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Статті в журналах з теми "T1AM"
1
Rogowski, Michael, Lorenza Bellusci, Martina Sabatini, Simona Rapposelli, Shaikh M. Rahman, Grazia Chiellini, and Fariba M. Assadi-Porter. "Lipolytic Effects of 3-Iodothyronamine (T1AM) and a Novel Thyronamine-Like Analog SG-2 through the AMPK Pathway." International Journal of Molecular Sciences 20, no. 16 (August 20, 2019): 4054. http://dx.doi.org/10.3390/ijms20164054.
Повний текст джерелаАнотація:
3-Iodothyronamine (T1AM) and its synthetic analog SG-2 are rapidly emerging as promising drivers of cellular metabolic reprogramming. Our recent research indicates that in obese mice a sub-chronic low dose T1AM treatment increased lipolysis, associated with significant weight loss independent of food consumption. The specific cellular mechanism of T1AM’s lipolytic effect and its site of action remains unknown. First, to study the mechanism used by T1AM to gain entry into cells, we synthesized a fluoro-labeled version of T1AM (FL-T1AM) by conjugating it to rhodamine (TRITC) and analyzed its cellular uptake and localization in 3T3-L1 mouse adipocytes. Cell imaging using confocal microscopy revealed a rapid intercellular uptake of FL-T1AM into mitochondria without localization to the lipid droplet or nucleus of mature adipocytes. Treatment of 3T3-L1 adipocytes with T1AM and SG-2 resulted in decreased lipid accumulation, the latter showing a significantly higher potency than T1AM (10 µM vs. 20 µM, respectively). We further examined the effects of T1AM and SG-2 on liver HepG2 cells. A significant decrease in lipid accumulation was observed in HepG2 cells treated with T1AM or SG-2, due to increased lipolytic activity. This was confirmed by accumulation of glycerol in the culture media and through activation of the AMPK/ACC signaling pathways.
2
Saba, Alessandro, Grazia Chiellini, Sabina Frascarelli, Maja Marchini, Sandra Ghelardoni, Andrea Raffaelli, Massimo Tonacchera, Paolo Vitti, Thomas S. Scanlan, and Riccardo Zucchi. "Tissue Distribution and Cardiac Metabolism of 3-Iodothyronamine." Endocrinology 151, no. 10 (August 25, 2010): 5063–73. http://dx.doi.org/10.1210/en.2010-0491.
Повний текст джерелаАнотація:
3-Iodothyronamine (T1AM) is a novel relative of thyroid hormone, able to interact with specific G protein-coupled receptors, known as trace amine-associated receptors. Significant functional effects are produced by exogenous T1AM, including a negative inotropic and chronotropic effect in cardiac preparations. This work was aimed at estimating endogenous T1AM concentration in different tissues and determining its cardiac metabolism. A novel HPLC tandem mass spectrometry assay was developed, allowing detection of T1AM, thyronamine, 3-iodothyroacetic acid, and thyroacetic acid. T1AM was detected in rat serum, at the concentration of 0.3 ± 0.03 pmol/ml, and in all tested organs (heart, liver, kidney, skeletal muscle, stomach, lung, and brain), at concentrations significantly higher than the serum concentration, ranging from 5.6 ± 1.5 pmol/g in lung to 92.9 ± 28.5 pmol/g in liver. T1AM was also identified for the first time in human blood. In H9c2 cardiomyocytes and isolated perfused rat hearts, significant Na+-dependent uptake of exogenous T1AM was observed, and at the steady state total cellular or tissue T1AM concentration exceeded extracellular concentration by more than 20-fold. In both preparations T1AM underwent oxidative deamination to 3-iodothyroacetic acid. T1AM deamination was inhibited by iproniazid but not pargyline or semicarbazide, suggesting the involvement of both monoamine oxidase and semicarbazide-sensitive amine oxidase. Thyronamine and thyroacetic acid were not detected in heart. Finally, evidence of T1AM production was observed in cardiomyocytes exposed to exogenous thyroid hormone, although the activity of this pathway was very low.
3
Dinter, Juliane, Noushafarin Khajavi, Jessica Mühlhaus, Carolin Leonie Wienchol, Maxi Cöster, Thomas Hermsdorf, Claudia Stäubert та ін. "The Multitarget Ligand 3-Iodothyronamine Modulates β-Adrenergic Receptor 2 Signaling". European Thyroid Journal 4, Suppl. 1 (2015): 21–29. http://dx.doi.org/10.1159/000381801.
Повний текст джерелаАнотація:
Background: 3-Iodothyronamine (3-T1AM), a signaling molecule with structural similarities to thyroid hormones, induces numerous physiological responses including reversible body temperature decline. One target of 3-T1AM is the trace amine-associated receptor 1 (TAAR1), which is a member of the rhodopsin-like family of G protein-coupled receptors (GPCRs). Interestingly, the effects of 3-T1AM remain detectable in TAAR1 knockout mice, suggesting further targets for 3-T1AM such as adrenergic receptors. Therefore, we evaluated whether β-adrenergic receptor 1 (ADRB1) and 2 (ADRB2) signaling is affected by 3-T1AM in HEK293 cells and in human conjunctival epithelial cells (IOBA-NHC), where these receptors are highly expressed endogenously. Methods: A label-free EPIC system for prescreening the 3-T1AM-induced effects on ADRB1 and ADRB2 in transfected HEK293 cells was used. In addition, ADRB1 and ADRB2 activation was analyzed using a cyclic AMP assay and a MAPK reporter gene assay. Finally, fluorescence Ca2+ imaging was utilized to delineate 3-T1AM-induced Ca2+ signaling. Results: 3-T1AM (10-5- 10-10M) enhanced isoprenaline-induced ADRB2-mediated Gs signaling but not that of ADRB1-mediated signaling. MAPK signaling remained unaffected for both receptors. In IOBA-NHC cells, norepinephrine-induced Ca2+ influxes were blocked by the nonselective ADRB blocker timolol (10 µM), indicating that ADRBs are most likely linked with Ca2+ channels. Notably, timolol was also found to block 3-T1AM (10-5M)-induced Ca2+ influx. Conclusions: The presented data support that 3-T1AM directly modulates β-adrenergic receptor signaling. The relationship between 3-T1AM and β-adrenergic signaling also reveals a potential therapeutic value for suppressing Ca2+ channel-mediated inflammation processes, occurring in eye diseases such as conjunctivitis.
4
Ghelardoni, Sandra, Grazia Chiellini, Sabina Frascarelli, Alessandro Saba, and Riccardo Zucchi. "Uptake and metabolic effects of 3-iodothyronamine in hepatocytes." Journal of Endocrinology 221, no. 1 (April 2014): 101–10. http://dx.doi.org/10.1530/joe-13-0311.
Повний текст джерелаАнотація:
3-Iodothyronamine (T1AM) is an endogenous relative of thyroid hormone with profound metabolic effects. In different experimental models, T1AM increased blood glucose, and it is not clear whether this effect is entirely accounted by changes in insulin and/or glucagone secretion. Thus, in the present work, we investigated the uptake of T1AM by hepatocytes, which was compared with the uptake of thyroid hormones, and the effects of T1AM on hepatic glucose and ketone body production. Two different experimental models were used: HepG2 cells and perfused rat liver. Thyronines and thyronamines (T0AMs) were significantly taken up by hepatocytes. In HepG2 cells exposed to 1 μM T1AM, at the steady state, the cellular concentration of T1AM exceeded the medium concentration by six- to eightfold. Similar accumulation occurred with 3,5,3′-triiodothyronine and thyroxine. Liver experiments confirmed significant T1AM uptake. T1AM was partly catabolized and the major catabolites were 3-iodothyroacetic acid (TA1) (in HepG2 cells) and T0AM (in liver). In both preparations, infusion with 1 μM T1AM produced a significant increase in glucose production, if adequate gluconeogenetic substrates were provided. This effect was dampened at higher concentration (10 μM) or in the presence of the amine oxidase inhibitor iproniazid, while TA1 was ineffective, suggesting that T1AM may have a direct gluconeogenetic effect. Ketone body release was significantly increased in liver, while variable results were obtained in HepG2 cells incubated with gluconeogenetic substrates. These findings are consistent with the stimulation of fatty acid catabolism, and a shift of pyruvate toward gluconeogenesis. Notably, these effects are independent from hormonal changes and might have physiological and pathophysiological importance.
5
Dinter, Juliane, Jessica Mühlhaus, Simon Friedrich Jacobi, Carolin Leonie Wienchol, Maxi Cöster, Jaroslawna Meister, Carolin Stephanie Hoefig та ін. "3-iodothyronamine differentially modulates α-2A-adrenergic receptor-mediated signaling". Journal of Molecular Endocrinology 54, № 3 (червень 2015): 205–16. http://dx.doi.org/10.1530/jme-15-0003.
Повний текст джерелаАнотація:
Mostin vivoeffects of 3-iodothyronamine (3-T1AM) have been thus far thought to be mediated by binding at the trace amine-associated receptor 1 (TAAR1). Inconsistently, the 3-T1AM-induced hypothermic effect still persists inTaar1knockout mice, which suggests additional receptor targets. In support of this general assumption, it has previously been reported that 3-T1AM also binds to the α-2A-adrenergic receptor (ADRA2A), which modulates insulin secretion. However, the mechanism of this effect remains unclear. We tested two different scenarios that may explain the effect: the sole action of 3-T1AM at ADRA2A and a combined action of 3-T1AM at ADRA2A and TAAR1, which is also expressed in pancreatic islets. We first investigated a potential general signaling modification using the label-free EPIC technology and then specified changes in signaling by cAMP inhibition and MAPKs (ERK1/2) determination. We found that 3-T1AM induced Gi/oactivation at ADRA2A and reduced the norepinephrine (NorEpi)-induced MAPK activation. Interestingly, in ADRA2A/TAAR1 hetero-oligomers, application of NorEpi resulted in uncoupling of the Gi/osignaling pathway, but it did not affect MAPK activation. However, 3-T1AM application in mice over a period of 6 days at a daily dose of 5 mg/kg had no significant effects on glucose homeostasis. In summary, we report an agonistic effect of 3-T1AM on the ADRA2A-mediated Gi/opathway but an antagonistic effect on MAPK induced by NorEpi. Moreover, in ADRA2A/TAAR1 hetero-oligomers, the capacity of NorEpi to stimulate Gi/osignaling is reduced by co-stimulation with 3-T1AM. The present study therefore points to a complex spectrum of signaling modification mediated by 3-T1AM at different G protein-coupled receptors.
6
Haiyan, Zhou, Hu Bailong, Zhang Bei, Wang Yiming, and Liu Xingde. "Comparative Transcriptome Analysis Reveals the Potential Cardiovascular Protective Targets of the Thyroid Hormone Metabolite 3-Iodothyronamine (3-T1AM)." BioMed Research International 2020 (June 20, 2020): 1–10. http://dx.doi.org/10.1155/2020/1302453.
Повний текст джерелаАнотація:
Background. The thyroid hormone metabolite 3-iodothyronamine (3-T1AM) is rapidly emerging as a promising compound in decreasing the heart rate and lowering the cardiac output. The aim of our study was to fully understand the molecular mechanism of 3-T1AM on cardiomyocytes and its potential targets in cardiovascular diseases. Materials and Methods. In our study, we utilized RNA-Seq to characterize the gene expression in H9C2 cells after 3-T1AM treatment. Comparative transcriptome analysis, including gene ontology, signaling pathways, disease connectivity analysis, and protein-protein interaction networks (PPI), was presented to find the critical gene function, hub genes, and related pathways. Results. A total of 1494 differently expressed genes (DEGs) were identified (192 upregulated and 1302 downregulated genes) in H9C2 cells for 3-T1AM treatment. Of these, 90 genes were associated with cardiovascular diseases. The PPI analysis indicated that 5 hub genes might be the targets of 3-T1AM. Subsequently, eight DEGs characterized using RNA-Seq were confirmed by RT-qPCR assays. Conclusions. Our study provides a comprehensive analysis of 3-T1AM on H9C2 cells and delineates a new insight into the therapeutic intervention of 3-T1AM for the cardiovascular diseases.
7
Cöster, Maxi, Heike Biebermann, Torsten Schöneberg, and Claudia Stäubert. "Evolutionary Conservation of 3-Iodothyronamine as an Agonist at the Trace Amine-Associated Receptor 1." European Thyroid Journal 4, Suppl. 1 (2015): 9–20. http://dx.doi.org/10.1159/000430839.
Повний текст джерелаАнотація:
Objectives: The trace amine-associated receptor 1 (Taar1) is a Gs protein-coupled receptor activated by trace amines, such as β-phenylethylamine (β-PEA) and 3-iodothyronamine (T1AM). T1AM is an endogenous biogenic amine and thyroid hormone derivative that exerts several biological functions. However, the physiological relevance of T1AM acting via Taar1 is still under discussion. Therefore, we studied the structural and functional evolution of Taar1 in vertebrates to provide evidence for a conserved Taar1-mediated T1AM function. Study Design: We searched public sequence databases to retrieve Taar1 sequence information from vertebrates. We cloned and functionally characterized Taar1 from selected vertebrate species using cAMP assays to determine the evolutionary conservation of T1AM action at Taar1. Results: We found intact open reading frames of Taar1 in more than 100 vertebrate species, including mammals, sauropsids and amphibians. Evolutionary conservation analyses of Taar1 protein sequences revealed a high variation in amino acid residues proposed to be involved in agonist binding, especially in rodent Taar1 orthologs. Functional characterization showed that T1AM, β-PEA and p-tyramine (p-Tyr) act as agonists at all tested orthologs, but EC50 values of T1AM at rat Taar1 differed significantly when compared to all other tested vertebrate Taar1. Conclusions: The high structural conservation of Taar1 throughout vertebrate evolution highlights the physiological relevance of Taar1, but species-specific differences in T1AM potency at Taar1 orthologs suggest a specialization of rat Taar1 for T1AM recognition. In contrast, β-PEA and p-Tyr potencies were rather conserved throughout all tested Taar1 orthologs. We provide evidence that the observed differences in potency are related to differences in constraint during Taar1 evolution.
8
Gencarelli, Manuela, Annunziatina Laurino, Elisa Landucci, Daniela Buonvicino, Costanza Mazzantini, Grazia Chiellini, and Laura Raimondi. "3-Iodothyronamine Affects Thermogenic Substrates’ Mobilization in Brown Adipocytes." Biology 9, no. 5 (May 4, 2020): 95. http://dx.doi.org/10.3390/biology9050095.
Повний текст джерелаАнотація:
We investigated the effect of 3-iodothyronamine (T1AM) on thermogenic substrates in brown adipocytes (BAs). BAs isolated from the stromal fraction of rat brown adipose tissue were exposed to an adipogenic medium containing insulin in the absence (M) or in the presence of 20 nM T1AM (M+T1AM) for 6 days. At the end of the treatment, the expression of p-PKA/PKA, p-AKT/AKT, p-AMPK/AMPK, p-CREB/CREB, p-P38/P38, type 1 and 3 beta adrenergic receptors (β1–β3AR), GLUT4, type 2 deiodinase (DIO2), and uncoupling protein 1 (UCP-1) were evaluated. The effects of cell conditioning with T1AM on fatty acid mobilization (basal and adrenergic-mediated), glucose uptake (basal and insulin-mediated), and ATP cell content were also analyzed in both cell populations. When compared to cells not exposed, M+T1AM cells showed increased p-PKA/PKA, p-AKT/AKT, p-CREB/CREB, p-P38/P38, and p-AMPK/AMPK, downregulation of DIO2 and β1AR, and upregulation of glycosylated β3AR, GLUT4, and adiponectin. At basal conditions, glycerol release was higher for M+T1AM cells than M cells, without any significant differences in basal glucose uptake. Notably, in M+T1AM cells, adrenergic agonists failed to activate PKA and lipolysis and to increase ATP level, but the glucose uptake in response to insulin exposure was more pronounced than in M cells. In conclusion, our results suggest that BAs conditioning with T1AM promote a catabolic condition promising to fight obesity and insulin resistance.
9
Galli, Elena, Maja Marchini, Alessandro Saba, Sergio Berti, Massimo Tonacchera, Paolo Vitti, Thomas S. Scanlan, Giorgio Iervasi, and Riccardo Zucchi. "Detection of 3-Iodothyronamine in Human Patients: A Preliminary Study." Journal of Clinical Endocrinology & Metabolism 97, no. 1 (January 1, 2012): E69—E74. http://dx.doi.org/10.1210/jc.2011-1115.
Повний текст джерелаАнотація:
Context and Objective: The primary purpose of this study was to detect and quantify 3-iodothyronamine (T1AM), an endogenous biogenic amine related to thyroid hormone, in human blood. Design: T1AM, total T3, and total T4 were assayed in serum by a novel HPLC tandem mass spectrometry assay, which has already been validated in animal investigations, and the results were related to standard clinical and laboratory variables. Setting and Patients: The series included one healthy volunteer, 24 patients admitted to a cardiological ward, and 17 ambulatory patients suspected of thyroid disease, who underwent blood sampling at admission for routine diagnostic purposes. Seven patients were affected by type 2 diabetes, and six patients showed echocardiographic evidence of impaired left ventricular function. Interventions: No intervention or any patient selection was performed. Main Outcome Measures: serum T1AM, total and free T3 and T4, routine chemistry, routine hematology, and echocardiographic parameters were measured. Results: T1AM was detected in all samples, and its concentration averaged 0.219 ± 0.012 pmol/ml. The T1AM concentration was significantly correlated to total T4 (r = 0.654, P < 0.001), total T3 (r = 0.705, P < 0.001), glycated hemoglobin (r = 0.508, P = 0.013), brain natriuretic peptide (r = 0.543, P = 0.016), and γ-glutamyl transpeptidase (r = 0.675, P < 0.001). In diabetic vs. nondiabetic patients T1AM concentration was significantly increased (0.232 ± 0.014 vs. 0.203 ± 0.006 pmol/ml, P = 0.044), whereas no significant difference was observed in patients with cardiac dysfunction. Conclusions: T1AM is an endogenous messenger that can be assayed in human blood. Our results are consistent with the hypothesis that circulating T1AM is produced from thyroid hormones and encourage further investigations on the potential role of T1AM in insulin resistance and heart failure.
10
Hackenmueller, Sarah A., Maja Marchini, Alessandro Saba, Riccardo Zucchi, and Thomas S. Scanlan. "Biosynthesis of 3-Iodothyronamine (T1AM) Is Dependent on the Sodium-Iodide Symporter and Thyroperoxidase but Does Not Involve Extrathyroidal Metabolism of T4." Endocrinology 153, no. 11 (November 1, 2012): 5659–67. http://dx.doi.org/10.1210/en.2012-1254.
Повний текст джерелаАнотація:
Abstract 3-Iodothyronamine (T1AM) is an endogenous thyroid hormone derivative with unknown biosynthetic origins. Structural similarities have led to the hypothesis that T1AM is an extrathyroidal metabolite of T4. This study uses an isotope-labeled T4 [heavy-T4 (H-T4)] that can be distinguished from endogenous T4 by mass spectrometry, which allows metabolites to be identified based on the presence of this unique isotope signature. Endogenous T1AM levels depend upon thyroid status and decrease upon induction of hypothyroidism. However, in hypothyroid mice replaced with H-T4, the isotope-labeled H-T3 metabolite is detected, but no isotope-labeled T1AM is detected. These data suggest that T1AM is not an extrathyroidal metabolite of T4, yet is produced by a process that requires the same biosynthetic factors necessary for T4 synthesis.
Дисертації з теми "T1AM"
1
Lorenzini, Leonardo. "Effects of T3 and 3-iodothyronamine (T1AM) on cellular metabolism, and influence of serum proteins on T1AM assay." Doctoral thesis, Università di Siena, 2018. http://hdl.handle.net/11365/1046523.
Повний текст джерелаАнотація:
Thyroxine (T4) is the predominant form of thyroid hormone (TH). In target tissues, T4 is enzymatically deiodinated to 3,5,3′-triiodothyronine (T3), a high-affinity ligand for the nuclear TH receptors TRα and Trβ. T3 modulates genes transcription via activation of TRα and TRβ. Non-genomic effects have also been described.
In 2004 the research groups of professors Scanlan Grandy and Zucchi discovered an endogenous thyroid hormone derivative called 3-iodothyronamine (T1AM). They proved that at nanomolar concentrations it can activate trace amine associated receptors 1 (TAARs)[1] and it may also interact with other targets, such as plasma membrane transporters, mitochondrial proteins and vesicular biogenic amine transporters [2]–[4]. Endogenous T1AM has been detected in human and rodent blood and tissues samples by liquid chromatography coupled mass spectrometry (LC/MS/MS) [5]. Its endogenous levels are a matter of argument due to the challenges that its accurate quantification poses. For this reason, so far a worldwide adopted extraction method has not been established. Circulating T1AM has so far been considered to be largely bound to apolipoprotein apoB100 [6].
The first T1AM functional effect to be discovered was severe hypothermia [7]. This effect is associated to a decrease in oxygen consumption and a reduction of the respiratory quotient (CO2/O2), which reflects the relationship between glucose and fatty acid oxidation, resulting in a shift from carbohydrate to lipid as energy source [8]. The molecular mechanisms underlying T1AM effects are still unknown, however Mariotti and colleagues [9] analyzed gene expression profiles in adipose tissue and liver of T1AM chronically treated rats and found significant transcriptional effects involving sirtuin genes, which regulate important metabolic pathways.
Therefore, the first aim of this work was to compare the effect of T1AM and T3 chronic treatment on mammalian sirtuin expression in hepatoma cells (HepG2) and isolated hepatocytes.
Isolated rat hepatocytes were obtained by liver in-situ collagenase perfusion. Sirtuin expression was determined by Western Blot analysis in cells treated for 24 h with 1-20 µM T1AM or T3. In addition, cell viability was evaluated by MTT test upon 24 h treatment with 100 nM to 20 µM T1AM or T3. In HepG2, T1AM significantly reduced SIRT1 and SIRT4 protein expression at 20 µM while T3 strongly decreased the expression of SIRT1 (20 µM) and SIRT2 (any tested concentration). In primary rat hepatocytes T1AM, did not affect protein expression whereas T3 decreased SIRT2 at 10 µM. The extent of MTT-staining was moderately but significantly reduced by T1AM, particularly in HepG2 cells, in which the effect occurred at concentration starting from 100 nM. T3 reduced MTT staining in HepG2 but not in isolated hepatocytes. T1AM and T3 differently affected sirtuin expression in hepatocytes. Since SIRT4 is an important regulator of lipid and glucose metabolism, whereas SIRT1 and SIRT2 have a key role in regulating cell cycle and tumorigenesis, our observations are consistent with the shift from carbohydrates to lipids induced by T1AM and indicate a potential new role of T1AM in modulating tumor proliferation.
The second part of this project was aimed at clarifying the issue that, so far, every research group working on this molecule has encountered when trying to accurately quantifying T1AM endogenous levels. These difficulties were usually attributed to problems in extraction or other pre‐analytical steps. Most researchers have developed various workaround for this issue. For example, on cell culture experiments, to avoid the presence of serum proteins in the culturing media, experiments have often be performed with unphysiological protein‐free media.
The second goal of this project was therefore to evaluate the effect of serum protein on the recovery of exogenous T1AM.
Cell culture media (Krebs buffer, DMEM, FBS, DMEM+FBS, used either in the absence or in the presence of NG108‐15 cells) and other biological matrices (rat brain and liver homogenates, human plasma and blood) were spiked with T1AM and/or deuterated T1AM (d4‐T1AM) and incubated for times ranging from 0 to 240 min. Samples were extracted using a liquid/liquid method and analysed using liquid chromatography coupled to mass spectrometry (LC-MS/MS), to assay T1AM and some of its metabolites. For the first time in the history of this molecule, in FBS‐containing buffers, an exponential decrease in T1AM levels was observed over time. T1AM metabolites were not detected, except for minimum amounts of TA1. Notably, d4‐T1AM decreased over time at a much lower rate, reaching 50‐70% of the baseline at 60 min. These effects were completely abolished by protein denaturation and partly reduced by semicarbazide, however, the process could not be reverted. In the presence of cells, T1AM concentration decreased virtually to 0 within 60 min, but TA1 accumulated in the incubation medium, with quantitative recovery. Spontaneous decrease in T1AM concentration with isotopic difference was confirmed in rat organ homogenates and human whole blood. Conclusions. On the whole, these results suggest binding and sequestration of T1AM by blood and tissue proteins, with significant isotope effects. These issues might account for the technical problems complicating the analytical assays of endogenousT1AM.
2
Lavinia, Bandini. "3-iodothyronamine (T1AM) effects on glutamatergic postsynaptic signaling pathway." Doctoral thesis, Università di Siena, 2022. http://hdl.handle.net/11365/1195192.
Повний текст джерелаАнотація:
Thyroid hormones (TH), namely thyroxine (T4) and 3,5,3’-triiodothyronine (T3), are crucial regulators of multiple growth processes and control systems of energy metabolism. T4 and T3 undergo a complex metabolism in vivo, by several enzymes encompassing deiodinases, amine transferases, amine oxidases, decarboxylases and several classes of conjugating enzymes, particularly sulfotransferases and UDP-glucuronosyltransferases.
T4 or T3 metabolites can produce significant functional effects when administered via interaction either with Thyroid Hormone Receptor (TR), or with other receptors. They are considered as chemical messengers further enriching TH signaling, and have become known as “novel thyroid hormones” or “active thyroid hormones metabolites”. These novel hormones include: T2; Thyronamines (TAMs), mostly 3-iodothyronamine (T1AM) and non-iodinated thyronamine (T0AM); thyroacetic acids, mostly 3,5,3’,5’-thyroacetic acid (TA4), 3,5,3’-thyroacetic acid (TA3), and 3-thyroacetic acid (TA1).
Recently, it emerged that 3-iodothyronamine (T1AM), a derivative of decarboxylation and deiodination of thyroid hormones, has pro-learning and anti-amnestic effects, modulates pain threshold, sleep pattern and food intake. It also counteracts beta-amyloid toxicity in mice.
Glutamatergic neurotransmission, the major excitatory system in the brain, plays a key role in regulating neuroplasticity, learning and memory, and it is often compromised in neurological disorders. T1AM reduced availability might results in some disorders associated with thyroid hormones. T1AM binds to the trace amine-associated receptor 1 (TAAR1) a G-protein coupled receptor with a putative role in neurotransmission.
In the present work, firstly we characterized the gene expression profile of two different brain cell lines and then we evaluated the effects of T1AM on the expression of proteins involved in the glutamatergic postsynaptic pathway.
A hybrid line of cancer cells of mouse neuroblastoma and rat glioma (NG 108-15) and a human glioblastoma cell line (U-87 MG) were used. We first characterized the in vitro model by analyzing gene expression of several proteins involved in the glutamatergic postsynaptic cascade by real time PCR (RT-PCR), and cellular uptake and metabolism of T1AM by HPLC coupled to mass spectrometry (HPLC MS-MS).
The cell lines were then treated with T1AM, ranging from 0.1 to 10 μM, alone or in combination with 10 µM resveratrol (RSV) and/or 10 µM amyloid β peptide (25-35). Cell viability, glucose consumption, protein expression, cAMP production and calcium concentration in cell lysates were assessed.
Our results indicated that both cell lines expressed receptors implicated in glutamatergic pathway, namely AMPA, NMDA and EphB2, but only U-87 MG cells expressed TAAR1 and they took up T1AM which was catabolized to TA1 and might be used as biochemical model to study its post synaptic signaling cascade.
At micromolar concentration T1AM had a slightly but significant cytotoxic effect, that is completely blunted if incubated with RSV and it was able to induce different post-translational modification in neuronal cell lines.
T1AM reduced glucose consumption and decreased intracellular calcium concentration in NG 108-15 cell line, while increased cAMP concentration, albeit at different doses.
At pharmacological concentrations, the major effect highlighted in both cell lines was an increase in the phosphorylation of proteins involved in the glutamatergic postsynaptic signaling.
In the NG 108-15 cells an increase in phosphorylation of ERK extracellular signal-regulated kinases (ERKs) (pERK/ total ERK) and CaMKII Ca-calmodulin-dependent protein kinase (CaMK) II (pCaMKII/total CaMKII).
In U-87 MG cells, T1AM induced the phosphorylation of the transcriptional factor cAMP response element-binding protein (CREB) and increase the expression of cFOS. Expression or post-translational modifications of other proteins were not affected.
We then extend investigation on the effects of 3-iodothyroacetic acid TA1, a catabolite of T1AM and of thyroid hormone, on brain cell lines focusing on the glutamatergic postsynaptic pathway that we explored by infusion with T1AM, assuming that TA1 may either strengthen T1AM effects or exert parallel actions, especially in brain tissue.
First, we assessed uptake and metabolism of TA1. Cell lines were treated with TA1 for 24h, at concentration ranging from 0.1 to 10 μM. Uptake, cell viability, cAMP production and protein expression were assessed.
TA1 was taken up by cells, even though only a slight reduction in medium concentration was recorded upon 24h of incubation. Cell viability was significantly increased by TA1 10 µM in U-87 MG cell line, while NG 108-15 cells were unaffected.
Western blot analysis indicated that, upon infusion of pharmacological doses of TA1, neither the expression of Sirtuin 1, (p=NS) nor the post-translational modifications of ERK (pERK/total ERK, p=NS) were affected in U-87 MG. Instead TA1 induced the phosphorylation of the transcriptional factor cAMP response element-binding protein (CREB) (pCREB/total).
In NG 108-15 cell line, preliminary analysis on protein expression and post-translational modification after TA1 infusion, indicated that no modifications of ERK (pERK/total ERK) were occurred.
In conclusion our results indicated that NG 108-15 and U-87 MG cells express receptors implicated in the glutamatergic system and, at pharmacological concentrations, T1AM can affect glutamatergic signaling.
Therefore, our preliminary results suggest that, in our experimental models, TA1 does not seem to mimic T1AM effects.
3
Sacripanti, Ginevra. "Thyroid hormone derivates T1AM and 3,5-T2: their effects on rat heart, NG108-15 and U-87 MG cell lines." Doctoral thesis, Università di Siena, 2020. http://hdl.handle.net/11365/1095534.
Повний текст джерелаАнотація:
The term “thyroid hormones”, classically referred to both 3,5,3′-triiodothyronine (T3) and thyroxine (T4), seems nowadays to be simplistic; some T3 and T4 metabolites, particularly 3,5diiodothyronine (3,5-T2) and 3-iodothyronamine (T1AM), are independent chemical messengers, with specific metabolic effects. In this PhD thesis we focused on the effects of these derivates on different tissues.
In the first project we evaluated the effects of T1AM on the glutamatergic pathway, the main excitatory system in brain. A cancer hybrid cell line of mouse neuroblastoma and rat glioma (NG108-15) and a human glioblastoma cell line (U-87 MG) were used as in vitro model and treated with different T1AM concentration for 24h, alone or in combination with resveratrol 10 µM and/or amyloid β peptide (25-35) 10 µM.
Firstly, we characterized cell lines for the expression of receptors implicated in glutamatergic pathway with real time PCR (qRT-PCR) and Western blot. Both cell lines expressed AMPA, NMDAR1 and EphB2, but only U-87 MG expressed TAAR1, the putative T1AM receptor. Using LC-MS-MS we discovered that both lines were able to take up T1AM and, rapidly catabolized it to TA1. In both cell lines, T1AM showed a slightly but significant cytotoxic action starting from 0.1 μM, that increase is presence of β-amyloid (10 µM), but not resveratrol (10 µM) evaluated by MTT test. We then evaluate glucose consumption using a glucose assay and observed in the NG108-15 a metabolic effect mediated by T1AM (p<0.05). For protein expression and post-translation modifications Western blot was used and an increase in the phosphorylation of Ca-calmodulin-dependent protein kinase (CaMK) II (pCaMKII/total CaKMII, p<0.05) in NG108-15 cell line was observed. In association with resveratrol T1AM could increase the expression of PKC (p<0.001 vs RSV) in the same cell line, a synergic effect showed exclusively in presence of both T1AM and resveratrol at all tested thyronamine concentration. In U-87 MG T1AM induce the phosphorylation of the transcriptional factor cAMP response element-binding protein (CREB) (PCREB/total CREB p<0.05).
Our results indicated that these two nervous cell lines express receptors implicated in glutamatergic system and might be used as biochemical model to study its post synaptic signaling cascade. T1AM had a minimal cytotoxic effect and it was able to induce different post-translational modification in neuronal cell lines. T1AM might activate mechanisms of action which included increasing CaMKII phosphorylation and PKC expression in NG108-15 while in U-87 MG induced the activation of the transcriptional factor CREB.
We then focused on another endogenous thyroid hormone derivate, the 3,5-diiodo-l-thyronine (3,5-T2) and its effect on heart which have been poorly investigated so far. It’s well understood that 3,5-T2 is able to regulate energy expenditure, resting metabolic rate and oxygen consumption with a mechanism that might involve mitochondria.
We decided to evaluate the functional metabolic, and toxic effect of 3,5-T2 using both in vitro and ex vivo models of cardiac preparations. As comparison for our results we also evaluated the response to T3 and T4. As cell culture we selected the H9c2 cells (rat cardiomyoblasts) to determine 3,5-T2, T3, and T4 uptake using LC-MS-MS. We treated cells with 3,5-T2 (0.1 to 10 µM) and evaluated cell viability using MTT test and crystal violet staining. We also investigate a possible 3,5-T2 metabolic effect performing a glucose and hexokinase assay. In the end we measured the cardiac functional effects, perfusing isolated working rat hearts with 3,5-T2, T3, or T4 in Krebs-Ringer buffer and recording hemodynamic variables.
H9c2 cells took up 3,5-T2, in cell lysate and the analyte levels increased slowly over time. 3,5-T2 significantly decreased MTT staining at 0.5–10 µM concentration, an effect confirmed by the crystal violet staining only at 10 µM T2, while equimolar T3 and T4 did not share this effect. In cells exposed to 0.1 or 1.0 µM of 3,5-T2 glucose uptake increased by 23% or 30% (p < 0.05). On the opposite side, T3 did not affect glucose consumption which was significantly reduced by 1 and 10 µM T4 (−24 and −41%, respectively, p < 0.01 and p < 0.0001). In the isolated perfused rat heart, 10 µM T2 produced a transient and slight reduction in the cardiac output and aortic flow (p<0.05), while thyroid hormone did not induce any hemodynamic change.
Our findings demonstrate that 3,5-T2 was taken up by cardiomyoblasts, and in a concentration range between 0.1 µM and 1.0 µM modulated cardiac energy metabolism increasing glucose accumulation. Furthermore, we observed some evidence of cytotoxicity and a transient impairment of contractile performance only at the highest 3,5-T2 concentration tested (10 µM). These effects seem to be specific for 3,5-T2, since they are not reproduced by thyroid hormone.
In the end we develop a novel ad-hoc optimized method to quantify T2 isomers using LC-MSMS in human serum.
T2 isomers (3,5-T2 and 3,3’-T2) has been detected in human blood using immunological methods, but until now a reliable assay based on mass spectrometry was not available. We obtained 2 mL of serum samples from 28 healthy subjects. The serum was firstly deproteinized with acetonitrile and then exposed to a solid phase extraction-based procedure. Then samples were furtherly cleaned by hexane washing and subjected to another step of deproteinization with acetonitrile to precipitate residual proteins. Both isomers were then analyzed by high performance liquid chromatography coupled to tandem mass spectrometry.
We developed a method with 88–104% accuracy, 95–97% precision, 78% recovery and a matrix effect average of +8%. In the serum sample 3,5-T2 was detected with a concentration averaged (mean ± SEM) 41 ± 5 pg/mL and 133±15 pg/mL for 3,3′-T2. Furthermore, we observed a significant correlation between 3,5-T2 and 3,3′-T2 concentrations (r = 0.540. p < 0.01), while no significant relation was observed with thyroid hormone.
In conclusion, this method can quantify both T2 isomers in human serum using a reliable assay based on LC-MS-MS. The concentrations of these isomers lie in the subnanomolar range and show a significant correlation in healthy subject.
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Rytkönen, M. (Mika). "Geographical study on childhood type 1 diabetes mellitus (T1DM) in Finland." Doctoral thesis, University of Oulu, 2004. http://urn.fi/urn:isbn:9514272862.
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Abstract
Type 1 diabetes mellitus (T1DM) among children is of a particular importance in Finland, where its incidence is the highest in the world and still increasing. However, the aetiology of T1DM is not fully known. According to current knowledge, both genetic and environmental factors operate together, leading to an attack by the immune system on the insulin-producing beta cells.
The purpose of this study was to investigate the geographical variation in the incidence of T1DM among children aged up to 14 years in Finland. Geographical Information Systems (GIS) and Bayesian spatial statistics were applied in a search for unusual spatial patterns and risk factor associations.
The incidence of T1DM among children aged up to 14 years showed clear geographical variations in Finland. Living in a rural environment increased the risk for T1DM, and the risk was particularly high among children living in rural heartland areas. There was no association between the variation in T1DM incidence and the zinc and nitrate concentrations of drinking water. A male excess in the incidence of T1DM was seen in the low-incidence areas. The geographical variation in the risk of T1DM was marked only among children aged up to 9 years.
Because genetics is a necessary but not a sufficient cause of T1DM, it could be hypothesized that there are some thus far unknown environmental risk factors affecting particularly younger children in Finland. Some of those factors may be related to a rural environment. The geographical variation in the M/F ratio of T1DM was a challenging observation and warrants more analytical study.
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Streeter, Leslie. "Feasibility of a School-Based Internet Intervention for Adolescents with T1DM." Thesis, The University of Arizona, 2014. http://hdl.handle.net/10150/322059.
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Rearick, Ellen M. "Parents of Children Newly Diagnosed with T1DM: Experiences with Social Support and Family Management: A Dissertation." eScholarship@UMMS, 2010. https://escholarship.umassmed.edu/gsn_diss/19.
Повний текст джерелаАнотація:
The purpose of this mixed-methods descriptive study with parents of children newly diagnosed with Type 1 diabetes was to explore their experiences with peer social support following the Social Support to Empower Parents (STEP) intervention and to examine the usefulness of the Family Management Measure (FaMM) in this population. The specific aims were to describe parents' experiences with the STEP social support intervention, describe parents' day-to-day diabetes management as measured by the FaMM, describe the relationship between parental management scores in the six FaMM dimensions and the social support intervention dose used, and explore FaMM scores in relationship to parent satisfaction with the STEP social support intervention. Identified themes of availability, practical tips, and common ground resonated throughout the interviews with parents and reflected Ireys' emotional, informational, and affirmational social support framework. Regardless of the intervention dose, number of parent mentor contacts, or scores on the FaMM scales, all parents interviewed when questioned, gave a 5/5 for satisfaction with the STEP RCT, qualitatively underscoring the positive effect of the intervention.
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Kinshuck, A. J. "A comparison of voice quality following radiotherapy or transoral laser microsurgery of T1a laryngeal carcinomas." Thesis, University of Liverpool, 2016. http://livrepository.liverpool.ac.uk/3004620/.
Повний текст джерелаАнотація:
Introduction: Patients with laryngeal carcinoma often present early due to the change in their voice. The treatment for T1aN0M0 carcinoma varies throughout the world, but whether radiotherapy (RT) or endolaryngeal laser excision is performed both result in excellent local control of the tumour and five year survival rates. There are advantages and disadvantages of either treatment but there are no appropriately powered randomised controlled trials comparing them. Over recent decades external beam RT has become the more popular choice and this is partly due to a perception of poor voice outcomes from surgical excision. However with the development of technology allowing surgical precision, transoral laser microsurgery (TLM) has resulted in low morbidity and good voice outcomes. Objective: This research has three main objectives: a. To describe acoustic parameters of ‘normal’ voice; b. To compare voice outcomes in patients treated with TLM with those treated with radiotherapy for T1a SCC of the glottis; c. To investigate longitudinal changes in voice quality in patients undergoing TLM for T1a SCC of the glottis. Methods: The research was divided into three main parts. The first part was to analyse the acoustic parameters of ‘normal’ voice. To describe the parameters of ‘normal’ voice, adults with no history of voice disorders who scored zero on the voice questionnaire (Voice Handicap Index - 10) were included. The second part comprised a comparative cohort study of 40 patients with T1aN0M0 laryngeal carcinoma, treated with either TLM (20 patients) or RT (20 patients) to compare voice outcomes at least one year following treatment. The third part involved a prospective cohort study of 30 patients with T1aN0M0 laryngeal carcinomas who were treated with TLM, comparing voice qualities before and after treatment. All patients were recruited from those attending the regional Head and Neck centre in Aintree University Hospital. The same methodology was adopted for voice recordings for all three parts of the study. Participants were asked to read a phonetically balanced passage and produce a prolonged vowel sound. In a sound proof room the voice recording included simultaneous audio and electrolaryngograph readings. The voice recordings were scored according to the GRBAS voice scale by an experienced rater. Acoustic analysis was performed form the electrolaryngograph recording using the SpeechStudioTM software. Several objective acoustic parameters were calculated from both sustained vowels and connected speech. These include: fundamental frequency (Fx), jitter, shimmer, harmonics to noise ratio (HNR) and normalized noise energy (NNE). In the comparative study of TLM versus RT and the prospective TLM study, patients were asked to complete voice-specific and quality of life questionnaires. The voice-specific questionnaires were the Voice Symptom Scale (VoiSS) and the Voice Handicap Index-10 (VHI-10). The quality of life questionnaire adopted was the University of Washington Quality of Life (UWQoL) version 4. Results: In the acoustic analysis of sustained vowels in normal speech, females have a statistically significantly higher Fx than males (adjusted p= < 0.05). There is no other statistically significant difference across the domains for sustained vowels in normal speech. In the analysis of connected speech, Fx is again higher in females (p < 0.001). There is no statistically significant difference in amplitude (Ax) or contact quotient (Qx). In the comparison of voice post TLM and RT, there is no statistical difference in voice-specific questionnaires between the groups. The UW-QoL4 found a statistically significantly higher QoL score in the TLM compared with the RT group for appearance (p=0.003), recreation (p=0.048), chewing (p=0.015) and saliva (p=0.016), however these are not statistically significant when adjusted for age. Overall for QoL, the RT group have a statistically significantly lower median score compared to TLM in physical function (p=0.004) and this remains statistically significant when adjusted for age (p=0.036). There is no statistically significant difference for social function (p=0.441). There is no statistically significant difference in perceptual rating (GRBAS score) between RT and TLM groups (total mean 5.49 vs. 5.12, p=0.254). Most domains as part of the acoustic analysis of sustained vowels show no statistically significant difference between RT and TLM. The mean Fx analysis on connective speech is statistically significantly higher in the TLM group (161.2Hz vs. 131.1Hz, adjusted p=0.001). Coherence of frequency is statistically significantly higher in the TLM group (48.6% vs. 36.0%, adjusted p=0.027) and pitch irregularity is statistically significantly higher in the RT group (26.7% vs. 14.9%, adjusted p=0.013). There is no statistically significant difference in mean amplitude between the two groups. Coherence of amplitude is statistically significantly higher in the TLM group (adjusted p=0.006) and amplitude irregularity is statistically significantly higher in the RT group, (12.4% vs. 6.3%, adjusted p=0.005). There is no statistically significant difference in mean contact quotient (p=0.368), coherence (p=0.236) or irregularity (p=0.125) when comparing TLM and RT. In the comparison of voice pre and post TLM, there is no statistical difference in voice-specific questionnaires between the groups. There is no statistically significant difference in the UW-QOLv4 domain scores or composite scores in patients pre- and post- TLM. There was no statistically significant difference in mean score for ‘G’,’R’,’B’ and ‘S’ indicators as part of perceptual rating between pre and post TLM patients, although asthenia was statistically significantly lower post-TLM (0.97 vs. 0.94, adjusted p=0.015). There is no statistically significant difference in any of the domains in the acoustic analysis of sustained vowels pre and post TLM. In the acoustic analysis of connected speech, the mean DFx is statistically significantly higher in the post TLM group (adjusted p=0.001). There is no statistically significant difference in the coherence of frequency or pitch irregularity when comparing pre and post TLM. There is no statistically significant difference in the mean DAx (p=0.121), coherence (p=0.472) or irregularity of amplitude (p=0.184) when comparing pre and post TLM. There is no statistically significant difference in the mean DQx (adjusted p=0.904), coherence (adjusted p=0.293) or irregularity of the contact quotient (adjusted p=0.400) when comparing pre and post TLM. Conclusion: The treatment of T1a laryngeal carcinoma with either TLM or RT has been shown to have comparably good local control. There are advantages and disadvantages of both treatments, however TLM is often preferred by patient and clinician as it is a day case procedure, can provide histological clearance and leaves the option to use RT in the future. However voice outcomes of the procedures have been debated with various reports in the literature. There are challenges when comparing the two treatment modalities due to a number of tumour, patient and surgical factors. It is not surprising that the voice is affected by whatever treatment is performed to treat the glottic carcinoma. This study shows that voice quality is good, however it is measured, for after both TLM and RT.
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Guo, Xiyuan [Verfasser]. "Immunhistochemische Untersuchung ausgewählter Oberflächenmarker zur Unterscheidung von Nierenzellkarzinomen im Stadium T1a und T1b / Xiyuan Guo." Lübeck : Zentrale Hochschulbibliothek Lübeck, 2017. http://d-nb.info/1143984994/34.
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Huestis, Samantha E. "Youth with Type 1 Diabetes Mellitus: An Investigation of the Role of Emotion Regulation as a Protective Factor for Depression and Anxiety." Case Western Reserve University School of Graduate Studies / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=case1275691384.
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Cousino, Melissa K. "The Role of Family Factors, Illness-Specific Youth Quality of Life and Pediatric Parenting Stress for Youth with Poorly Controlled Type 1 Diabetes." Case Western Reserve University School of Graduate Studies / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=case1315425765.
Повний текст джерелаКниги з теми "T1AM"
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Kh1ongh1ang h1ian thitsad1i kh1öng Sah1ai T1œngs1ieophing k1ieokap k1ank1ös1ang sangkhomniyom t1am s1isan kh1öng Chin: (1︢ekkas1an khonkhv1a). Vientiane: Khana S1inam khonkhv1a thitsad1i læ phuttikam k1öng Sunk1ang Phak, 1997.
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Ph1awa k1anphalit læ k1antal1at maid1ök maipradap: T1am khr1ongk1an phatthan1a tal1at ph1ưa sanapsanun k1ankra=ch1ai k1anphalit nai radap =changwat p1i ngoppram1an 2540. Sur1at Th1an1i: Samnakng1an Ph1anit =Changwat Sur1at Th1an1i, 1997.
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Butler, Gary, and Jeremy Kirk. Diabetes mellitus. Oxford University Press, 2011. http://dx.doi.org/10.1093/med/9780199232222.003.0042.
Повний текст джерелаАнотація:
Introduction to diabetes mellitus 116Type 1 diabetes (T1DM) 118Pathophysiology of type 1 diabetes 120Risks of developing type 1 diabetes 124Clinical features and development of type 1 diabetes 126Therapy of type 1 diabetes 128Insulins 130Diabetes monitoring 138Hypoglycaemia 142...
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Faddegon, Stephen, Ephrem O. Olweny, and Jeffrey A. Cadeddu. Ablative technologies for renal cancer. Edited by James W. F. Catto. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780199659579.003.0087.
Повний текст джерелаАнотація:
Nearly two-thirds of newly detected renal masses are clinical stage 1, with T1a tumours accounting for 60% of the newly detected stage 1 tumours. Guideline panels convened by the American Urological Association and the European Association of Urology recommend nephron-sparing surgery as the gold standard treatment for small renal masses, with active surveillance and thermal ablation recommended as alternative strategies in select patients. However, there is a dearth of studies directly comparing outcomes for energy-based ablation to those for traditional surgical treatments for small renal masses, and future prospective randomized trials will be invaluable in this regard. Ongoing research in renal tumour ablation targets several areas, including but not limited to achieving larger ablation sizes, decreasing morbidity, and development of novel technologies for renal tumour ablation.
Частини книг з теми "T1AM"
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Massana, Joaquim, Ferran Torrent-Fontbona, and Beatriz López. "Insulin Recommender Systems for T1DM: A Review." In Advances in Experimental Medicine and Biology, 331–55. Cham: Springer International Publishing, 2020. http://dx.doi.org/10.1007/5584_2020_482.
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Bracken, Richard M., Daniel J. West, and Stephen C. Bain. "Pre-exercise Insulin and Carbohydrate Strategies in the Exercising T1DM Individual." In Type 1 Diabetes, 47–71. London: Springer London, 2012. http://dx.doi.org/10.1007/978-0-85729-754-9_3.
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Phadke, Rekha, and H. C. Nagaraj. "Multivariate Long-Term Forecasting of T1DM: A Hybrid Econometric Model-Based Approach." In Emerging Research in Computing, Information, Communication and Applications, 1013–35. Singapore: Springer Nature Singapore, 2022. http://dx.doi.org/10.1007/978-981-19-5482-5_85.
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Weiss, Jeffrey N. "Stem Cell Mobilization (Plerixafor) and Immunologic Reset in Type 1 Diabetes (T1DM)." In Stem Cell Surgery Trials in Heart Failure and Diabetes, 125–29. Cham: Springer International Publishing, 2022. http://dx.doi.org/10.1007/978-3-030-78010-4_25.
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Reiterer, Florian, Phillipp Polterauer, Guido Freckmann, and Luigi del Re. "Identification of CGM Time Delays and Implications for BG Control in T1DM." In XIV Mediterranean Conference on Medical and Biological Engineering and Computing 2016, 190–95. Cham: Springer International Publishing, 2016. http://dx.doi.org/10.1007/978-3-319-32703-7_39.
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Goez-Mora, Jhon E., Monica Ayde Vallejo, and Pablo S. Rivadeneira. "Towards Event-Trigger Impulsive MPC for the Treatment of T1DM Handling Limited Resources." In Communications in Computer and Information Science, 180–89. Cham: Springer International Publishing, 2021. http://dx.doi.org/10.1007/978-3-030-86702-7_16.
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Lehocki, Fedor, and Tomas Bacigal. "Telemedicine and mHealth System for Complex Management in T1DM and T2DM Patients: Results of 6 Months Study." In XIV Mediterranean Conference on Medical and Biological Engineering and Computing 2016, 1131–36. Cham: Springer International Publishing, 2016. http://dx.doi.org/10.1007/978-3-319-32703-7_221.
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Choudhury, Shreyasi, Sonali Nashine, Yogesh Bhootada, Mansi Motiwale Kunte, Oleg Gorbatyuk, Alfred S. Lewin, and Marina Gorbatyuk. "Modulation of the Rate of Retinal Degeneration in T17M RHO Mice by Reprogramming the Unfolded Protein Response." In Retinal Degenerative Diseases, 455–62. New York, NY: Springer New York, 2014. http://dx.doi.org/10.1007/978-1-4614-3209-8_58.
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Wagner, David H. "The Search for Immunological Biomarkers in Type 1 Diabetes Mellitus (T1DM) and Multiple Sclerosis (MS): Th40 Cells Provide a Common Autoimmune Link." In Biomarkers in Diabetes, 575–96. Cham: Springer International Publishing, 2022. http://dx.doi.org/10.1007/978-3-031-08014-2_29.
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Wagner, David H. "The Search for Immunological Biomarkers in Type 1 Diabetes Mellitus (T1DM) and Multiple Sclerosis (MS): Th40 Cells Provide a Common Autoimmune Link." In Biomarkers in Diabetes, 1–23. Cham: Springer International Publishing, 2022. http://dx.doi.org/10.1007/978-3-030-81303-1_29-1.
Повний текст джерелаТези доповідей конференцій з теми "T1AM"
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Eigner, Gyorgy, Jozsef K. Tar, and Levente Kovacs. "Adaptive control solution for T1DM control." In 2015 IEEE 10th Jubilee International Symposium on Applied Computational Intelligence and Informatics (SACI). IEEE, 2015. http://dx.doi.org/10.1109/saci.2015.7208202.
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Prado, Vanildo, Daniel Buttros, Luciana Buttros de Paula, Benedito de Sousa Almeida Filho, Heloisa Maria de Luca Vespoli, Carla Kamya Pessoa, Eduardo Pessoa, and Eliana Aguiar Petri Nahás. "EVALUATION OF METABOLIC SYNDROME AND OBESITY IN BREAST CANCER SURVIVORS SUBJECTED TO INTERDISCIPLINARY APPROACH: A PROSPECTIVE COHORT STUDY." In Abstracts from the Brazilian Breast Cancer Symposium - BBCS 2021. Mastology, 2021. http://dx.doi.org/10.29289/259453942021v31s2081.
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Objective: The aim of this study was to assess the occurrence of metabolic syndrome (MetS), obesity, and abdominal obesity during the first year after a diagnosis of breast cancer. Methods: This prospective observational study included women with a recent diagnosis of breast cancer. Women aged ≥40 years, with a recent diagnosis of breast cancer, were included. The clinical, anthropometric, and biochemical analyses were performed. Women with three or more diagnostic criteria were considered with MetS as follows: waist circumference (WC) > 88 cm; triglycerides (TG) ≥150 mg/dL; high-density lipoprotein 30 kg/m2 and abdominal obesity with WC >88cm. The measurements were carried out in three moments: first medical assessment (T0m), six months (T6m), and 12 months later (T12m). All patients underwent the interdisciplinary assessment (i.e., nutritional and psychological) at T0m. For statistical analysis, the ANOVA with repeated measures and the chi-square test of trend were used. Results: A total of 72 women with breast cancer were included, with a mean age of 58.4±10.7 years. In the assessment of MetS, BMI, and WC, no difference was observed in the occurrence between the three moments. When comparing the individual metabolic syndrome criteria between the three moments, there was only a statistical difference in the TG and glycemia criteria. The analysis of blood glucose showed a decrease in mean values, with a value of 106.6 mg/dL-T0m, 100.46 mg/dL-T6m, and 98.96 mg/dL-T12m (p=0.004). Regarding TG, an increase in mean values was observed, with a value of 121 mg/dL-T0m, 139.4 mg/dL-T6m, and 148.46 mg/dL-T12m (p=0.003). No cancer treatment showed an impact on the measured criteria. Conclusion: The interdisciplinary approach on the breast cancer survivors demonstrated a positive impact on the control of metabolic syndrome, obesity, and abdominal obesity on the first year of follow-up. Additionally, glycemic indices showed a significant decrease, but an increase in TG values was observed.
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Rabbani, Naila, Alberto de a Fuente, and Paul Thornalley. "Risk prediction of early decline in renal function in diabetic kidney disease with algorithm including fractional excretion of glycated amino acids." In Qatar University Annual Research Forum & Exhibition. Qatar University Press, 2021. http://dx.doi.org/10.29117/quarfe.2021.0096.
Повний текст джерелаАнотація:
Background and aims: Diabetic kidney disease occurs in ca. 40% patients with diabetes. Approximately 1 in 5 patients with type 1 diabetes mellitus (T1DM) and 1 in 3 patients with type 2 diabetes mellitus (T2DM) develop early decline in renal function (EDRF), requiring renal dialysis after 5 - 20 years. Currently, at the time of normoalbuminuria or new onset microalbuminuria (incipient diabetic nephropathy), it is uncertain which patients are at risk of EDRF. With Joslin Kidney Study investigators, we found patients with T1DM who later developed EDRF (Decliners) have higher fractional excretion (FE) of 6 glycated amino acids - fructosyl-lysine and 5 advanced glycation endproducts (AGEs), compared to patients with stable renal function (Non-decliners). However, FE of any single glycated amino acid could not classify Decliners or Non-decliners. The aim of this study was to apply artificial intelligence machine learning to develop diagnostic algorithms to classify Decliners and Non-decliners by optimum combination of levels of glycated and oxidized amino acids in plasma and urine, related FEs and conventional clinical chemistry variables. Materials and methods: Patients with T1DM with stable renal function (n = 63) and EDRF (n = 22) were recruited for this study. Data on levels of 14 glycated and oxidized amino acids in plasma, urine, related FEs, glycated hemoglobin A1C, log(urinary albumin creatinine ratio, ACR), age, gender and duration of diabetes at the time of new onset microalbuminuria were included as features in algorithm development. Algorithms were trained and tested on 90%/10% data split, repeated 1000 times, using the Extreme Gradient Boosting method. Results: The algorithm gave an optimal classification of Decliners and Non-decliners. Optimum with features: A1C, log[ACR], FE(Nꞷ-carboxymethylarginine, CMA), FE(glyoxal-derived hydroimidazolone, G-H1) and plasma concentration of Nε-carboxymethyl-lysine (CML) free adduct; For The diagnostic performance for risk prediction of future EDRF was (mean ± SD): sensitivity 74 ± 9%, specificity 91 ± 45 and accuracy 87 ± 4%. The positive likelihood ratio LR+ was 11.0, indicating that this method gives strong, often conclusive evidence of future EDRF in patients with T1DM. In contrast, algorithms with A1C and logACR only as features gave LR+ 2.6, providing small evidence of risk of future EDRF. Conclusion: With conclude that FEs of glycated amino acids are novel risk predictors of EDRF, likely linked to reporting of early-decline of cationic amino acid transporter function in the renal tubular epithelium. Genetic polymorphism of these amino acid transporters has been linked to rapid decline in renal function in genome-wide association studies. Measurement of only 3 glycated amino acids, CMA, G-H1 and CML, produced an algorithm with optimum risk prediction of EDRF. With further validation, including in patients with T2DM and with chronic kidney disease without diabetes, this method may markedly improve clinical risk prediction of EDRF.
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Cescon, Marzia, and Eric Renard. "Adaptive subspace-based prediction of T1DM glycemia." In 2011 50th IEEE Conference on Decision and Control and European Control Conference (CDC-ECC 2011). IEEE, 2011. http://dx.doi.org/10.1109/cdc.2011.6161154.
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"T1A: Memory Circuits and Applications." In 2018 31st IEEE International System-on-Chip Conference (SOCC). IEEE, 2018. http://dx.doi.org/10.1109/socc.2018.8618575.
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"T1A: Power management and harvesting." In 2017 30th IEEE International System-on-Chip Conference (SOCC). IEEE, 2017. http://dx.doi.org/10.1109/socc.2017.8226041.
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Chan, Vinson Wai-Shun, Ahmad Abul, Filzah Osman, Helen Ng, Kaiwen Wang, Yuhong Yuan, Jon Cartledge, and Tze Min Wah. "Ablative Therapies versus Partial Nephrectomy for Small Renal Masses – A systematic review and meta-analysis of observational studies." In VIRTUAL ACADEMIC SURGERY CONFERENCE 2021. Cambridge Medicine Journal, 2021. http://dx.doi.org/10.7244/cmj.2021.04.001.3.
Повний текст джерелаАнотація:
Introduction: The ideal treatment of small renal masses is unclear. Ablative therapies (AT) have been considered as a potential alternative to partial nephrectomy (PN) due to their lower complication rates and similar oncological durability. We conducted a systematic review to compare oncological outcomes in T1a or T1b patients undergoing AT vs PN. Methods: This review is registered on PROSPERO (CRD42020199099). Medline, EMBASE, and Cochrane CENTRAL were searched to identify studies comparing AT and PN. The Cochrane RoB 2.0, ROBINS-I tool and the GRADE approach were used to assess any risk of biases. Results: From 1,748 identified records, 32 observational studies and 1 RCT involving 74,946 patients were included. AT patients were found to be significant older than PN patients (MD 5.70, 95% CI 3.83- 7.58), which highlights the serious confounding bias found in the included studies. Patients who received AT for T1a tumours were found to have significantly worse overall survival (HR 1.64, 95% CI 1.39-1.95), but similar cancer-specific survival (CSS), metastatic-free survival, and disease-free survival to PN. There were significantly fewer post-operative complications (RR 0.72, 95%CI 0.55- 0.94) and smaller decline in renal function post-operatively in AT (MD: -7.42, 95%CI -13.1- -1.70). In T1b patients, while CSS was similar between AT and PN, there is contradicting evidence for other oncological outcomes. Conclusion: AT is potentially non-inferior to PN in the treatment of T1a small renal masses due to similar long-term oncological durability, lower complication rates and better renal function preservation. In T1b patients, long-term high-quality studies are needed to confirm potential benefits of AT.
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Zahrani, Mina Mohammadi, Maryam Zekri, Soudabeh Taghian Dinani, and Marzieh Kamali. "MISO GPC for blood glucose control in T1DM." In 2016 24th Iranian Conference on Electrical Engineering (ICEE). IEEE, 2016. http://dx.doi.org/10.1109/iraniancee.2016.7585556.
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Cescon, Marzia, Rolf Johansson, and Eric Renard. "Low-complexity MISO models of T1DM glucose metabolism." In 2013 9th Asian Control Conference (ASCC). IEEE, 2013. http://dx.doi.org/10.1109/ascc.2013.6606387.
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Eigner, Gyorgy, Peter Pausits, and Levente Kovacs. "Control of T1DM via tensor product-based framework." In 2016 IEEE 17th International Symposium on Computational Intelligence and Informatics (CINTI). IEEE, 2016. http://dx.doi.org/10.1109/cinti.2016.7846379.
Повний текст джерелаЗвіти організацій з теми "T1AM"
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Ma, Huifen, Jiaxin Qiu, Peiju Mai, and Yijin Pei. Efficacy and safety of adult stem cell exosome transplantation for T1DM patients and animals: a meta-analysis. INPLASY - International Platform of Registered Systematic Review and Meta-analysis Protocols, January 2022. http://dx.doi.org/10.37766/inplasy2022.1.0006.
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Wang, Wanqing, Fei Huang, and Chunchao Han. Efficacy of Regimens in the Treatment of Latent Autoimmune Diabetes in Adults: A Network Meta-Analysis. INPLASY - International Platform of Registered Systematic Review and Meta-analysis Protocols, October 2022. http://dx.doi.org/10.37766/inplasy2022.10.0072.
Повний текст джерелаАнотація:
Review question / Objective: Efficacy of Regimens in the Treatment of Latent Autoimmune Diabetes in Adults: A Network Meta-Analysis. Condition being studied: Latent autoimmune diabetes mellitus (LADA) in adults is a highly heterogeneous autoimmune disease with clinical and genetic characteristics between Type 1 Diabetes（T1DM） and Type 2 Diabetes（T2DM）, and therefore there are no uniform criteria for the selection of therapeutic agents. We conducted a web-based meta analysis to evaluate the efficacy of various therapeutic agents for LADA by comparing their effects on various indicators reflecting LADA disease.