTH-stimulated adrenocortical cells incubated for 24 h was also decreased by the addition of activin-A in a dose-dependent manner. (10, 100 and 500ng activin-A /ml suppressed DHEA secretion by 22, 56 and 58%). These inhibitory effects of activin-A (100ng/ml) on cortisol and DHEA secretion were partially blocked by the addition of follistatin / FSH-Suppressing Protein (200ng/ml). In contrast, activin-A treatment resulted in no significant decrease in aldosterone secretion. There were no significant effects of activin-A on basal secretions of cortisol, DHEA or aldosterone from adrenocortical cells. These results suggest that activin-A has a direct inhibitory effect on ACTH-stimulated bovine adrenocortical steroidogenesis.

Whole-cell recording of light-evoked photoreceptor responses in a slice preparation of the cuttlefish retina

2005 ◽  
Vol 22 (3) ◽  
pp. 359-370 ◽  
Author(s):  
ABDESSLAM CHRACHRI ◽  
LISA NELSON ◽  
RODDY WILLIAMSON
Keyword(s):  
Time Course ◽  
Early Stage ◽  
Outward Current ◽  
Delayed Rectifier ◽  
Dependent Manner ◽  
Slice Preparation ◽  
Whole Cell ◽  
Inward Current ◽  
Transient Inward Current ◽  
Dose Dependent

A new tissue slice preparation of the cuttlefish eye is described that permits patch-clamp recordings to be acquired from intact photoreceptors during stimulation of the retina with controlled light flashes. Whole-cell recordings using this preparation, from the retinas of very youngSepia officinalisdemonstrated that the magnitude, latency, and kinetics of the flash-induced photocurrent are closely dependent on the magnitude of the flash intensity. Depolarizing steps to voltages more positive than −40 mV, from a membrane holding potential of −60 mV, induced a transient inward current followed by a larger, more sustained outward current in these early-stage photoreceptors. The latter current resembled the delayed rectifier (IK) already identified in many other nerve cells, including photoreceptors. This current was activated at −30 mV from a holding potential of −60 mV, had a sustained time course, and was blocked in a dose-dependent manner by tetraethylammonium chloride (TEA). The smaller, transient, inward current appeared at potentials more positive than −50 mV, reached peak amplitude at −30 mV and decreased with further depolarization. This current was characterized as the sodium current (INa) on the basis that it was inactivated at holding potentials above −40 mV, was blocked by tetrodotoxin (TTX) and was insensitive to cobalt.Intracellular perfusion of the photoreceptors,viathe patch pipette, demonstrated that U-73122 and heparin blocked the evoked photocurrent in a dose-dependent manner, suggesting the involvement of the phospholipase C (PLC) and inositol 1,4,5-triphosphate (InsP3), respectively, in the phototransduction cascade. Perfusion with cyclic GMP increased significantly the evoked photocurrent, while the inclusion of phorbol-12,13-dibutyrate reduced significantly the evoked photocurrent, supporting the involvement of cGMP and the diacylglycerol (DAG) pathways, respectively, in the cuttlefish transduction process.

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