1,721,011 research outputs found
Rare Causes of Hypercalcemia
No full text: This article discusses rare causes of hypercalcemia. Hypercalcemia can rarely be associated with immobilization, genetic diseases in children such as Williams-Beuren syndrome, Hypophosphatasia, Jansen Metaphyseal Chondrodysplasia (JMC), cosmetic injection, milk-alkali syndrome (MAS), calcium sulfate beads administration, manganese intoxication, postacute kidney failure recovery, and Paget's disease
Novel thyroid hormones
No full textThe field of thyroid hormone signaling has grown more complex in recent years. In particular, it has been suggested that some thyroid hormone derivatives, tentatively named "novel thyroid hormones" or "active thyroid hormone metabolites", may act as independent chemical messengers. They include 3,5-diiodothyronine (T2), 3-iodothyronamine (T1AM), and several iodothyroacetic acids, i.e., 3,5,3',5'-thyroacetic acid (TA4), 3,5,3'-thyroacetic acid (TA3), and 3-thyroacetic acid (TA1). We summarize the present knowledge on these compounds, namely their biosynthetic pathways, endogenous levels, molecular targets, and the functional effects elicited in experimental preparations or intact animals after exogenous administration. Their physiological and pathophysiological role is discussed, and potential therapeutic applications are outlined. The requirements needed to qualify these substances as chemical messengers must still be validated, although promising evidence has been collected. At present, the best candidate to the role of independent chemical messenger appears to be T1AM, and its most interesting effects concern metabolism and brain function. The responses elicited in experimental animals have suggested potential therapeutic applications. TA3 has an established role in thyroid hormone resistance syndromes, and is under investigation in Allen-Herndon-Dudley syndrome. Other potential targets are represented by obesity and dyslipidemia (for T2 and T1AM); dementia and degenerative brain disease (for T1AM and TA1); cancer (for T1AM and TA4). Another intriguing and unexplored question is the potential relevance of these metabolites in the clinical picture of hypothyroidism and in the response to replacement therapy
Vitamin D status and cardiovascular outcome
No full textIntroduction: Vitamin D is classically involved in maintaining bone and mineral health, but it has been shown to exert many extraskeletal functions, including pleiotropic effects on cardiovascular system. Materials and method: This review aims to summarize evidences in literature about vitamin D and cardiovascular outcome. Results and conclusions: Calcitriol or 1,25(OH)2D, the active hormone, binds to the specific nuclear receptor VDR, which is expressed in rat and human heart and vasculature and has effects on myocardiocytes, smooth cells, and endothelial cells. 25-Hydroxy-vitamin D (25OHD) represents the biomarker of vitamin D levels and reflects vitamin D status. There is consistent evidence that low serum 25OHD levels are associated with increased risk of cardiovascular diseases, including hypertension, coronary artery disease, ischemic heart disease, heart failure, stroke, and type 2 diabetes. Randomized-controlled trials and Mendelian randomization studies so far have not succeeded in proving a benefit of vitamin D supplementation. However, the latter investigations are affected by some methodological limitations, and therefore, it is still unclear if vitamin D deficiency has a causative role in cardiovascular diseases or is rather a marker of poor health in chronic disease
Transthyretin stabilization: An emerging strategy for the treatment of alzheimer’s disease?
Full text linkTransthyretin (TTR), previously named prealbumin is a plasma protein secreted mainly by the liver and choroid plexus (CP) that is a carrier for thyroid hormones (THs) and retinol (vitamin A). The structure of TTR, with four monomers rich in β-chains in a globular tetrameric protein, accounts for the predisposition of the protein to aggregate in fibrils, leading to a rare and severe disease, namely transthyretin amyloidosis (ATTR). Much effort has been made and still is required to find new therapeutic compounds that can stabilize TTR (“kinetic stabilization”) and prevent the amyloid genetic process. Moreover, TTR is an interesting therapeutic target for neurodegenerative diseases due to its recognized neuroprotective properties in the cognitive impairment context and interestingly in Alzheimer’s disease (AD). Much evidence has been collected regarding the neuroprotective effects in AD, including through in vitro and in vivo studies as well as a wide range of clinical series. Despite this supported hypothesis of neuroprotection for TTR, the mechanisms are still not completely clear. The aim of this review is to highlight the most relevant findings on the neuroprotective role of TTR, and to summarize the recent progress on the development of TTR tetramer stabilizers
A Dynamical Model of Electro-Injectors for Common Rail Diesel Engines
No full textResearch on Common Rail (CR) injection systems
has helped to increase the performance of Diesel engines in
terms of available power and fuel consumption in compliance
with the restrictions of noise and pollutant emissions. To
accomplish these tasks, the last generation of electro-injectors
is being developed to advance and improve structure and
operation in achieving an accurate fuel metering. This paper
presents a model of an electro-injector for common rail systems
that is able to predict steady-state and transient behavior.
Good results are obtained by simulation in different working
conditions and match experimental data to a good extent
Selective Thyroid Hormone Receptor-Beta (TRβ) Agonists: New Perspectives for the Treatment of Metabolic and Neurodegenerative Disorders
Full text linkThyroid hormones (THs) elicit significant effects on numerous physiological processes, such as growth, development, and metabolism. A lack of thyroid hormones is not compatible with normal health. Most THs effects are mediated by two different thyroid hormone receptor (TR) isoforms, namely TRα and TRβ, with the TRβ isoform known to be responsible for the main beneficial effects of TH on liver. In brain, despite the crucial role of TRα isoform in neuronal development, TRβ has been proposed to play a role in the remyelination processes. Consequently, over the past two decades, much effort has been applied in developing thyroid hormone analogs capable of uncoupling beneficial actions on liver (triglyceride and cholesterol lowering) and central nervous system (CNS) (oligodendrocyte proliferation) from deleterious effects on the heart, muscle and bone. Sobetirome (GC-1) and subsequently Eprotirome (KB2115) were the first examples of TRβ selective thyromimetics, with Sobetirome differing from the structure of thyronines because of the absence of halogens, biaryl ether oxygen, and amino-acidic side chain. Even though both thyromimetics showed encouraging actions against hypercholesterolemia, non-alcoholic steatohepatitis (NASH) and in the stimulation of hepatocytes proliferation, they were stopped after Phase 1 and Phase 2–3 clinical trials, respectively. In recent years, advances in molecular and structural biology have facilitated the design of new selective thyroid hormone mimetics that exhibit TR isoform-selective binding, and/or liver- and tissue-selective uptake, with Resmetirom (MGL-3196) and Hep-Direct prodrug VK2809 (MB07811) probably representing two of the most promising lipid lowering agents, currently under phase 2–3 clinical trials. More recently the application of a comprehensive panel of ADME-Toxicity assays enabled the selection of novel thyromimetic IS25 and its prodrug TG68, as very powerful lipid lowering agents both in vitro and in vivo. In addition to dyslipidemia and other liver pathologies, THs analogs could also be of value for the treatment of neurodegenerative diseases, such as multiple sclerosis (MS). Sob-AM2, a CNS- selective prodrug of Sobetirome has been shown to promote significant myelin repair in the brain and spinal cord of mouse demyelinating models and it is rapidly moving into clinical trials in humans. Taken together all these findings support the great potential of selective thyromimetics in targeting a large variety of human pathologies characterized by altered metabolism and/or cellular differentiation
Autogestione di sistemi di istruzione e performance di compiti funzionali in persone con ritardo mentale grave
No full textHPLC-MS-MS 25OHVITAMIND LEVELS ARE ASSOCIATED WITH PROGNOSIS MARKERS OF HEART FAILURE
No full textIntroduction and Aims: Heart failure (HF) is a health problem with poor prognosis, despite many treatments available. Vitamin D is the prehormone of the active calcitriol (1,25(OH)2D3). It is involved in bone homeostasis, but recent studies suggest extra skeletal functions, including pleiotropic effects on cardiovascular system and a relationship between low levels of 25OH-D and worse HF prognosis. The aims of the study were: 1) to define 25 OH-D levels in the HF population, 2) to correlate 25 OH-D levels and HF outcome markers (biochemical and instrumental evaluation) in the hypothesis vitamin D represents a potential “modifiable" factor risk in HF.
Materials and Methods: We performed a retrospective study on 261 consecutive HF patients (NHYA 1–3), collecting clinical, biochemical and instrumental data (echocardiography and cardiopulmonary exercise test–CPET). We retrieved stored blood samples collected at the baseline and developed a fast isotope dilution mass spectrometry coupled with liquid chromatography (HPLC-MS-MS) method for accurate measurement of 25OH-D levels.
Results: Patients were 47 females and 214 males (ratio M:F=4:1), with a mean age of 65±12 years and mean BMI of 28±14. They had stable HF disease in prevalent NYHA 2class. Mean EF (ejection fraction) was 33± 8 %; patients had mild kidney failure (creatinine 1.12 ± 0.3 mg/dl) and they were normocalcemic and normo-PTH. Levels of 25OHvitaminD ranged 2–45 ng/ml, with mean of 17 ± 9 ng/ml. 25 % (n=65)patients had vitamin D deficiency (<10 ng/ml), 62 % (n=161)had vitamin insufficiency (between 10–30 ng/ml) and 13 %(n= 35) had vitamin >30 ng/ml, without any supplementation. The linear regression analysis showed that 25OH-D levels were positively correlated with CPET parameters and negatively with mortality Mecki score and this relation was even stronger inpatient with vitamin D insufficiency.
Conclusion: Our study revealed a strong association between variables from CPET, a well recognized valuable tool for HF prognosis and 25OH-D levels, detected with a new and accurate method HPLC- MS-MS
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