RETARDED BIOSYNTHESIS OF THYROGLOBULIN SUBUNITS AND THEIR POLYMERIZATION IN VITRO AFTER SUPPRESSION OF TSH SECRETION IN RATS BY CHRONIC ADMINISTRATION OF EXCESS THYROXINE IN THE FORM OF IODINATED CASEIN

1978 ◽  
Vol 89 (1) ◽  
pp. 108-121
Author(s):  
J. Sinadinović ◽  
M. Krainčanić ◽  
G. Kostić ◽  
M. Jovanović
Keyword(s):  
Chronic Administration ◽  
Thyroxine Treatment ◽  
Time Period ◽  
Tsh Secretion ◽  
Long Time ◽  
Pre Treatment ◽  
Reduced Rate

ABSTRACT The effects of short- and long-term (from 3 days to 28 weeks) administration of excess thyroxine in the form of the iodinated casein "Protamone" (0.2%) to rats on the content of soluble thyroid iodoproteins and on biosynthesis and polymerization of thyroid proteins in vitro were investigated. The concentration of soluble iodoproteins significantly increased (40–80%) up to 2 weeks of treatment, and after that remained at the same level. 27S iodoprotein markedly increased during thyroxine treatment. The content of DNA in the gland and the thyroid weight were a little lower in the treated rats than in the control. The incorporation rate of [14C]leucine into soluble and microsome-bound proteins in vitro was markedly reduced in the treated animals (30–80 % of control). Thyroxine pre-treatment of rats induced retarded synthesis of thyroglobulin and its subunits in vitro. The inhibition of the synthesis of thyroid proteins in vitro and the incrrease in the soluble iodopritein content in the gland in vivo was not correlated with the duration of thyroxine treatment. The immobilization of pre-formed thyroglobulin in the follicle lumen for a long time period is probably an important factor in the enlarged conversion of thyroglobulin into 27S iodoprotein. In conclusion, the long-term suppression of endogenous TSH secretion by administration of thyroxine results in an accumulation of iodoproteins in the thyroid and a reduced rate of synthesis of iodoproteins; after 2 weeks a steady state is reached both with regard to iodoprotein accumulation and synthesis. Finally, the results obtained suggest that the thyroid-pituitary axis becomes adapted to chronic administration of excess thyroxine.

scholarly journals Long-term fasting decreases mitochondrial avian UCP-mediated oxygen consumption in hypometabolic king penguins

2008 ◽  
Vol 295 (1) ◽  
pp. R92-R100 ◽  
Author(s):  
Benjamin Rey ◽  
Lewis G. Halsey ◽  
Virginie Dolmazon ◽  
Jean-Louis Rouanet ◽  
Damien Roussel ◽  
...  
Keyword(s):  
Oxygen Consumption ◽  
Metabolic Rate ◽  
Metabolic Efficiency ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
The Difference ◽  
Reduced Rate

In endotherms, regulation of the degree of mitochondrial coupling affects cell metabolic efficiency. Thus it may be a key contributor to minimizing metabolic rate during long periods of fasting. The aim of the present study was to investigate whether variation in mitochondrial avian uncoupling proteins (avUCP), as putative regulators of mitochondrial oxidative phosphorylation, may contribute to the ability of king penguins ( Aptenodytes patagonicus) to withstand fasting for several weeks. After 20 days of fasting, king penguins showed a reduced rate of whole animal oxygen consumption (V̇o2; −33%) at rest, together with a reduced abundance of avUCP and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1-α) mRNA in pectoralis muscle (−54%, −36%, respectively). These parameters were restored after the birds had been refed for 3 days. Furthermore, in recently fed, but not in fasted penguins, isolated muscle mitochondria showed a guanosine diphosphate-inhibited, fatty acid plus superoxide-activated respiration, indicating the presence of a functional UCP. It was calculated that variation in mitochondrial UCP-dependent respiration in vitro may contribute to nearly 20% of the difference in resting V̇o2 between fed or refed penguins and fasted penguins measured in vivo. These results suggest that the lowering of avUCP activity during periods of long-term energetic restriction may contribute to the reduction in metabolic rate and hence the ability of king penguins to face prolonged periods of fasting.

INFLUENCE OF CHLOROPHENOXYISOBUTYRATE (CPIB) ON THYROID PARAMETERS

1969 ◽  
Vol 60 (2) ◽  
pp. 294-302 ◽  
Author(s):  
J. Mølholm Hansen
Keyword(s):  
Free Thyroxine ◽  
Term Therapy ◽  
Low Doses ◽  
Testosterone Metabolism ◽  
Pre Treatment ◽  
Long Term Therapy ◽  
Higher Doses

ABSTRACT Chlorophenoxyisobutyrate (CPIB) added to serum in vitro increases the quantity of dialysable thyroxine. The same effect can be obtained in vivo following large doses of the preparation. After low doses, increase in serum proteinbound iodine (PBI) is observed and with higher doses this increase is not observed, probably because of the thyroxine-displacing effect. Free thyroxine increases in practically all patients investigated. In long-term treated patients the alterations in dialysable thyroxine, serum proteinbound iodine and free thyroxine are transient; pre-treatment values being regained in the course of ½–4 months. 131I uptake in the thyroid gland is influenced irregularly and transiently possibly via inhibition of the thyrotrophin production in the hypophysis. The effect of CPIB on serum cholesterol appears, in long-term therapy, to be completely independent of the effect on these thyroid parameters. This observation is also supported by the fact that the 14C-testosterone metabolism is normal in patients receiving long-term therapy.

Aluminium Kinetics during Haemodialysis with the Redy 2000 Sorbsystem

1989 ◽  
Vol 12 (11) ◽  
pp. 683-687 ◽  
Author(s):  
J.R. Curtis ◽  
B. Sampson
Keyword(s):  
Treatment Protocol ◽  
Hollow Fibre ◽  
Significant Rise ◽  
Aluminium Concentration ◽  
Pre Treatment ◽  
Kinetics Of ◽  
Long Term Studies

Aluminium kinetics of the Redy 2000 Sorbsystem using D3260 cartridges and the latest pre-treatment protocol have been studied in vitro and in vivo. In 7 patients, aluminium kinetics were studied during haemodialysis using the Redy 2000 Sorbysystem, D3260 cartridges, S557 acetate concentrate and Gambro hollow fibre dialyser (cuprophane 120M). The same patients were also studied during conventional haemodialysis using the Gambro AK10 proportionating system with acetate dialysate and Gambro hollow fibre dialyser (cuprophane 120M). There was no significant rise in plasma aluminium concentration during dialysis on the Redy 2000 Sorbsystem. The post-dialysis plasma aluminium concentrations were significantly higher after conventional haemodialysis, however, and the explanation for this is not clear but is not accounted for by differences in the degree of ultrafiltration during the studies. A significant rise in dialysate aluminium concentration was observed after 4 hours of dialysis on the Redy 2000 Sorbsystem. The manufacturer's ammonia test papers appear to be too insensitive as indicators of cartridge exhaustion and dialysate pH may be better. The D3260 cartridges should be used for a maximum of 4 hours only. Further long-term studies of aluminium kinetics using this system are justified.

Action of ADH on isolated medullary thick ascending limb of the Brattleboro rat

1986 ◽  
Vol 251 (2) ◽  
pp. F271-F277 ◽  
Author(s):  
K. Besseghir ◽  
M. E. Trimble ◽  
L. Stoner
Keyword(s):  
Chronic Administration ◽  
Osmotic Gradient ◽  
Thick Ascending Limb ◽  
Nacl Transport ◽  
Medullary Thick Ascending Limb ◽  
Gradual Process ◽  
Rapid Effect

Establishment of a maximal corticomedullary osmotic gradient during chronic administration of arginine vasopressin (antidiuretic hormone, ADH) to Brattleboro (diabetes insipidus, DI) rats is a gradual process. The effects of ADH on voltage and radioisotopic chloride efflux (lumen to bath) were investigated in medullary thick ascending limb (mTAL) isolated from DI rats and perfused in vitro. Acute in vitro exposure of mTAL to ADH (250 microU/ml) significantly increased both the voltage (+3.3 +/- 0.3 to +4.5 +/- 0.5 mV) and chloride efflux (192.7 +/- 29.4 to 240.4 +/- 41.5 peq/min X mm). After chronic in vivo treatment with ADH for 10-21 days mTAL expressed substantially higher basal voltage and chloride efflux (+8.4 +/- 0.6 mV and 393.2 +/- 71.6 peq/min X mm). Acute in vitro application of ADH to mTAL from chronically treated animals induced a further small increase in voltage (22%). These results are taken to indicate that ADH may have dual effects on NaCl transport by the mTAL of the DI rat: a small rapid effect, and a larger long-term increase in transport that can be shown only after chronic administration of ADH. These effects may, in part, explain the gradual enhancement of concentrating ability observed in DI rats.

The depressing (negative) effect of oestradiol benzoate on the in vitro secretion of LH and FSH by the pituitary gland of the LRH-pretreated long-term ovariectomized rat changes into the augmentative (positive) effect after discontinuation of the LRH-pretreatment

1985 ◽  
Vol 110 (3) ◽  
pp. 329-337 ◽  
Author(s):  
G. A. Schuiling ◽  
H. Moes ◽  
T. R. Koiter
Keyword(s):  
Depressing Effect ◽  
Ovx Rats ◽  
Gonadotrophin Secretion ◽  
Oestradiol Benzoate ◽  
Negative Effect ◽  
Positive Effect ◽  
Perifusion System

Abstract. The effect of pretreatment in vivo with oestradiol benzoate on in vitro secretion of LH and FSH was studied in long-term ovariectomized (OVX) rats both at the end of a 5-day continuous in vivo pretreatment with LRH and 4-days after cessation of such LRH pretreatment. Rats were on day 0 sc implanted with osmotic minipumps which released LRH at the rate of 250 ng/h. Control rats were implanted with a piece of silicone elastomer with the dimensions of a minipump. On days 2 and 4 the rats were injected with either 3 μg EB or with oil. On day 5 part of the rats were decapitated and the in vitro autonomous (i.e. non-LRH-stimulated) and 'supra-maximally' LRHstimulated release of LH and FSH was studied using a perifusion system. From other rats the minipumps were removed on day 5 and perifusion was performed on day 9. On the 5th day of the in vivo LRH pretreatment the pituitary LH/FSH stores were partially depleted; the pituitaries of the EB-treated rats more so than those of the oil-injected rats. EB alone had no significant effect on the content of the pituitary LH- and FSH stores. On day 9, i.e. 4 days after removal of the minipumps, the pituitary LH and FSH contents had increased in both the oil- and the EB injected rats, but had not yet recovered to control values. In rats not subjected to the 5-days pretreatment with LRH EB had a positive effect on the supra-maximally LRH-stimulated secretion of LH and FSH as well as on the non-stimulated secretion of LH. EB had no effect on the non-stimulated secretion of FSH. After 5 days of in vivo pretreatment with LRH only, the in vitro non-stimulated and supra-maximally LRH-stimulated secretion of both LH and FSH were strongly impaired, the effect correlating well with the LRH-induced depletion of the pituitary LH/FSH stores. In such LRH-pretreated rats EB had on day 5 a negative effect on the (already depressed) LRH-stimulated secretion of LH (not on that of FSH). EB had no effect on the non-stimulated LH/FSH secretion. It could be demonstrated that the negative effect of the combined LRH/EB pretreatment was mainly due to the depressing effect of this treatment on the pituitary LH and FSH stores: the effect of oestradiol on the pituitary LRH-responsiveness (release as related to pituitary gonadotrophin content) remained positive. In LRH-pretreated rats, however, this positive effect of EB was smaller than in rats not pretreated with LRH. Four days after removal of the minipumps there was again a positive effect of EB on the LRH-stimulated secretion of LH and FSH as well as on the non-stimulated secretion of LH. The positive effect of EB on the pituitary LRH-responsiveness was as strong as in rats which had not been exposed to exogenous LRH. The non-stimulated secretion of FSH was again not affected by EB. The results demonstrate that the effect of EB on the oestrogen-sensitive components of gonadotrophin secretion consists of two components: an effect on the pituitary LRH-responsiveness proper, and an effect on the pituitary LH/FSH stores. The magnitude of the effect of EB on the LRH-responsiveness is LRH dependent: it is very weak (almost zero) in LRH-pretreated rats, but strong in rats not exposed to LRH as well as in rats of which the LRH-pretreatment was stopped 4 days previously. Similarly, the effect of EB on the pituitary LH and FSH stores is LRH-dependent: in the absence of LRH, EB has no influence on the contents of these stores, but EB can potentiate the depleting effect of LRH on the LH/FSH-stores. Also this effect disappear after cessation of the LRH-pretreatment.

THE ROLE OF POLYETHYLENIMINE IN ENHANCING PERFORMANCE OF GLUTAMATE BIOSENSORS

2018 ◽  
Vol 8 (3) ◽  
pp. 36-41
Author(s):  
Diep Do Thi Hong ◽  
Duong Le Phuoc ◽  
Hoai Nguyen Thi ◽  
Serra Pier Andrea ◽  
Rocchitta Gaia
Keyword(s):  
First Generation ◽  
Good Reproducibility ◽  
Complex Matrices ◽  
Long Term Stability ◽  
In Vitro Characterization ◽  
Glutamate Oxidase

Background: The first biosensor was constructed more than fifty years ago. It was composed of the biorecognition element and transducer. The first-generation enzyme biosensors play important role in monitoring neurotransmitter and determine small quantities of substances in complex matrices of the samples Glutamate is important biochemicals involved in energetic metabolism and neurotransmission. Therefore, biosensors requires the development a new approach exhibiting high sensibility, good reproducibility and longterm stability. The first-generation enzyme biosensors play important role in monitoring neurotransmitter and determine small quantities of substances in complex matrices of the samples. The aims of this work: To find out which concentration of polyethylenimine (PEI) exhibiting the most high sensibility, good reproducibility and long-term stability. Methods: We designed and developed glutamate biosensor using different concentration of PEI ranging from 0% to 5% at Day 1 and Day 8. Results: After Glutamate biosensors in-vitro characterization, several PEI concentrations, ranging from 0.5% to 1% seem to be the best in terms of VMAX, the KM; while PEI content ranging from 0.5% to 1% resulted stable, PEI 1% displayed an excellent stability. Conclusions: In the result, PEI 1% perfomed high sensibility, good stability and blocking interference. Furthermore, we expect to develop and characterize an implantable biosensor capable of detecting glutamate, glucose in vivo. Key words: Glutamate biosensors, PEi (Polyethylenimine) enhances glutamate oxidase, glutamate oxidase biosensors

Strategies to Protect Hematopoietic Stem Cells from Culture-Induced Stress Conditions

2020 ◽  
Vol 15 ◽  
Author(s):  
Fatima Aerts-Kaya
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Ex Vivo ◽  
Stress Conditions ◽  
Stress Factors ◽  
Hematopoietic Stem ◽  
Induced Stress

: In contrast to their almost unlimited potential for expansion in vivo and despite years of dedicated research and optimization of expansion protocols, the expansion of Hematopoietic Stem Cells (HSCs) in vitro remains remarkably limited. Increased understanding of the mechanisms that are involved in maintenance, expansion and differentiation of HSCs will enable the development of better protocols for expansion of HSCs. This will allow procurement of HSCs with long-term engraftment potential and a better understanding of the effects of the external influences in and on the hematopoietic niche that may affect HSC function. During collection and culture of HSCs, the cells are exposed to suboptimal conditions that may induce different levels of stress and ultimately affect their self-renewal, differentiation and long-term engraftment potential. Some of these stress factors include normoxia, oxidative stress, extra-physiologic oxygen shock/stress (EPHOSS), endoplasmic reticulum (ER) stress, replicative stress, and stress related to DNA damage. Coping with these stress factors may help reduce the negative effects of cell culture on HSC potential, provide a better understanding of the true impact of certain treatments in the absence of confounding stress factors. This may facilitate the development of better ex vivo expansion protocols of HSCs with long-term engraftment potential without induction of stem cell exhaustion by cellular senescence or loss of cell viability. This review summarizes some of available strategies that may be used to protect HSCs from culture-induced stress conditions.

The Application of the Cold Atmospheric Plasma-Activated Solutions in Cancer Treatment

2018 ◽  
Vol 18 (6) ◽  
pp. 769-775 ◽  
Author(s):  
Dayun Yan ◽  
Jonathan H. Sherman ◽  
Michael Keidar
Keyword(s):  
Cancer Treatment ◽  
Atmospheric Plasma ◽  
Current Status ◽  
Cold Atmospheric Plasma ◽  
Anti Cancer ◽  
Long Time ◽  
Key Topics ◽  
The Common

Background: Over the past five years, the cold atmospheric plasma-activated solutions (PAS) have shown their promissing application in cancer treatment. Similar as the common direct cold plasma treatment, PAS shows a selective anti-cancer capacity in vitro and in vivo. However, different from the direct cold atmospheric plasma (CAP) treatment, PAS can be stored for a long time and can be used without dependence on a CAP device. The research on PAS is gradually becoming a hot topic in plasma medicine. Objectives: In this review, we gave a concise but comprehensive summary on key topics about PAS including the development, current status, as well as the main conclusions about the anti-cancer mechanism achieved in past years. The approaches to make strong and stable PAS are also summarized.

scholarly journals An ARF GTPase module promoting invasion and metastasis through regulating phosphoinositide metabolism

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Marisa Nacke ◽  
Emma Sandilands ◽  
Konstantina Nikolatou ◽  
Álvaro Román-Fernández ◽  
Susan Mason ◽  
...  
Keyword(s):  
Metastatic Cancer ◽  
Cellular Responses ◽  
Signalling Pathways ◽  
External Signal ◽  
Phosphoinositide Metabolism ◽  
Invasion And Metastasis ◽  
3 Dimensional

AbstractThe signalling pathways underpinning cell growth and invasion use overlapping components, yet how mutually exclusive cellular responses occur is unclear. Here, we report development of 3-Dimensional culture analyses to separately quantify growth and invasion. We identify that alternate variants of IQSEC1, an ARF GTPase Exchange Factor, act as switches to promote invasion over growth by controlling phosphoinositide metabolism. All IQSEC1 variants activate ARF5- and ARF6-dependent PIP5-kinase to promote PI(3,4,5)P3-AKT signalling and growth. In contrast, select pro-invasive IQSEC1 variants promote PI(3,4,5)P3 production to form invasion-driving protrusions. Inhibition of IQSEC1 attenuates invasion in vitro and metastasis in vivo. Induction of pro-invasive IQSEC1 variants and elevated IQSEC1 expression occurs in a number of tumour types and is associated with higher-grade metastatic cancer, activation of PI(3,4,5)P3 signalling, and predicts long-term poor outcome across multiple cancers. IQSEC1-regulated phosphoinositide metabolism therefore is a switch to induce invasion over growth in response to the same external signal. Targeting IQSEC1 as the central regulator of this switch may represent a therapeutic vulnerability to stop metastasis.

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.

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