Seizures in Rats Associated with Divalent Cation Inhibition of Na+–K+-ATP'ase

1971 ◽  
Vol 49 (11) ◽  
pp. 1217-1224 ◽  
Author(s):  
J. Donaldson ◽  
T. St-Pierre ◽  
J. Minnich ◽  
A. Barbeau
Keyword(s):  
Divalent Cation ◽  
Regional Analysis ◽  
Intraventricular Injection ◽  
Specific Inhibition ◽  
Low Doses ◽  
High Doses ◽  
Very High

In vitro determination of rat brain microsomal ATP'ase activity revealed specific inhibition of the Na+–K+-ATP'ase by cations in the order Zn2+ > Cu2+ > Fe2+ > Mn2+. Intraventricular injection of the same cations or of ouabain resulted in convulsions. Regional analysis of ATP'ase from brains of rats after convulsions showed inhibited Na+–K+-ATP'ase activity in hippocampus and hypothalamus. Hippocampus and hypothalamus were found to have the highest Na+–K+-ATP'ase activity in the rat brain.The potent inhibitors of Na+–K+-ATP'ase in vitro (ouabain, Zn2+, and Cu2+) were similarly effective in vivo (hippocampus and hypothalamus), while the inhibitors relatively ineffective in vitro (Fe2+ and Mn2+) were similarly of low potency in vivo. The potent inhibitors of Na+–K+-ATP'ase caused convulsions at low doses; the ineffective inhibitors caused convulsions only at very high doses.

Inhibition of testosterone metabolism in the brain and cloacal gland of the quail by specific inhibitors and antihormones

1987 ◽  
Vol 112 (2) ◽  
pp. 189-195 ◽  
Author(s):  
C. Alexandre ◽  
J. Balthazart
Keyword(s):  
Reductase Inhibitor ◽  
Aromatase Activity ◽  
Testosterone Metabolism ◽  
In Vivo Experiments ◽  
High Doses ◽  
The Brain ◽  
Very High ◽  
Cloacal Gland

ABSTRACT The effects of antioestrogens, antiandrogens and of various inhibitors of testosterone metabolism on testosterone metabolism in the quail hypothalamus and cloacal gland were studied by an in-vitro radio-enzymatic assay. It was found that antioestrogens and antiandrogens generally had little or no effect on aromatase and 5α- and 5β-reductases of testosterone, except when used at very high doses. The 5α-reductase inhibitor, 17β-N,N-diethylcarbamoyl-4-methyl-4-aza-5α-androstan-3-one, inhibited both 5α- and 5β-dihydrotestosterone production without markedly affecting aromatase activity. Surprisingly, the aromatase inhibitor, 1,4,6-androstatriene-3,17-dione, inhibited not only the production of oestradiol but also that of 5β-dihydrotestosterone and, to a lesser extent, 5α-dihydrotestosterone. These unexpected properties should be taken into account when interpreting the results of in-vivo experiments using these compounds. J. Endocr. (1987) 112, 189–195

THE EFFECT OF EXOGENOUS RIBONUCLEIC ACID ON ALKALINE PHOSPHATASE ACTIVITY IN THE OVARIECTOMIZED MOUSE UTERUS

1968 ◽  
Vol 57 (3) ◽  
pp. 465-472 ◽  
Author(s):  
A. Maher Mansour
Keyword(s):  
Alkaline Phosphatase ◽  
Alkaline Phosphatase Activity ◽  
Ribonucleic Acid ◽  
Mouse Uterus ◽  
Ovariectomized Mice ◽  
Before And After ◽  
High Doses ◽  
Very High

ABSTRACT RNA from tissues subjected to very high doses of 17β-oestradiol in vivo and in vitro was injected into the uteri of ovariectomized mice before and after ether washing of the RNA. Alkaline phosphatase content of the atrophied uterus was measured after the RNA injections. Results indicate that alkaline phosphatase induction is due to RNA and that ether washing completely eliminates hormonal contamination. The role played by the hormone-cytoplasm requires further attention.

CYCLOOXYGENASE INDIPENDENT PLATELET AGGREGATION:RELATION WITH ASPI RIN CONCENTRATION

1987 ◽  
Author(s):  
C Cordova ◽  
F Violi ◽  
D Praticò ◽  
A Ghiselli ◽  
C Alessandri ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Platelet Rich Plasma ◽  
Low Doses ◽  
Dose Dependent Fashion ◽  
Threshold Doses ◽  
High Doses ◽  
Dose Dependent

Low doses of aspirin (20 mg/day) were previously reported to be uneffective in preventing platelet aggregation (PA) induced by pairs of aggregating agents such as PAF and adrenalin.This was in part attributed to the inability of such treatment to inhibit lipo oxygenase-dependent PA.The latter can be observed in vitro in"aspl rinated"platelets stimulated with high quantities of aggregating -agents.The aim of this study was to evaluate if the lipooxygenase-dependent PA was influenced by aspirin in a dose-dependent fashion. PA was studied in platelet rich plasma (PRP)(Born's method) by using threshold doses of aggregating agents (TDA) such as PAF(4-75 nM),epinephrine(0.6-2 μM) and collagen(2-4 μg/ml).PA performed in PRP pretrated with 100μM aspirin was fully prevented;in the same samples thromboxane (Tx) A2 evaluated by its metabolite Tx B2 was almost absent.Increasing amount of PAF(20 fold TDA),epinephrine(20 fold TDA) and collagen (36 fold TDA) do aggregate"aspirinated"pla telets;similarly"aspirinated"platelets aggregate when stimulated-with a pair of aggregating agents (TDA of PAF+epinephrine).This phenomenon was not detected if platelets were incubated with higher amounts of aspirin (250-500 μM).The study suggests that aspirin could influence lipooxygenase-dependent PA.This hypothesis is sup ported by a research showing the aspirin inhibits dose-dependently platelet HETE formation.A further study is now in progress to eva luate the influence of high doses of aspirin on cyclooxygenase-i"n dependent PA in vivo.

Commentary on ‘Resveratrol commonly displays hormesis: Occurrence and biomedical significance’

2010 ◽  
Vol 29 (12) ◽  
pp. 1024-1025 ◽  
Author(s):  
David G Lindsay
Keyword(s):  
Dose Response ◽  
Low Doses ◽  
Response Relationship ◽  
Dose Response Relationship ◽  
Beneficial Effects ◽  
In Vitro Systems ◽  
High Doses

Many phenolics found naturally in food have the capacity to show beneficial effects at low doses and toxicity at high doses in in vitro systems. Resveratrol is no exception. Nonetheless, in the nutritional context, the evidence that resveratrol shows hormetic effects is very limited and is of questionable relevance given its rapid metabolism in the stomach. Hormesis can only be confirmed if evidence for a J- or U-shaped dose-response relationship is found in in vivo doses that are relevant to human intakes.

A Molecular Approach to Immunoscintigraphy: A Study of the T-Antigen Conformation on the Surface of Tumors

1987 ◽  
Vol 26 (01) ◽  
pp. 1-6 ◽  
Author(s):  
S. Selvaraj ◽  
M. R. Suresh ◽  
G. McLean ◽  
D. Willans ◽  
C. Turner ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Tumor Cell ◽  
T Antigen ◽  
Human Carcinomas ◽  
Animal Tumor ◽  
Synthetic Antigens

The role of glycoconjugates in tumor cell differentiation has been well documented. We have examined the expression of the two anomers of the Thomsen-Friedenreich antigen on the surface of human, canine and murine tumor cell membranes both in vitro and in vivo. This has been accomplished through the synthesis of the disaccharide terminal residues in both a and ß configuration. Both entities were used to generate murine monoclonal antibodies which recognized the carbohydrate determinants. The determination of fine specificities of these antibodies was effected by means of cellular uptake, immunohistopathology and immunoscintigraphy. Examination of pathological specimens of human and canine tumor tissue indicated that the expressed antigen was in the β configuration. More than 89% of all human carcinomas tested expressed the antigen in the above anomeric form. The combination of synthetic antigens and monoclonal antibodies raised specifically against them provide us with invaluable tools for the study of tumor marker expression in humans and their respective animal tumor models.

Storage of Human Blood Platelets

1974 ◽  
Vol 32 (02/03) ◽  
pp. 405-416 ◽  
Author(s):  
M. R Hardeman ◽  
Carina J L. Heynens
Keyword(s):  
Storage Temperature ◽  
Platelet Rich Plasma ◽  
Blood Platelets ◽  
Storage Period ◽  
Serotonin Uptake ◽  
Hypotonic Shock ◽  
Glycolytic Intermediates

SummaryStorage experiments were performed at 4°, 25° and 37° C with platelet-rich plasma under sterile conditions. In some experiments also the effect of storing platelets at 4° C in whole blood was investigated.Before, during and after three days of storage, the platelets were tested at 37° C for their serotonin uptake and response to hypotonic shock. In addition some glycolytic intermediates were determined.A fair correlation was noticed between the serotonin uptake and hypotonic shock experiments. Both parameters were best maintained at 25° C. Also platelet counting, performed after the storage period, indicated 25° C as the best storage temperature. Determination of glycolytic intermediates did not justify any conclusion regarding the optimal storage temperature. Of the various anticoagulants studied, ACD and heparin gave the best results as to the serotonin uptake and hypotonic shock response, either with fresh or stored platelets. The use of EDTA resulted in the lowest activity, especially after storage.The results of these storage experiments in vitro, correspond well with those in vivo reported in the literature.

In Vivo Effect of Suloctidil as an Antiplatelet Agent

1979 ◽  
Vol 41 (03) ◽  
pp. 465-474 ◽  
Author(s):  
Marcia R Stelzer ◽  
Thomas S Burns ◽  
Robert N Saunders
Keyword(s):  
Ex Vivo ◽  
Antiplatelet Agent ◽  
Ratio Method ◽  
Platelet Aggregate ◽  
Permanent Effect ◽  
Platelet Aggregates ◽  
5 Ht Uptake ◽  
High Doses

SummaryThe relationship between the effects of suloctidil in vivo as an antiplatelet agent and in vitro as a modifier of platelet serotonin (5-HT) parameters was investigated. Suloctidil was found to be effective in reducing platelet aggregates formation in the retired breeder rat as determined using the platelet aggregate ratio method (PAR) with an ED50 of 16.1 mg/kg 24 hours post administration. In contrast to the hypothesis that 5-HT depletion is involved in the anti-aggregatory mechanism of suloctidil, no correlation was found between platelet 5- HT content and this antiplatelet activity. Reduction of platelet 5-HT content required multiple injections of high doses (100 mg/kg/day) of suloctidil. Suloctidil administration for 8 days at 100 mg/kg/day, which lowered platelet 5-HT content by 50%, resulted in no permanent effect on ex vivo platelet 5-HT uptake or thrombin-induced release, nor alteration in the plasma 5-HT level. However, these platelets exhibited a short-lived, significant increase in percent leakage of 5-HT after 30 minutes of incubation. Therefore, suloctidil treatment at high doses may with time result in platelet 5-HT depletion, however this effect is probably not related to the primary anti-aggregatory activity of the drug.

Daunorubicin and Platelet Function

1981 ◽  
Vol 45 (01) ◽  
pp. 038-042 ◽  
Author(s):  
M E Pogliani ◽  
R Fantasia ◽  
G Lambertenghi-Deliliers ◽  
E Cofrancesco
Keyword(s):  
Electron Microscope ◽  
Cellular Membrane ◽  
Hemorrhagic Diathesis ◽  
Clot Retraction ◽  
Freezing And Thawing ◽  
Platelet Factor ◽  
High Doses ◽  
Very High ◽  
Platelet Functions

SummaryThe influence of Daunorubicin on some platelet functions in vitro was investigated, using different concentrations of the drug (0.01-0.02-0.04 μg/ml). Daunorubicin was shown to inhibit Collagen and Thrombin induced platelet aggregation and the intensity of inhibition depended on both drug concentration and the time of preincubation.Daunorubicin was also shown to inhibit the release reaction, the platelet prostaglandin pathway and the availability platelet factor 3; the drug at concentrations for clinical use does not damage the platelet membrane, as is the case with the freezing and thawing test, in platelet uptake of 14C-serotonin and as confirmed by the electron microscope. When very high doses (0.16 mg) of Daunorubicin are used, lysis of the platelets can be observed and this is confirmed under the electron microscope by the presence of empty platelets with fractures at the level of the cytoplasmic membrane.Finally, Daunorubicin causes irreversible inhibition of reptilase clot-retraction, even if this is less severe than with Vincristine. Working with gel-filtered platelets, it would appear that the inhibition exercised by the drug on platelet reactions is not caused through modifications in Ca++ metabolism.The authors suggest that Daunorubicin, at the dosages used clinically, induces in vitro thrombocytopathy without damaging the cellular membrane as confirmed by the electron microscope.This impairment of platelet functions could play a part in hemorrhagic diathesis observed during Daunorubicin therapy.

Effects of Heparin Oligosaccharides with High Affinity for Antithrombin III in Experimental Venous Thrombosis

1982 ◽  
Vol 47 (03) ◽  
pp. 244-248 ◽  
Author(s):  
D P Thomas ◽  
Rosemary E Merton ◽  
T W Barrowcliffe ◽  
L Thunberg ◽  
U Lindahl
Keyword(s):  
Antithrombin Iii ◽  
Specific Activity ◽  
High Specific Activity ◽  
Factor Xa ◽  
Blood Levels ◽  
Thrombin Time ◽  
High Affinity ◽  
Very High

SummaryThe in vitro and in vivo characteristics of two oligosaccharide heparin fragments have been compared to those of unfractionated mucosal heparin. A decasaccharide fragment had essentially no activity by APTT or calcium thrombin time assays in vitro, but possessed very high specific activity by anti-Factor Xa assays. When injected into rabbits at doses of up to 80 ¼g/kg, this fragment was relatively ineffective in impairing stasis thrombosis despite producing high blood levels by anti-Xa assays. A 16-18 monosaccharide fragment had even higher specific activity (almost 2000 iu/mg) by chromogenic substrate anti-Xa assay, with minimal activity by APTT. When injected in vivo, this fragment gave low blood levels by APTT, very high anti-Xa levels, and was more effective in preventing thrombosis than the decasaccharide fragment. However, in comparison with unfractionated heparin, the 16-18 monosaccharide fragment was only partially effective in preventing thrombosis, despite producing much higher blood levels by anti-Xa assays.It is concluded that the high-affinity binding of a heparin fragment to antithrombin III does not by itself impair venous thrombogenesis, and that the anti-Factor Xa activity of heparin is only a partial expression of its therapeutic potential.

Carbon dots derived from Fusobacterium nucleatum for intracellular determination of Fe3+ and bioimaging both in vitro and in vivo

2021 ◽  
Author(s):  
Lijuan Liu ◽  
Shengting Zhang ◽  
Xiaodan Zheng ◽  
Hongmei Li ◽  
Qi Chen ◽  
...  
Keyword(s):  
Carbon Dots ◽  
Fusobacterium Nucleatum ◽  
Living Cells ◽  
First Time ◽  
Fluorescent Carbon Dots ◽  
Fluorescent Carbon

Fusobacterium nucleatum has been employed for the first time to synthesize fluorescent carbon dots which could be applied for the determination of Fe3+ ions in living cells and bioimaging in vitro and in vivo with excellent biocompatibility.

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