Effects of in vivo triiodothyronine and long acting thyroid stimulator (LATS) administration on the in vitro thyroid cAMP response to thyrotrophin and LATS

1984 ◽  
Vol 106 (2) ◽  
pp. 193-198 ◽  
Author(s):  
Hitoshi Ikeda ◽  
Shoo Cheng Chiu ◽  
Nobuaki Kuzuya ◽  
Hidemasa Uchimura ◽  
Shigenobu Nagataki
Keyword(s):  
Drinking Water ◽  
Combined Treatment ◽  
Inhibitory Effects ◽  
Wet Weight ◽  
Per Se ◽  
Thyroid Hormone Levels ◽  
Long Acting ◽  
Mouse Thyroid

Abstract. The present study was undertaken to examine the effects of prolonged in vivo treatment with T3 and long acting thyroid stimulator (LATS) on in vitro responsiveness of mouse thyroid cyclic AMP to thyrotrophin (TSH) and LATS-immunoglobulin G (IgG). In control mice, thyroid cAMP concentrations after incubation with normal-IgG (10 mg/ml) for 2 h. TSH (10 mU/ml) for 10 min and LATS-IgG (10 mg/ml) for 2 h were 1.25 ± 0.11 (mean ± se) (n = 5), 15.87 ± 3.47 (n = 6) and 2.17 ± 0.25 pmoles/mg wet weight (n = 6), respectively. In mice given T3 (5 μg/ml in drinking water for 5 days, thyroid cAMP concentrations after an incubation with TSH were reduced by 50%, as compared to those of the control mice. They were also decreased in mice injected ip with 5 mg of LATS-IgG (1000%/5 mg in the McKenzie bioassay) daily for 5 days. Combined treatment with T3 and LATS decreased the cAMP response to TSH only to the same extent as did T3 alone, indicating that the inhibitory effects of T3 and LATS were not additive. Similar findings were observed with the thyroid cAMP response to LATS-IgG in vitro; either T3 or LATS treatment in vivo decreased cAMP response to LATS-IgG in vitro, but combined treatment with T3 and LATS did not cause further inhibition as compared with T3 or LATS treatment alone. These results indicate, 1) that prolonged in vivo T3 treatment inhibits the in vitro thyroid cAMP response not only to TSH but also to LATS-IgG, 2) that prolonged in vivo LATS treatment also suppresses the thyroid cAMP response both to TSH and LATS-IgG and 3) that the inhibitory effects of LATS may not be due to the effects of LATS per se but to increases in circulating thyroid hormone levels induced by prolonged LATS treatment.

Tonic effect of endogenous TSH on the in vitro thyroid cAMP response to TSH

1984 ◽  
Vol 107 (4) ◽  
pp. 489-494 ◽  
Author(s):  
Hitoshi Ikeda ◽  
Hidemasa Uchimura ◽  
Shigenobu Nagataki
Keyword(s):  
Drinking Water ◽  
Combined Treatment ◽  
Concomitant Treatment ◽  
Camp Production ◽  
Trophic Effect ◽  
The Third ◽  
Mouse Thyroid

Abstract. The present study was undertaken to compare the effects of 3,5,3'-triiodothyronine (T3) alone and T3 plus bovine thyrotrophin (bTSH) given chronically in vivo on the TSH-stimulated cyclic adenosine 3',5'-monophosphate (cAMP) production in a mouse thyroid in vitro. Mice were given T3 (5 μg/ml) in drinking water for 4 days. The thyroid cAMP concentrations after an incubation with 10 mU/ml of TSH for 10 min were decreased by 50% in T3-treated mice as compared to the control. In the second experiment, mice were given T3 alone or T3 plus 0.5 mU of bTSH ip daily for 4 days. The combined treatment with T3 and TSH partially restored the reduction of cAMP response to TSH that was induced by T3 alone. In the third experiment, mice were given T3 alone for 7 days, or T3 for 7 days plus TSH for the last 3 days. The reduced cAMP response to TSH induced by T3 alone was again partially restored by the concomitant treatment with TSH. These results indicate 1) that the capacity of the thyroid cAMP to respond to TSH is regulated, at least in part, by a trophic effect of endogenous TSH and 2) that the impaired capacity caused by a loss of tonic effect of endogenous TSH is reversible.

A NEW IN VITRO ASSAY FOR THYROIDSTIMULATING HORMONE

1967 ◽  
Vol 38 (4) ◽  
pp. 439-449 ◽  
Author(s):  
JILL BROWN ◽  
D. S. MUNRO
Keyword(s):  
Radioactive Iodine ◽  
Thyroid Stimulating Hormone ◽  
Vitro Assay ◽  
Line Parallel ◽  
Thyroid Glands ◽  
Long Acting ◽  
Response Line ◽  
Mouse Thyroid

SUMMARY A new in vitro assay for thyroid-stimulating hormone (TSH) is described. The parameter of TSH action is the discharge of radioactive iodine from mouse thyroid glands labelled with 131I in vivo. The assay is sensitive to human TSH and gave consistent results during 1 yr. without seasonal variation. A potent preparation of long-acting thyroid stimulator gave a dose-response line parallel with human TSH. Fresh human serum was toxic to the assay preparation so that circulating TSH levels cannot be measured.

Ex vivo/In vitro Interaction between ASA, Clopidogrel and GPIIb/IIIa-Inhibitors

1999 ◽  
Vol 19 (03) ◽  
pp. 112-114
Author(s):  
C. M. Kirchmaier ◽  
Dagmar Westrup ◽  
J. Graff ◽  
R. Mahnel ◽  
H. K. Breddin ◽  
...  
Keyword(s):  
Combined Treatment ◽  
Healthy Male ◽  
Inhibitory Effects ◽  
Healthy Male Volunteers ◽  
Male Volunteers ◽  
Fibrinogen Binding ◽  
In Vitro Interaction ◽  
Induced Aggregation

SummaryWe report on an in vivo interaction study between aspirin (ASA) and Clopidogrel in healthy male volunteers and on an in-vitro interaction of abciximab and the peptidomimetic GPIIb/IIIa-inhibitor SR121566A with blood from subjects of the in vivo-study. Ten healthy male volunteers were randomly assigned to two groups (N = 5). Group 1 started with ASA and group 2 with Clopidogrel. From day 4 to 8 subjects of both groups received combined treatment with ASA and Clopidogrel. Blood from volunteers was spiked with abciximab or SR121566A. Inhibitory effects of ASA and Clopidogrel on collagen- or ADP-induced platelet aggregation were not enhanced by the combination of both drugs. TRAP-induced fibrinogen binding was reduced under ASA to 69% (n.s.), and to 63% under Clopidogrel or Clopidogrel + ASA. CD62-expression was reduced to 66% by Clopidogrel (p <0.01 ), whereas ASA had no effect. A further significant reduction to 41 % (difference to clopidogrel/ASA alone p <0.01), was seen under combined treatment (day 8). ASA and Clopidogrel increased the effects of the GPIIb/IIIa-inhibitors on collagen (2 pg/ml)- and ADP (5 pM)-induced aggregation. Under treatment with ASA and Clopidogrel inhibitory effects of GPIIb/IIIa-inhibitors on fibrinogen binding were additive to changes seen with ASA/clopidogrel alone. No additional effect on CD62 was seen with either GPIIb/IIIa-inhibitor.

Inhibitory effects of epimedium herb water extract on the inflammatory response in vitro and in vivo

Planta Medica ◽  
2016 ◽  
Vol 81 (S 01) ◽  
pp. S1-S381
Author(s):  
YC Oh ◽  
YH Jeong ◽  
WK Cho ◽  
SJ Lee ◽  
JY Ma
Keyword(s):  
Inflammatory Response ◽  
Water Extract ◽  
Inhibitory Effects

The Effects of Brinolase (Fibrinolytic Enzyme from Aspergillus Oryzae) on Platelet Aggregation of Dog and Man

1972 ◽  
Vol 28 (01) ◽  
pp. 031-048 ◽  
Author(s):  
W. H. E Roschlau ◽  
R Gage
Keyword(s):  
Platelet Aggregation ◽  
Aspergillus Oryzae ◽  
Degradation Products ◽  
Blood Platelet ◽  
Human Platelets ◽  
Fibrinolytic Enzyme ◽  
Inhibitory Effects ◽  
Blood Platelet Aggregation

SummaryInhibition of blood platelet aggregation by brinolase (fibrinolytic enzyme from Aspergillus oryzae) has been demonstrated with human platelets in vitro and with dog platelets in vivo and in vitro, using both ADP and collagen as aggregating stimuli. It is suggested that the optimal inhibitory effects of brinolase occur indirectly through the generation of plasma fibrinogen degradation products, without compromising platelet viability, rather than by direct proteolysis of platelet structures.

THYROID STIMULATORS AND THYROID STIMULATION

1971 ◽  
Vol 66 (3) ◽  
pp. 558-576 ◽  
Author(s):  
Gerald Burke
Keyword(s):  
Regulatory System ◽  
Control Site ◽  
Thyroid Cell ◽  
Primary Control ◽  
Physico Chemical ◽  
Site Of Action ◽  
Long Acting

ABSTRACT A long-acting thyroid stimulator (LATS), distinct from pituitary thyrotrophin (TSH), is found in the serum of some patients with Graves' disease. Despite the marked physico-chemical and immunologic differences between the two stimulators, both in vivo and in vitro studies indicate that LATS and TSH act on the same thyroidal site(s) and that such stimulation does not require penetration of the thyroid cell. Although resorption of colloid and secretion of thyroid hormone are early responses to both TSH and LATS, available evidence reveals no basic metabolic pathway which must be activated by these hormones in order for iodination reactions to occur. Cyclic 3′, 5′-AMP appears to mediate TSH and LATS effects on iodination reactions but the role of this compound in activating thyroidal intermediary metabolism is less clear. Based on the evidence reviewed herein, it is suggested that the primary site of action of thyroid stimulators is at the cell membrane and that beyond the(se) primary control site(s), there exists a multifaceted regulatory system for thyroid hormonogenesis and cell growth.

scholarly journals Inhibitory Effects of a Reengineered Anthrax Toxin on Canine Oral Mucosal Melanomas

Toxins ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 157 ◽  
Author(s):  
Adriana Tomoko Nishiya ◽  
Marcia Kazumi Nagamine ◽  
Ivone Izabel Mackowiak da Fonseca ◽  
Andrea Caringi Miraldo ◽  
Nayra Villar Scattone ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Evaluation Criteria ◽  
Anthrax Toxin ◽  
Treatment Modalities ◽  
Inhibitory Effects ◽  
Upa Receptor ◽  
New Treatment ◽  
Oral Malignancy

Canine oral mucosal melanomas (OMM) are the most common oral malignancy in dogs and few treatments are available. Thus, new treatment modalities are needed for this disease. Bacillus anthracis (anthrax) toxin has been reengineered to target tumor cells that express urokinase plasminogen activator (uPA) and metalloproteinases (MMP-2), and has shown antineoplastic effects both, in vitro and in vivo. This study aimed to evaluate the effects of a reengineered anthrax toxin on canine OMM. Five dogs bearing OMM without lung metastasis were included in the clinical study. Tumor tissue was analyzed by immunohistochemistry for expression of uPA, uPA receptor, MMP-2, MT1-MMP and TIMP-2. Animals received either three or six intratumoral injections of the reengineered anthrax toxin prior to surgical tumor excision. OMM samples from the five dogs were positive for all antibodies. After intratumoral treatment, all dogs showed stable disease according to the canine Response Evaluation Criteria in Solid Tumors (cRECIST), and tumors had decreased bleeding. Histopathology has shown necrosis of tumor cells and blood vessel walls after treatment. No significant systemic side effects were noted. In conclusion, the reengineered anthrax toxin exerted inhibitory effects when administered intratumorally, and systemic administration of this toxin is a promising therapy for canine OMM.

scholarly journals Long-Acting Risperidone Dual Control System: Preparation, Characterization and Evaluation In Vitro and In Vivo

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1210
Author(s):  
Xieguo Yan ◽  
Shiqiang Wang ◽  
Kaoxiang Sun
Keyword(s):  
Drug Loading ◽  
Entrapment Efficiency ◽  
In Vitro Dissolution ◽  
Dissolution Behavior ◽  
In Vivo Evaluation ◽  
Long Term Treatment ◽  
Long Acting

Schizophrenia, a psychiatric disorder, requires long-term treatment; however, large fluctuations in blood drug concentration increase the risk of adverse reactions. We prepared a long-term risperidone (RIS) implantation system that can stabilize RIS release and established in-vitro and in-vivo evaluation systems. Cumulative release, drug loading, and entrapment efficiency were used as evaluation indicators to evaluate the effects of different pore formers, polymer ratios, porogen concentrations, and oil–water ratios on a RIS implant (RIS-IM). We also built a mathematical model to identify the optimized formulation by stepwise regression. We also assessed the crystalline changes, residual solvents, solubility and stability after sterilization, in-vivo polymer degradation, pharmacokinetics, and tissue inflammation in the case of the optimized formulation. The surface of the optimized RIS microspheres was small and hollow with 134.4 ± 3.5 µm particle size, 1.60 SPAN, 46.7% ± 2.3% implant drug loading, and 93.4% entrapment efficiency. The in-vitro dissolution behavior of RIS-IM had zero-order kinetics and stable blood concentration; no lag time was released for over three months. Furthermore, the RIS-IM was not only non-irritating to tissues but also had good biocompatibility and product stability. Long-acting RIS-IMs with microspheres and film coatings can provide a new avenue for treating schizophrenia.

scholarly journals Development of In Situ Self-Assembly Nanoparticles to Encapsulate Lopinavir and Ritonavir for Long-Acting Subcutaneous Injection

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 904
Author(s):  
Irin Tanaudommongkon ◽  
Asama Tanaudommongkon ◽  
Xiaowei Dong
Keyword(s):  
Sustained Release ◽  
Trough Concentration ◽  
Self Assembly ◽  
Subcutaneous Injection ◽  
Drug Loading ◽  
Entrapment Efficiency ◽  
Long Acting

Most antiretroviral medications for human immunodeficiency virus treatment and prevention require high levels of patient adherence, such that medications need to be administered daily without missing doses. Here, a long-acting subcutaneous injection of lopinavir (LPV) in combination with ritonavir (RTV) using in situ self-assembly nanoparticles (ISNPs) was developed to potentially overcome adherence barriers. The ISNP approach can improve the pharmacokinetic profiles of the drugs. The ISNPs were characterized in terms of particle size, drug entrapment efficiency, drug loading, in vitro release study, and in vivo pharmacokinetic study. LPV/RTV ISNPs were 167.8 nm in size, with a polydispersity index of less than 0.35. The entrapment efficiency was over 98% for both LPV and RTV, with drug loadings of 25% LPV and 6.3% RTV. A slow release rate of LPV was observed at about 20% on day 5, followed by a sustained release beyond 14 days. RTV released faster than LPV in the first 5 days and slower than LPV thereafter. LPV trough concentration remained above 160 ng/mL and RTV trough concentration was above 50 ng/mL after 6 days with one subcutaneous injection. Overall, the ISNP-based LPV/RTV injection showed sustained release profiles in both in vitro and in vivo studies.

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