Search results for "Transporter"
showing 6 items of 676 documents
Neonatal Respiratory Insufficiency Caused by an (Homozygous) ABCA3-Stop Mutation: a Systematic Evaluation of Therapeutic Options
2014
Background Autosomal recessive ABCA3 (ATP-binding cassette protein A3) gene mutations have been associated with neonatal respiratory distress and pediatric interstitial lung disease. The clinical course of the disease depends on the underlying mutations. Therefore, knowledge of course, symptoms and treatment of the disease is important. Patient and methods A term newborn suffered from progressive respiratory insufficiency, which led to death at the age of 4.8 months. The girl developed interstitial lung disease. Infections as well as structural and functional disorders of the lung were systematically excluded. A homozygous c.4681C > T (Arg 1561 Stop) mutation of the ABCA3 gene was identifie…
Polymorphisms in the Serotonin (5-Hydroxytryptamine (5-HT)) Type 2A Receptor (5-HTR2A) Gene, Other Related Genes and Anthropometry
2012
Serotonin or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter, which helps to regulate many physiological processes such as sleep, appetite, eating disorders, thermoregulation, hormone secretion, mood, anxiety, etc. The serotonin and related genes, such as the 5-HT2A receptor gene (HTR2A), the 5-HT transporter gene (SLC6A4), the 5-HT2C receptor gene (HTR2C), or the 5-HT1A receptor (HTR1A) gene, are re-emerging as powerful candidates for studying the association between food intake and anthropometry. Variations in all of these genes need to be studied to better understand the effects of serotonin and its receptors on anthropometry. The most widely studied polymorphism is the −1438G…
Role of hypoxia in pemetrexed-resistance of mesothelioma mediated by proton-coupled folate transporter, and preclinical activity of new anti-LDH comp…
2018
Introduction There are few effective therapies for malignant pleural mesothelioma (MPM), which remains one of the most lethal cancers. We previously demonstrated that low expression of the PCFT transporter, both at mRNA and protein levels, is associated with shorter survival of MPM patients treated with pemetrexed (Giovannetti et al., 2017). Since hypoxia has also been associated to antifolate-resistance (Raz et al, 2014), this study was aimed at elucidating key factors in pemetrexed resistance and hypoxia that may contribute to the rational development of novel therapeutic interventions against mesothelioma. Methods The levels of PCFT and of the hypoxia marker carbonic anhydrase-IX were de…
Rationale and design of the DARWIN-T2D (DApagliflozin Real World evIdeNce in Type 2 Diabetes): A multicenter retrospective nationwide Italian study a…
2017
Background Randomized controlled trials (RCTs) in the field of diabetes have limitations inherent to the fact that design, setting, and patient characteristics may be poorly transferrable to clinical practice. Thus, evidence from studies using routinely accumulated clinical data are increasingly valued. Aims We herein describe rationale and design of the DARWIN-T2D (DApagliflozin Real World evIdeNce in Type 2 Diabetes), a multicenter retrospective nationwide study conducted at 50 specialist outpatient clinics in Italy and promoted by the Italian Diabetes Society. Data synthesis The primary objective of the study is to describe the baseline clinical characteristics (particularly HbA1c) of pa…
Gitelman syndrome DD thiazide diuretics abuse
2014
Abstract Introduction. Gitelman syndrome (GS) is a rare inherited disorder. Mutations in SLC12A3 gene that encode tubular Na+Cl-cotransporter (NCCT) cause hypokalemic metabolic alkalosis, salt loss, hypomagnesaemia and hypocalciuria. The symptoms include weakness, vertigo, hypotension, tetany, paresthesia and nausea. Diagnostic criteria are a normal urine concentrating ability, normal glomerular filtration rate (GFR), hypomagnesaemia (<0,65mmol/l), hypokalemia (<3,6mmol/l) and hypocalciuria (<0,1mmol/mmol creatinine). Previously, the diagnosis was made by exclusion. Today, genetic analysis can ensure diagnosis. Thiazide diuretics (TD) abuse with similar abnormalities can make the d…
DESIGN OF SF3B1 SUBUNIT MODULATORS OF THE SF3B SPLICEOSOME COMPLEX
2022
The subject of this dissertation is the search for new therapeutic strategies for pancreatic cancer and aims to implement a Drug Discovery process for the rational design and synthesis of molecules active in the modulation of pathways related to the regulation of pre-mRNA splicing process. This research project is the result of a joint PhD between the University of Palermo, Italy, and the Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands. It integrates complementary skills in pharmaceutical chemistry and translational cancer research with a special focus on the rational design of new anticancer compounds potentially active on SF3B1 (Splicing Factor 3B …