Thyroid autonomy: sensitive detection in vivo and estimation of its functional relevance using quantified high-resolution scintigraphy

Abstract. This study is concerned with 236 euthyroid individuals living in an area of iodine deficiency, 227 of whom had endemic goitres. In these subjects, autonomy could be suspected owing to an inhomogeneous activity distribution on the thyroid scintigram or a subnormal TSH response to TRH. They complete a total number of 426 investigated individuals. Previously, in 190 separated controls without evidence of autonomy, the reference ranges for the thyroid 99mTc pertechnetate uptake under suppression (TcUs), a measure for the non-suppressible thyroid iodide clearance, and for suppressibility of circumscribed thyroid regions, had been determined. These two parameters obtained by highresolution quantified scintigraphy were used for an accurate detection of thyroid autonomy among the 236 individuals. Suppression scintigraphy revealed autonomy in 171 patients. ΔTSH after TRH was subnormal in 40% of the subjects with abnormal thyroid suppressibility. Prevalence of abnormal suppression was dependent on three factors: patient age, goitre type and estimated thyroid weight. In the total investigated collective, the prevalence of autonomy was 77% in patients with a goitre weight above 50 g. The individuals with abnormal suppression were grouped into four classes of TcUs. In these classes, free thyroxine index (FT4I) and total triiodothyronine (TT3) increased with increasing TcUs, whereas ΔTSH decreased. This finding indicates a continuum of different extents of autonomous thyroid function, whereas in the individual patient, the extent can be determined using the pertechnetate uptake under suppression. In addition, FT4I, TT3 and ΔTSH in each of the TcUs classes depended on the individual iodine supply. It is concluded that, in patients with thyroid autonomy, actual thyroid hormone concentrations and TSH stimulation are determined by two major factors: the extent of autonomy and the individual iodine supply. Therefore, in iodine deficiency, the TRH test may be normal, although autonomy is present. This relationship explains the reduced sensitivity of the TRH test to detect autonomy in iodine-deficient goitres.

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Physiological aspects of the thyroid trapping function and its suppression in iodine deficiency using 99m Tc pertechnetate

Acta Endocrinologica ◽

10.1530/acta.0.1150175 ◽

1987 ◽

Vol 115 (2) ◽

pp. 175-182 ◽

Cited By ~ 11

Author(s):

Manfred Bähre ◽

Reinhard Hilgers ◽

Corinna Lindemann ◽

Dieter Emrich

Keyword(s):

Iodine Deficiency ◽

Reference Range ◽

Control Group ◽

Reference Ranges ◽

Oestrogen Treatment ◽

Factors Affecting ◽

Iodine Supply ◽

Small Influence ◽

Iodine Contamination

Abstract. In an area of iodine deficiency, we investigated 190 individuals with and without euthyroid endemic goitre, who had a normal TSH response after TRH and an entirely homogeneous thyroid scintigram before and under suppression. In these subjects, the thyroid uptake of 99mTc pertechnetate, as a measure of the iodide trapping function, was determined before (TcUb) and under suppression (TcUs), using quantitatively evaluated scintigraphy. In this control group of individuals, without evidence of autonomy, the reference ranges of TcUb and TcUs were determined. The upper limit of the reference range for TcUb was 7.4% of the tracer activity injected, and for TcUs 1.6%. The reference range of TcUs is to be used to detect accurately thyroid autonomy in vivo. In addition, factors affecting the thyroid trapping function were investigated. With decreased iodine supply, trapping before suppression was increased, compensating for iodine deficiency. The effect of TSH on the trapping function was secondary, indicating that, to a considerable degree, the follicular cells adapt their iodide trapping to the iodine supply. The trapping before and under suppression increased with the estimated thyroid weight. ΔTSH after TRH stimulation measured before suppression correlated inversely with the trapping under suppression. The two latter observations suggest that there is a continuum between low and increased levels of the TSH-independent thyroid function, even among these selected individuals without primary evidence of autonomous tissue. A correlation of the trapping function with sex, oestrogen treatment, and goitre type was not demonstrable. Age was found to have a small influence. Except for iodine contamination, the factors affecting the pertechnetate uptake of the thyroid, can be neglected under routine conditions.

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Influence of stable iodine on the uptake of the thyroid – model vs. experiment

Nuklearmedizin ◽

10.1055/s-0038-1623989 ◽

2001 ◽

Vol 40 (01) ◽

pp. 31-37 ◽

Cited By ~ 1

Author(s):

U. Wellner ◽

E. Voth ◽

H. Schicha ◽

K. Weber

Keyword(s):

Time Course ◽

Compartment Model ◽

The Body ◽

Iodine Uptake ◽

Model Calculations ◽

Physiological Conditions ◽

Iodine Supply ◽

Predicted Values ◽

The Individual ◽

Stable Iodine

Summary Aim: The influence of physiological and pharmacological amounts of iodine on the uptake of radioiodine in the thyroid was examined in a 4-compartment model. This model allows equations to be derived describing the distribution of tracer iodine as a function of time. The aim of the study was to compare the predictions of the model with experimental data. Methods: Five euthyroid persons received stable iodine (200 μg, 10 mg). 1-123-uptake into the thyroid was measured with the Nal (Tl)-detector of a body counter under physiological conditions and after application of each dose of additional iodine. Actual measurements and predicted values were compared, taking into account the individual iodine supply as estimated from the thyroid uptake under physiological conditions and data from the literature. Results: Thyroid iodine uptake decreased from 80% under physiological conditions to 50% in individuals with very low iodine supply (15 μg/d) (n = 2). The uptake calculated from the model was 36%. Iodine uptake into the thyroid did not decrease in individuals with typical iodine supply, i.e. for Cologne 65-85 μg/d (n = 3). After application of 10 mg of stable iodine, uptake into the thyroid decreased in all individuals to about 5%, in accordance with the model calculations. Conclusion: Comparison of theoretical predictions with the measured values demonstrated that the model tested is well suited for describing the time course of iodine distribution and uptake within the body. It can now be used to study aspects of iodine metabolism relevant to the pharmacological administration of iodine which cannot be investigated experimentally in humans for ethical and technical reasons.

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Platelet Microtubules in Clot Structure Formation and Contractile Force Generation: Investigation of a Controversy

Thrombosis and Haemostasis ◽

10.1055/s-0038-1661596 ◽

1986 ◽

Vol 56 (01) ◽

pp. 023-027 ◽

Cited By ~ 9

Author(s):

C J Jen ◽

L V McIntire

Keyword(s):

Network Formation ◽

Contractile Force ◽

Second Phase ◽

Clot Retraction ◽

Forming Process ◽

Microtubule Organization ◽

Physiological Processes ◽

Fibrin Network ◽

Two Parameters

SummaryWhether platelet microtubules are involved in clot retraction/ contraction has been controversial. To address this question we have simultaneously measured two clotting parameters, clot structural rigidity and isometric contractile force, using a rheological technique. For recalcified PRP clots these two parameters began rising together at about 15 min after CaCl2 addition. In the concentration range affecting microtubule organization in platelets, colchicine, vinca alkaloids and taxol demonstrated insignificant effects on both clotting parameters of a recalcified PRP clot. For PRP clots induced by adding small amounts of exogenous thrombin, the kinetic curves of clot rigidity were biphasic and without a lag time. The first phase corresponded to a platelet-independent network forming process, while the second phase corresponded to a platelet-dependent process. These PRP clots began generating contractile force at the onset of the second phase. For both rigidity and force parameters, only the second phase of clotting kinetics was retarded by microtubule affecting reagents. When PRP samples were clotted by adding a mixture of CaCl2 and thrombin, the second phase clotting was accelerated and became superimposed on the first phase. The inhibitory effects of micro tubule affecting reagents became less pronounced. Thrombin clotting of a two-component system (washed platelets/ purified fibrinogen) was also biphasic, with the second phase being microtubule-dependent. In conclusion, platelet microtubules are important in PRP clotted with low concentrations of thrombin, during which fibrin network formation precedes platelet-fibrin interactions. On the other hand they are unimportant if a PRP clot is induced by recalcification, during which the fibrin network is constructed in the presence of platelet-fibrin interactions. The latter is likely to be more analogous to physiological processes in vivo.

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Preclinical Testing of Radiopharmaceuticals for the Detection and Characterization of Osteomyelitis: Experiences from a Porcine Model

Molecules ◽

10.3390/molecules26144221 ◽

2021 ◽

Vol 26 (14) ◽

pp. 4221

Author(s):

Aage Kristian Olsen Alstrup ◽

Svend Borup Jensen ◽

Ole Lerberg Nielsen ◽

Lars Jødal ◽

Pia Afzelius

Keyword(s):

Animal Model ◽

Animal Models ◽

Porcine Model ◽

Animal Experiments ◽

Radioactive Tracers ◽

The Individual ◽

Selection Of

The development of new and better radioactive tracers capable of detecting and characterizing osteomyelitis is an ongoing process, mainly because available tracers lack selectivity towards osteomyelitis. An integrated part of developing new tracers is the performance of in vivo tests using appropriate animal models. The available animal models for osteomyelitis are also far from ideal. Therefore, developing improved animal osteomyelitis models is as important as developing new radioactive tracers. We recently published a review on radioactive tracers. In this review, we only present and discuss osteomyelitis models. Three ethical aspects (3R) are essential when exposing experimental animals to infections. Thus, we should perform experiments in vitro rather than in vivo (Replacement), use as few animals as possible (Reduction), and impose as little pain on the animal as possible (Refinement). The gain for humans should by far exceed the disadvantages for the individual experimental animal. To this end, the translational value of animal experiments is crucial. We therefore need a robust and well-characterized animal model to evaluate new osteomyelitis tracers to be sure that unpredicted variation in the animal model does not lead to a misinterpretation of the tracer behavior. In this review, we focus on how the development of radioactive tracers relies heavily on the selection of a reliable animal model, and we base the discussions on our own experience with a porcine model.

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Animal Models in the Evaluation of the Effectiveness of Phage Therapy for Infections Caused by Gram-Negative Bacteria from the ESKAPE Group and the Reliability of Its Use in Humans

Microorganisms ◽

10.3390/microorganisms9020206 ◽

2021 ◽

Vol 9 (2) ◽

pp. 206

Author(s):

Martyna Cieślik ◽

Natalia Bagińska ◽

Andrzej Górski ◽

Ewa Jończyk-Matysiak

Keyword(s):

Animal Models ◽

Phage Therapy ◽

Animal Experiments ◽

Species Group ◽

Effectiveness Evaluation ◽

Gram Negative Bacteria ◽

Gram Negative ◽

Enterobacter Species ◽

The Individual

The authors emphasize how extremely important it is to highlight the role played by animal models in an attempt to determine possible phage interactions with the organism into which it was introduced as well as to determine the safety and effectiveness of phage therapy in vivo taking into account the individual conditions of a given organism and its physiology. Animal models in which phages are used make it possible, among other things, to evaluate the effective therapeutic dose and to choose the possible route of phage administration depending on the type of infection developed. These results cannot be applied in detail to the human body, but the knowledge gained from animal experiments is invaluable and very helpful. We would like to highlight how useful animal models may be for the possible effectiveness evaluation of phage therapy in the case of infections caused by gram-negative bacteria from the ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter species) group of pathogens. In this review, we focus specifically on the data from the last few years.

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Graphene and Reproduction: A Love-Hate Relationship

Nanomaterials ◽

10.3390/nano11020547 ◽

2021 ◽

Vol 11 (2) ◽

pp. 547

Author(s):

Marina Ramal-Sanchez ◽

Antonella Fontana ◽

Luca Valbonetti ◽

Alessandra Ordinelli ◽

Nicola Bernabò ◽

...

Keyword(s):

Graphene Oxide ◽

Reproductive Function ◽

Scientometric Analysis ◽

Potential Toxicity ◽

Good Tool ◽

Vitro Fertilization ◽

Number Of Publications ◽

The Individual

Since its discovery, graphene and its multiple derivatives have been extensively used in many fields and with different applications, even in biomedicine. Numerous efforts have been made to elucidate the potential toxicity derived from their use, giving rise to an adequate number of publications with varied results. On this basis, the study of the reproductive function constitutes a good tool to evaluate not only the toxic effects derived from the use of these materials directly on the individual, but also the potential toxicity passed on to the offspring. By providing a detailed scientometric analysis, the present review provides an updated overview gathering all the research studies focused on the use of graphene and graphene-based materials in the reproductive field, highlighting the consequences and effects reported to date from experiments performed in vivo and in vitro and in different animal species (from Archea to mammals). Special attention is given to the oxidized form of graphene, graphene oxide, which has been recently investigated for its ability to increase the in vitro fertilization outcomes. Thus, the potential use of graphene oxide against infertility is hypothesized here, probably by engineering the spermatozoa and thus manipulating them in a safer and more efficient way.

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ANTI-INFLAMMATORY ACTIVITY OF CURCUMIN AND CAPSAICIN AUGMENTED IN COMBINATION

International Journal of Pharmacy and Pharmaceutical Sciences ◽

10.22159/ijpps.2017v9i6.18635 ◽

2017 ◽

Vol 9 (6) ◽

pp. 145

Author(s):

Thriveni Vasanth Kumar ◽

Manjunatha H. ◽

Rajesh Kp

Keyword(s):

Acetic Acid ◽

Protective Effect ◽

Vascular Permeability ◽

Diclofenac Sodium ◽

Significant Inhibition ◽

Inflammatory Activity ◽

Anti Inflammatory ◽

The Individual

Objective: Dietary curcumin and capsaicin are well known for their health beneficial potencies. The current study was done to assess the anti-inflammatory activity of curcumin, capsaicin and their combination by employing in vitro and in vivo models.Methods: We investigated the protective effect of curcumin, capsaicin and their combination using in vitro heat induced human red blood cell (HRBC) membrane stabilisation, in vivo 3% agar induced leukocyte mobilisation and acetic acid induced vascular permeability assay.Results: Curcumin, capsaicin and their combination exhibited concentration dependent protective effect against heat-induced HRBC membrane destabilisation, while combined curcumin and capsaicin restored 87.0±0.64 % membrane stability and it is found to be better than curcumin, capsaicin and diclofenac sodium (75.0±0.25. 72±0.9 and 80.0±0.31 %) protective effect. In agar suspension induced leukocyte mobilization assay, the combined curcumin and capsaicin had shown 39.5±1.58 % of inhibition compared to individual curcumin and capsaicin, which showed moderate inhibition of 16.0±3.14 and 21.6±2.17 % respectively. Besides, the combined curcumin and capsaicin had shown highly significant inhibition of acetic acid-induced vascular permeability in rats (62.0±3.14 %), whereas individual curcumin and capsaicin showed moderate inhibition of vascular permeability with 36.0±2.41 and 43.0±1.92 % respectively.Conclusion: This study demonstrates the significant anti-inflammatory property of combined curcumin and capsaicin at half of the individual concentration of curcumin and capsaicin.

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In Vivo Bioavailability of Selenium in Selenium-Enriched Streptococcus thermophilus and Enterococcus faecium in CD IGS Rats

Antioxidants ◽

10.3390/antiox10030463 ◽

2021 ◽

Vol 10 (3) ◽

pp. 463

Author(s):

Gabriela Krausova ◽

Antonin Kana ◽

Marek Vecka ◽

Ivana Hyrslova ◽

Barbora Stankova ◽

...

Keyword(s):

Glutathione Reductase ◽

Enterococcus Faecium ◽

Reductase Activity ◽

Streptococcus Thermophilus ◽

Heart Tissue ◽

Sprague Dawley ◽

Glutathione Reductase Activity ◽

Novel Concept ◽

The Individual

The selenium (Se) enrichment of yeasts and lactic acid bacteria (LAB) has recently emerged as a novel concept; the individual health effects of these beneficial microorganisms are combined by supplying the essential micronutrient Se in a more bioavailable and less toxic form. This study investigated the bioavailability of Se in the strains Enterococcus faecium CCDM 922A (EF) and Streptococcus thermophilus CCDM 144 (ST) and their respective Se-enriched forms, SeEF and SeST, in a CD (SD-Sprague Dawley) IGS rat model. Se-enriched LAB administration resulted in higher Se concentrations in the liver and kidneys of rats, where selenocystine was the prevalent Se species. The administration of both Se-enriched strains improved the antioxidant status of the animals. The effect of the diet was more pronounced in the heart tissue, where a lower glutathione reductase content was observed, irrespective of the Se fortification in LAB. Interestingly, rats fed diets with EF and SeEF had higher glutathione reductase activity. Reduced concentrations of serum malondialdehyde were noted following Se supplementation. Diets containing Se-enriched strains showed no macroscopic effects on the liver, kidneys, heart, and brain and had no apparent influence on the basic parameters of the lipid metabolism. Both the strains tested herein showed potential for further applications as promising sources of organically bound Se and Se nanoparticles.

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Signal Integration in Quorum Sensing Enables Cross-Species Induction of Virulence in Pectobacterium wasabiae

mBio ◽

10.1128/mbio.00398-17 ◽

2017 ◽

Vol 8 (3) ◽

Cited By ~ 13

Author(s):

Rita S. Valente ◽

Pol Nadal-Jimenez ◽

André F. P. Carvalho ◽

Filipe J. D. Vieira ◽

Karina B. Xavier

Keyword(s):

Signal Transduction ◽

Quorum Sensing ◽

Plant Pathogen ◽

Bacterial Species ◽

Homoserine Lactone ◽

Signal Molecules ◽

Acyl Homoserine Lactone ◽

Interspecies Interactions ◽

Major Factors

ABSTRACT Bacterial communities can sense their neighbors, regulating group behaviors in response to cell density and environmental changes. The diversity of signaling networks in a single species has been postulated to allow custom responses to different stimuli; however, little is known about how multiple signals are integrated and the implications of this integration in different ecological contexts. In the plant pathogen Pectobacterium wasabiae (formerly Erwinia carotovora), two signaling networks—the N-acyl homoserine lactone (AHL) quorum-sensing system and the Gac/Rsm signal transduction pathway—control the expression of secreted plant cell wall-degrading enzymes, its major virulence determinants. We show that the AHL system controls the Gac/Rsm system by affecting the expression of the regulatory RNA RsmB. This regulation is mediated by ExpR2, the quorum-sensing receptor that responds to the P. wasabiae cognate AHL but also to AHLs produced by other bacterial species. As a consequence, this level of regulation allows P. wasabiae to bypass the Gac-dependent regulation of RsmB in the presence of exogenous AHLs or AHL-producing bacteria. We provide in vivo evidence that this pivotal role of RsmB in signal transduction is important for the ability of P. wasabiae to induce virulence in response to other AHL-producing bacteria in multispecies plant lesions. Our results suggest that the signaling architecture in P. wasabiae was coopted to prime the bacteria to eavesdrop on other bacteria and quickly join the efforts of other species, which are already exploiting host resources. IMPORTANCE Quorum-sensing mechanisms enable bacteria to communicate through small signal molecules and coordinate group behaviors. Often, bacteria have various quorum-sensing receptors and integrate information with other signal transduction pathways, presumably allowing them to respond to different ecological contexts. The plant pathogen Pectobacterium wasabiae has two N-acyl homoserine lactone receptors with apparently the same regulatory functions. Our work revealed that the receptor with the broadest signal specificity is also responsible for establishing the link between the main signaling pathways regulating virulence in P. wasabiae. This link is essential to provide P. wasabiae with the ability to induce virulence earlier in response to higher densities of other bacterial species. We further present in vivo evidence that this novel regulatory link enables P. wasabiae to join related bacteria in the effort to degrade host tissue in multispecies plant lesions. Our work provides support for the hypothesis that interspecies interactions are among the major factors influencing the network architectures observed in bacterial quorum-sensing pathways. IMPORTANCE Quorum-sensing mechanisms enable bacteria to communicate through small signal molecules and coordinate group behaviors. Often, bacteria have various quorum-sensing receptors and integrate information with other signal transduction pathways, presumably allowing them to respond to different ecological contexts. The plant pathogen Pectobacterium wasabiae has two N-acyl homoserine lactone receptors with apparently the same regulatory functions. Our work revealed that the receptor with the broadest signal specificity is also responsible for establishing the link between the main signaling pathways regulating virulence in P. wasabiae. This link is essential to provide P. wasabiae with the ability to induce virulence earlier in response to higher densities of other bacterial species. We further present in vivo evidence that this novel regulatory link enables P. wasabiae to join related bacteria in the effort to degrade host tissue in multispecies plant lesions. Our work provides support for the hypothesis that interspecies interactions are among the major factors influencing the network architectures observed in bacterial quorum-sensing pathways.

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Synthetic Riboswitches for the Analysis of tRNA Processing by eukaryotic RNase P Enzymes

RNA ◽

10.1261/rna.078814.121 ◽

2022 ◽

pp. rna.078814.121

Author(s):

Anna Ender ◽

Nadine Grafl ◽

Tim Kolberg ◽

Sven Findeiss ◽

Peter F. Stadler ◽

...

Keyword(s):

Homo Sapiens ◽

Rnase P ◽

Single Stranded Region ◽

Domains Of Life ◽

The Individual ◽

The Impact ◽

Individual Enzyme ◽

Trna Precursor

Removal of the 5' leader region is an essential step in the maturation of tRNA molecules in all domains of life. This reaction is catalyzed by various RNase P activities, ranging from ribonucleoproteins with ribozyme activity to protein-only forms. In Escherichia coli, the efficiency of RNase P mediated cleavage can be controlled by computationally designed riboswitch elements in a ligand-dependent way, where the 5' leader sequence of a tRNA precursor is either sequestered in a hairpin structure or presented as a single-stranded region accessible for maturation. In the presented work, the regulatory potential of such artificial constructs is tested on different forms of eukaryotic RNase P enzymes – two protein-only RNase P enzymes (PRORP1 and PRORP2) from Arabidopsis thaliana and the ribonucleoprotein of Homo sapiens. The PRORP enzymes were analyzed in vitro as well as in vivo in a bacterial RNase P complementation system. We also tested in HEK293T cells whether the riboswitches remain functional with human nuclear RNase P. While the regulatory principle of the synthetic riboswitches applies for all tested RNase P enzymes, the results also show differences in the substrate requirements of the individual enzyme versions. Hence, such designed RNase P riboswitches represent a novel tool to investigate the impact of the structural composition of the 5'-leader on substrate recognition by different types of RNase P enzymes.

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