المؤلفون: Gennaro Ratti, Cinzia Monda, Federica Ratti, Marco Golino, Ludovica Fulgione, Cosimo Fulgione, Mario Mallardo, Paolo Tammaro

المصدر: Monaldi Archives for Chest Disease (2022)

مصطلحات موضوعية: Nuisance bleeding, dual antiplatelet therapy, quality of life, high ischemic risk, Medicine

الوصف: Long term dual antiplatelet therapy (LTDAPT), with ticagrelor 60 mg and low-dose aspirin, is indicated after acute coronary syndrome (ACS) for the secondary prevention of atherothrombotic events in high-risk patients with a history of ACS of at least 1 year. LTDAPT had a good tolerability and safety profile, but the risk of TIMI major bleeding was increased. However, even non-significant bleeding may be important because it has an effect on the quality of life and therefore may lead to treatment discontinuation. We, therefore, evaluated patients' experiences with LTDAPT and the impact of nuisance bleeding on quality of life and treatment adherence. We retrospectively reviewed 225 patients in follow-up after ACS with at least one high-risk condition, treated with ticagrelor 60 mg twice daily (after 90 mg twice daily for 12 months). The outpatient follow-up program after hospitalization provides a visit on day 30 after discharge, then after 3 months, continuing with six-monthly checks. We assessed the presence and intensity of bleeding, as well as health-related quality of life (HRQoL), at each visit. The TIMI score was used to determine the severity of the bleeding. Any overt bleeding event that did not meet the major and minor criteria was labeled "minimal" and could be framed as "nuisance bleeding." The HRQoL was assessed by the EuroQol-5 and Dimension (EQ-5D) visual analog scale (VAS) score. Minimal bleedings were present in 49 patients (21%), but only in one case (by decision of the patient) there was a cause for discontinuation of therapy. However, 39 (79%) subjects had asked for opinions on stopping the therapy during the telephone consultation. Factors influencing LTDAPT knowledge included access to medication counselling, engaging with information communicated during medication counselling, and access to timely, relevant and expert information and advice after discharge from the hospital. All adverse events, judged to be "not serious" in trials, may have an effect on the quality of life and therefore may lead to treatment discontinuation. The authors underline the importance of careful outpatient follow-up and ongoing counselling, to check out compliance and possible adverse effect of LTDAPT.

وصف الملف: electronic resource

العلاقة: https://www.monaldi-archives.org/index.php/macd/article/view/2437Test; https://doaj.org/toc/1122-0643Test; https://doaj.org/toc/2532-5264Test

الوصول الحر: https://doaj.org/article/d9b7d8954bc443c193ec160155b22291Test

المؤلفون: Nils Korte, Zeki Ilkan, Claire L. Pearson, Thomas Pfeiffer, Prabhav Singhal, Jason R. Rock, Huma Sethi, Dipender Gill, David Attwell, Paolo Tammaro

المصدر: The Journal of Clinical Investigation, Vol 132, Iss 9 (2022)

مصطلحات موضوعية: Cell biology, Vascular biology, Medicine

الوصف: Pericyte-mediated capillary constriction decreases cerebral blood flow in stroke after an occluded artery is unblocked. The determinants of pericyte tone are poorly understood. We show that a small rise in cytoplasmic Ca2+ concentration ([Ca2+]i) in pericytes activated chloride efflux through the Ca2+-gated anion channel TMEM16A, thus depolarizing the cell and opening voltage-gated calcium channels. This mechanism strongly amplified the pericyte [Ca2+]i rise and capillary constriction evoked by contractile agonists and ischemia. In a rodent stroke model, TMEM16A inhibition slowed the ischemia-evoked pericyte [Ca2+]i rise, capillary constriction, and pericyte death; reduced neutrophil stalling; and improved cerebrovascular reperfusion. Genetic analysis implicated altered TMEM16A expression in poor patient recovery from ischemic stroke. Thus, pericyte TMEM16A is a crucial regulator of cerebral capillary function and a potential therapeutic target for stroke and possibly other disorders of impaired microvascular flow, such as Alzheimer’s disease and vascular dementia.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1558-8238Test

الوصول الحر: https://doaj.org/article/3b8175d888bd4fc4971dd023142139a4Test

المؤلفون: Simon R. Bushell, Ashley C. W. Pike, Maria E. Falzone, Nils J. G. Rorsman, Chau M. Ta, Robin A. Corey, Thomas D. Newport, John C. Christianson, Lara F. Scofano, Chitra A. Shintre, Annamaria Tessitore, Amy Chu, Qinrui Wang, Leela Shrestha, Shubhashish M. M. Mukhopadhyay, James D. Love, Nicola A. Burgess-Brown, Rebecca Sitsapesan, Phillip J. Stansfeld, Juha T. Huiskonen, Paolo Tammaro, Alessio Accardi, Elisabeth P. Carpenter

المصدر: Nature Communications, Vol 10, Iss 1, Pp 1-16 (2019)

مصطلحات موضوعية: Science

الوصف: TMEM16K is a member of the TMEM16 family of integral membrane proteins that are either lipid scramblases or chloride channels. Here the authors combine cell biology, electrophysiology measurements, X-ray crystallography, cryo-EM and MD simulations to structurally characterize TMEM16K and show that it is an ER-resident lipid scramblase.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2041-1723Test

الوصول الحر: https://doaj.org/article/602dd2cc133c49529d8807b7b0d875caTest

المؤلفون: Gennaro Ratti, Antonio Maglione, Emilia Biglietto, Cinzia Monda, Ciro Elettrico, Federica Ratti, Cosimo Fulgione, Mario Mallardo, Paolo Tammaro

المصدر: Monaldi Archives for Chest Disease (2021)

مصطلحات موضوعية: Antiplatelet agents, dual antiplatelet therapy, high ischemic risk, percutaneous coronary intervention, Medicine

الوصف: Long term treatment with ticagrelor 60 mg and low-dose aspirin are indicated after acute coronary syndrome (ACS). We retrospectively reviewed aggregate data of 187 patients (155 M and 38 F) (mean age 63.8±9 years) in follow up after ACS with at least one high risk condition (Multivessel disease, diabetes, GFR65 years) treated with ticagrelor 60 mg twice daily (after 90 mg twice daily for 12 months). The results were compared with findings (characteristics of the patients at baseline, outcomes, bleeding) of PEGASUS-TIMI 54 trial and Eu Label. The highrisk groups were represented as follows: multivessel disease 105 pts (82%), diabetes 63 pts (33%), GFR< 60 mL/min 27 pts (14%), history of prior MI 33 pts (17%), >65 year aged 85 pts (45%). Treatment was withdrawn in 7 patients: 3 cases showed atrial fibrillation and were placed on oral anticoagulant drugs, one developed intracranial bleeding, in three patients a temporary withdrawal was due to surgery (1 colon polyposis and 2 cases of bladder papilloma). Chest pain without myocardial infarction occurred in 16 patients (revascularization was required in 9 patients). Dyspnea was present in 15 patients, but was not a cause for discontinuation of therapy. Long term treatment with ticagrelor 60 mg twice daily plus aspirin 100 mg/day showed a favourable benefit/risk profile after ACS. In this study all patients had been given ticagrelor 90 mg twice daily for 12 months and the 60 mg twice daily dosage was started immediately thereafter, unlike PEGASUS-TIMI 54 trial in which it was prescribed within a period ranging from 1 day to 1 year after discontinuation of the 90 mg dose. This makes our results more consistent with current clinical practice. However, a careful outpatient follow-up and constant counseling are mandatory to check out compliance to therapy and adverse side effects.

وصف الملف: electronic resource

العلاقة: https://www.monaldi-archives.org/index.php/macd/article/view/1881Test; https://doaj.org/toc/1122-0643Test; https://doaj.org/toc/2532-5264Test

الوصول الحر: https://doaj.org/article/2572885772c143f7bc3c7f30fff64d16Test

المؤلفون: Emilio Agostinelli, Paolo Tammaro

المصدر: International Journal of Molecular Sciences, Vol 23, Iss 3, p 1580 (2022)

مصطلحات موضوعية: Ca2+-activated Cl− channels, anoctamin, TMEM16x, scramblases, lipids, gating, Biology (General), QH301-705.5, Chemistry, QD1-999

الوصف: The TMEM16A/anoctamin-1 calcium-activated chloride channel (CaCC) contributes to a range of vital functions, such as the control of vascular tone and epithelial ion transport. The channel is a founding member of a family of 10 proteins (TMEM16x) with varied functions; some members (i.e., TMEM16A and TMEM16B) serve as CaCCs, while others are lipid scramblases, combine channel and scramblase function, or perform additional cellular roles. TMEM16x proteins are typically activated by agonist-induced Ca2+ release evoked by Gq-protein-coupled receptor (GqPCR) activation; thus, TMEM16x proteins link Ca2+-signalling with cell electrical activity and/or lipid transport. Recent studies demonstrate that a range of other cellular factors—including plasmalemmal lipids, pH, hypoxia, ATP and auxiliary proteins—also control the activity of the TMEM16A channel and its paralogues, suggesting that the TMEM16x proteins are effectively polymodal sensors of cellular homeostasis. Here, we review the molecular pathophysiology, structural biology, and mechanisms of regulation of TMEM16x proteins by multiple cellular factors.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/1422-0067/23/3/1580Test; https://doaj.org/toc/1661-6596Test; https://doaj.org/toc/1422-0067Test

الوصول الحر: https://doaj.org/article/e135a31271794f8f96cd81edc8082c5eTest

المؤلفون: Monica Lamberti, Gennaro Ratti, Donato Gerardi, Cristina Capogrosso, Gianfranco Ricciardi, Cosimo Fulgione, Salvatore Latte, Paolo Tammaro, Gregorio Covino, Albert Nienhaus, Elpidio Maria Garzillo, Mario Mallardo, Paolo Capogrosso

المصدر: International Journal of Occupational Medicine and Environmental Health, Vol 29, Iss 4, Pp 649-657 (2016)

مصطلحات موضوعية: depression, rehabilitation, workers, acute coronary syndrome, counseling, anxiety, Medicine

الوصف: Objectives: Coronary heart disease is frequent in the working-age population. Traditional outcomes, such as mortality and hospital readmission, are useful for evaluating prognosis. Fit-for-work is an emerging outcome with clinical as well as socioeconomic significance. We describe the possible benefit of a cardiac rehabilitation (CR) program for return to work (RTW) after acute coronary syndrome (ACS). Material and Methods: We evaluated 204 patients with recent ACS. They were divided into 4 groups on the basis of their occupational work load: very light (VL), light (L), moderate (M), and heavy (H). Work-related outcomes were assessed with the Work Performance Scale (WPS) of the Functional Status Questionnaire and as “days missed from work” (DMW) in the previous 4 weeks. The variables considered for outcomes were percent ejection fraction, functional capacity expressed in metabolic equivalents (METs), and participation or non-participation in the CR program (CR+ and CR–). Results: One hundred thirty (66%) patients took part in the CR program. Total WPS scores for CR+ and CR– subgroups were VL group: 18±4 vs. 14±4 (p < 0.001), L group: 18±3 vs. 14±3 (p < 0.0001), M group: 19±3 vs. 16±3 (p < 0.003), and H group: 20±4 vs. 17±3 (p < 0.006). Fewer DMW were reported by the CR+ group. Conclusions: Non-participation in CR was a consistent cause of poorer work-related outcomes. Our findings indicate that CR and occupational counseling play a very important role in worker recovery and subsequent reintegration in the workplace, in particular among clerical workers.

وصف الملف: electronic resource

العلاقة: http://ijomeh.eu/Work-related-outcome-after-acute-coronary-syndrome-Implications-of-complex-cardiac-nrehabilitation-in-occupational-medicine,58985,0,2.htmlTest; https://doaj.org/toc/1232-1087Test; https://doaj.org/toc/1896-494XTest

الوصول الحر: https://doaj.org/article/d55a3633beb14152b1a6bf0f05067b47Test

المؤلفون: Nellie Y Loh, Liz Bentley, Henrik Dimke, Sjoerd Verkaart, Paolo Tammaro, Caroline M Gorvin, Michael J Stechman, Bushra N Ahmad, Fadil M Hannan, Sian E Piret, Holly Evans, Ilaria Bellantuono, Tertius A Hough, William D Fraser, Joost G J Hoenderop, Frances M Ashcroft, Steve D M Brown, René J M Bindels, Roger D Cox, Rajesh V Thakker

المصدر: PLoS ONE, Vol 8, Iss 1, p e55412 (2013)

مصطلحات موضوعية: Medicine, Science

الوصف: Hypercalciuria is a major cause of nephrolithiasis, and is a common and complex disorder involving genetic and environmental factors. Identification of genetic factors for monogenic forms of hypercalciuria is hampered by the limited availability of large families, and to facilitate such studies, we screened for hypercalciuria in mice from an N-ethyl-N-nitrosourea mutagenesis programme. We identified a mouse with autosomal dominant hypercalciuria (HCALC1). Linkage studies mapped the Hcalc1 locus to a 11.94 Mb region on chromosome 6 containing the transient receptor potential cation channel, subfamily V, members 5 (Trpv5) and 6 (Trpv6) genes. DNA sequence analysis of coding regions, intron-exon boundaries and promoters of Trpv5 and Trpv6 identified a novel T to C transition in codon 682 of TRPV5, mutating a conserved serine to a proline (S682P). Compared to wild-type littermates, heterozygous (Trpv5(682P/+)) and homozygous (Trpv5(682P/682P)) mutant mice had hypercalciuria, polyuria, hyperphosphaturia and a more acidic urine, and ∼10% of males developed tubulointerstitial nephritis. Trpv5(682P/682P) mice also had normal plasma parathyroid hormone but increased 1,25-dihydroxyvitamin D(3) concentrations without increased bone resorption, consistent with a renal defect for the hypercalciuria. Expression of the S682P mutation in human embryonic kidney cells revealed that TRPV5-S682P-expressing cells had a lower baseline intracellular calcium concentration than wild-type TRPV5-expressing cells, suggesting an altered calcium permeability. Immunohistological studies revealed a selective decrease in TRPV5-expression from the renal distal convoluted tubules of Trpv5(682P/+) and Trpv5(682P/682P) mice consistent with a trafficking defect. In addition, Trpv5(682P/682P) mice had a reduction in renal expression of the intracellular calcium-binding protein, calbindin-D(28K), consistent with a specific defect in TRPV5-mediated renal calcium reabsorption. Thus, our findings indicate that the TRPV5 S682P mutant is functionally significant and study of HCALC1, a novel model for autosomal dominant hypercalciuria, may help further our understanding of renal calcium reabsorption and hypercalciuria.

وصف الملف: electronic resource

العلاقة: https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23383183/pdf/?tool=EBITest; https://doaj.org/toc/1932-6203Test

الوصول الحر: https://doaj.org/article/398083a269454e2e838e54531e91aaa4Test

المؤلفون: Fabrizio Oliva, Giuseppe Boriani, Paolo Calabrò, Pasquale Caldarola, Stefano Carugo, Battistina Castiglioni, Dario Celentani, Marco Comeglio, Leonardo De Luca, Renata De Maria, Michele Di Muro, Gianfranco Ignone, Filippo Leonardo, Alberto Margonato, Francesco Massari, Adriano Murrone, Federico Nardi, Giuseppe Patti, Gianpiero Perna, Paolo Pinna, Marco Poli, Francesco Prati, Riccardo Raddino, Sante Donato Pierdomenico, Paolo Tammaro, Italo Porto

المساهمون: Oliva, Fabrizio, Boriani, Giuseppe, Calabrò, Paolo, Caldarola, Pasquale, Carugo, Stefano, Castiglioni, Battistina, Celentani, Dario, Comeglio, Marco, De Luca, Leonardo, De Maria, Renata, Di Muro, Michele, Ignone, Gianfranco, Leonardo, Filippo, Margonato, Alberto, Massari, Francesco, Murrone, Adriano, Nardi, Federico, Patti, Giuseppe, Perna, Gianpiero, Pinna, Paolo, Poli, Marco, Prati, Francesco, Raddino, Riccardo, Pierdomenico, Sante Donato, Tammaro, Paolo, Porto, Italo

الوصف: Ischemia with non-obstructive coronary arteries (INOCA) is defined by the coexistence of anginal symptoms and demonstrable ischemia, with no evidence of obstructive coronary arteries. The underlying mechanism of INOCA is coronary microvascular dysfunction with or without associated vasospasm. INOCA patients have recurrent symptoms, functional limitations, repeated access to the emergency department, impaired quality of life and a higher incidence of cardiovascular events than the general population. Although well described in chronic coronary syndrome guidelines, INOCA remains underdiagnosed in clinical practice because of insufficient awareness, lack of accurate diagnostic tools, and poorly standardized and consistent definitions to diagnose, both invasively and non-invasively, coronary microvascular dysfunction.To disseminate current scientific evidence on INOCA as a distinct clinical entity, during 2022 we conducted at 30 cardiology units all over the country a clinical practice improvement initiative, with the aim of developing uniform and shared management pathways for INOCA patients across different operational settings. The present document highlights the outcomes of this multidisciplinary initiative.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/38639121; volume:25; issue:5; journal:GIORNALE ITALIANO DI CARDIOLOGIA; https://hdl.handle.net/11564/829572Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85191104862

الإتاحة: https://doi.org/10.1714/4252.42294Test
https://hdl.handle.net/11564/829572Test

المؤلفون: Rumaitha Al Hosni, Emilio Agostinelli, Zeki Ilkan, Lara F. Scofano, Kathryn Acheson, Andrew MacDonald, Dean Rivers, Martin Gunthorpe, Frances Platt, Paolo Tammaro

المصدر: Biophysical Journal. 122:458a

مصطلحات موضوعية: Biophysics

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::d8728cc1e0ed1560ff23e2446844da0cTest
https://doi.org/10.1016/j.bpj.2022.11.2463Test

المؤلفون: Rumaitha Al-Hosni, Zeki Ilkan, Emilio Agostinelli, Paolo Tammaro

المصدر: Trends in pharmacological sciences. 43(9)

مصطلحات موضوعية: Pharmacology, Cystic Fibrosis, Chloride Channels, Animals, Calcium, Toxicology, Anoctamin-1

الوصف: The TMEM16A Ca

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::084bacf7212bef8ae5fcb171beb8a524Test
https://pubmed.ncbi.nlm.nih.gov/35811176Test