196,112 research outputs found
Redox Properties of 3-Iodothyronamine (T1AM) and 3-Iodothyroacetic Acid (TA1)
No full text3-iodothyronamine (T1AM) and 3-iodothyroacetic acid (TA1) are thyroid-hormone-related compounds endowed with pharmacological activity through mechanisms that remain elusive. Some evidence suggests that they may have redox features. We assessed the chemical activity of T1AM and TA1 at pro-oxidant conditions. Further, in the cell model consisting of brown adipocytes (BAs) differentiated for 6 days in the absence (M cells) or in the presence of 20 nM T1AM (M + T1AM cells), characterized by pro-oxidant metabolism, or TA1 (M + TA1 cells), we investigated the expression/activity levels of pro-and anti-oxidant proteins, including UCP-1, sirtuin-1 (SIRT1), mitochondrial monoamine (MAO-A and MAO-B), semicarbazide-sensitive amine oxidase (SSAO), and reactive oxygen species (ROS)-dependent lipoperoxidation. T1AM and TA1 showed in-vitro antioxidant and superoxide scavenging properties, while only TA1 acted as a hydroxyl radical scavenger. M + T1AM cells showed higher lipoperoxidation levels and reduced SIRT1 expression and activity, similar MAO-A, but higher MAO-B activity in terms of M cells. Instead, the M + TA1 cells exhibited increased levels of SIRT1 protein and activity and significantly lower UCP-1, MAO-A, MAO-B, and SSAO in comparison with the M cells, and did not show signs of lipoperoxidation. Our results suggest that SIRT1 is the mediator of T1AM and TA1 pro-or anti-oxidant effects as a result of ROS intracellular levels, including the hydroxyl radical. Here, we provide evidence indicating that T1AM and TA1 administration impacts on the redox status of a biological system, a feature that indicates the novel mechanism of action of these two thyroid-hormone-related compounds
The 3-iodothyronamine (T1AM) and the 3-iodothyroacetic acid (TA1) indicate a novel connection with the histamine system for neuroprotection
No full textThe 3-iodothyronamine (T1AM) and 3-iodothryoacetic acid (TA1), are endogenous occurring compounds structurally related with thyroid hormones (THs, the pro-hormone T4 and the active hormone T3) initially proposed as possible mediators of the rapid effects of T3. However, after years from their identification, the physio-pathological meaning of T1AM and TA1 tissue levels remains an unsolved issue while pharmacological evidence indicates both compounds promote in rodents central and peripheral effects with mechanisms which remain mostly elusive. Pharmacodynamics of T1AM includes the recognition of G-coupled receptors, ion channels but also biotransformation into an active metabolite, i.e. the TA1. Furthermore, long term T1AM treatment associates with post-translational modifications of cell proteins. Such array of signaling may represent an added value, rather than a limit, equipping T1AM to play different functions depending on local expression of targets and enzymes involved in its biotransformation. Up to date, no information regarding TA1 mechanistic is available. We here review some of the main findings describing effects of T1AM (and TA1) which suggest these compounds interplay with the histaminergic system. These data reveal T1AM and TA1 are part of a network of signals involved in neuronal plasticity including neuroprotection and suggest T1AM and TA1 as lead compounds for a novel class of atypical psychoactive drugs. © 2021 Elsevier B.V.
3-Iodothyroacetic acid; 3-Iodothyronamine; Histamine; Neuroprotection; Thyroid hormone-related compounds; Thyroid hormone
Thyroid Hormone, Thyroid Hormone Metabolites and Mast Cells: A Less Explored Issue.
No full textMast cells are primary players in immune and inflammatory diseases. In the brain, mast cells are located at the brain side of the blood brain barrier (BBB) exerting a crucial role in protecting the brain from xenobiotic invasion. Furthermore, recent advances in neuroscience indicate mast cells may play an important role in glial cell-neuron communication through the release of mediators, including histamine. Interestingly, brain mast cells contain not only 50% of the brain histamine but also hormones, proteases and lipids or amine mediators; and cell degranulation may be triggered by different stimuli activating membrane bound receptors including the four types of histaminergic receptors. Among hormones, mast cells can store thyroid hormone (T3) and express membrane-bound thyroid stimulating hormone receptors (TSHRs), thus suggesting from one side that thyroid function may affect mast cells function, from the other that mast cell degranulation may impact on thyroid function. In this respect, the research on hormones in mast cells is scarce. Recent pharmacological evidence indicates the existence of a non-genomic portion of the thyroid secretion including thyroid hormone metabolites. Among which the 3,5 diiodothyronine (3,5-T2), 3-iodothyroanamine (T1AM) and 3-iodothyroacetic acid (TA1) are the most studied. All these compounds are endogenously occurring and found to be increased in inflammatory-based diseases involving mast cells. T1AM and TA1 induce, as T3, neuroprotective effects and itch but also hyperalgesia in rodents with a mechanism largely unknown but mediated by the release of histamine. Due to the rapid onset of their effectiveness they may trigger histamine release from a cell where it is "ready-to-be released," i.e., mast cells. Following a very thin path which passes through old experimental and clinical evidence, at the light of novel acquisitions on endogenous T3 metabolites, we aim to stimulate the attention on the possibility that mast cell histamine may be the connector of a novel (neuro) endocrine pathway linking the thyroid with mast cells
Brain histamine modulates the antidepressant-like effect of the 3-iodothyroacetic acid (TA1)
No full text3-iodothyroacetic acid (TA1), an end metabolite of thyroid hormone, has been shown to produce behavioral effects in mice that are dependent on brain histamine. We now aim to verify whether pharmacologically administered TA1 has brain bioavailability and is able to induce histamine-dependent antidepressant-like behaviors. TA1 brain, liver and plasma levels were measured by LC/MS-MS in male CD1 mice, sacrificed 15 min after receiving a high TA1 dose (330 μgkg-1). The hypothalamic mTOR/AKT/GSK-β cascade activation was evaluated in mice treated with 0.4, 1.32, 4 μgkg-1 TA1 by Western-blot. Mast cells were visualized by immuno-histochemistry in brain slices obtained from mice treated with 4 μgkg-1 TA1. Histamine release triggered by TA1 (20-1000 nM) was also evaluated in mouse peritoneal mast cells. After receiving TA1 (1.32, 4 or 11 μgkg-1; i.p.) CD1 male mice were subjected to the forced swim (FST) and the tail suspension tests (TST). Spontaneous locomotor and exploratory activities, motor incoordination, and anxiolytic or anxiogenic effects, were evaluated. Parallel behavioral tests were also carried out in mice that, prior to receiving TA1, were pre-treated with pyrilamine (10 μgkg-1I PYR) or zolantidine (5 μgkg-1; ZOL), histamine type 1 and type 2 receptor antagonists, respectively, or with p-chloro-phenylalanine (100 μgkg-1; PCPA), an inhibitor of serotonin synthesis. TA1 given i.p. to mice rapidly distributes in the brain, activates the hypothalamic mTOR/AKT and GSK-3β cascade and triggers mast cells degranulation. Furthermore, TA1 induces antidepressant effects and stimulates locomotion with a mechanism that appears to depend on the histaminergic system. TA1 antidepressant effect depends on brain histamine, thus highlighting a relationship between the immune system, brain inflammation and the thyroid. Copyright © 2019 Laurino, Landucci, Cinci, Gencarelli, De Siena, Bellusci, Chiellini and Raimondi
Ricerca dei campi di spostamento tra cartografia catastale e ortofoto: descrizione di una procedura e risultati di applicazioni a casi reali
No full textL’utilizzo delle ortofoto per l’individuazione di immobili che necessitano di aggiornamento catastale è recentemente diventata una tecnica diffusa. Il confronto tra cartografie e ortofoto ottenute con diverse proiezioni e diversamente referenziate è una delle principali problematiche da affrontare a tale scopo. Nell’articolo viene illustrato lo sviluppo di una procedura che utilizza l’individuazione automatica di punti omologhi, dopo una prima registration ed una selezione di interest points. Le prime applicazioni avevano evidenziato una serie di problematiche che sono state affrontate affidando ad un operatore l’accettazione dei risultati di correlazione automatica. La recente realizzazione della referenziazione delle mappe catastali d’impianto sulla CTR della Regione Calabria ha consentito di avere a disposizione una notevole mole di dati e di eseguire dei test per la validazione della procedura. Partendo dalle ortofoto della Regione Calabria e dai relativi fogli catastali già georeferenziati, sono stati eseguiti confronti affinando la registrazione geometrica mediante l’utilizzo automatico di corner detectors e cross correlation. I punti prescelti, dopo l’eliminazione di quelli con coefficiente di correlazione al di sotto di una soglia prefissata, sono sottoposti all’operatore, che è in grado di effettuare una valutazione immediata e di stabilire quelli affidabili e quelli da eliminare. La tecnica implementata consente così la determinazione dei campi di spostamento e, di conseguenza, la ricerca dei parametri di trasformazione in ogni zona delle ortofoto. Nell’articolo sono riportati i risultati dei test effettuat
3-iodothyronamine affects thermogenic substrates’ mobilization in brown adipocytes
No full textWe 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
Beach profile evolution and dune erosion due to the impact of hurricane Isabel
No full textThe present study analyzes the dune erosion and cross-shore beach profile evolution occurred in Outer Banks, North Carolina, in September 2003 during Hurricane Isabel. Several LIDAR (Light Detection And Ranging) profiles before (August 16, 2003) and after Isabel (September 21, 2003) are used to establish the dune erosion above the mean sea level. Twenty-nine survey profiles in the vicinity of the USACE Field Research Facility (FRF) at Duck, North Carolina, are examined to characterize the dune erosion and the cross-shore beach profile change in water depth less than 10 m and also to calibrate and verify the numerical model CSHORE. The model, based on the time-averaged continuity, cross-shore momentum, longshore momentum and energy equations, predicts the cross-shore variations of the free surface elevation, depth-averaged cross-shore and longshore fluid velocity as well as the suspended sand and bedload transport rates per unit of width
M-M36 Mitigates Risk Factors of Metabolic Syndrome and Promotes Visceral Fat Browning through β3-Adrenergic Receptor/UCP1 Signaling
No full textPre-metabolic syndrome (pre-MetS) may represent the best transition phase to start treatments aimed at reducing cardiometabolic risk factors of MetS. In this study, we investigated the effects of the marine microalga Tisochrysis lutea F&M-M36 (T. lutea) on cardiometabolic components of pre-MetS and its underlying mechanisms. Rats were fed a standard (5% fat) or a high-fat diet (20% fat) supplemented or not with 5% of T. lutea or fenofibrate (100 mg/Kg) for 3 months. Like fenofibrate, T. lutea decreased blood triglycerides (p < 0.01) and glucose levels (p < 0.01), increased fecal lipid excretion (p < 0.05) and adiponectin (p < 0.001) without affecting weight gain. Unlike fenofibrate, T. lutea did not increase liver weight and steatosis, reduced renal fat (p < 0.05), diastolic (p < 0.05) and mean arterial pressure (p < 0.05). In visceral adipose tissue (VAT), T. lutea, but not fenofibrate, increased the β3-adrenergic receptor (β3ADR) (p < 0.05) and Uncoupling protein 1 (UCP-1) (p < 0.001) while both induced glucagon-like peptide-1 receptor (GLP1R) protein expression (p < 0.001) and decreased interleukin (IL)-6 and IL-1β gene expression (p < 0.05). Pathway analysis on VAT whole-gene expression profiles showed that T. lutea up-regulated energy-metabolism-related genes and down-regulated inflammatory and autophagy pathways. The multitarget activity of T. lutea suggests that this microalga could be useful in mitigating risk factors of MetS
3-Iodothyronamine Affects Thermogenic Substrates' Mobilization in Brown Adipocytes.
No full textWe investigated the eect 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
(1–3AR), GLUT4, type 2 deiodinase (DIO2), and uncoupling protein 1 (UCP-1) were evaluated.
The eects 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 1AR,
and upregulation of glycosylated 3AR, GLUT4, and adiponectin. At basal conditions, glycerol
release was higher forM+T1AM cells thanMcells, without any significant dierences 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 resistanc
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