PMID- 24784951 OWN - NLM STAT- MEDLINE DCOM- 20150109 LR - 20151027 IS - 1879-0828 (Electronic) IS - 0953-6205 (Linking) VI - 25 IP - 5 DP - 2014 Jun TI - Statins decrease thrombin generation in patients with hypercholesterolemia. PG - 449-51 LID - 10.1016/j.ejim.2014.03.016 [doi] LID - S0953-6205(14)00091-0 [pii] AB - OBJECTIVE: Statins are cholesterol-lowering agents with antithrombotic effect possibly unrelated to their lipid-lowering properties. Traditional global coagulation tests failed, however, to reveal clinically relevant change after treatment. We therefore sought to investigate whether statins were able to modify thrombin generation in hypercholesterolemia. METHODS: Fifty-one patients who needed treatment with statins were enrolled in this study. Thrombin generation, assessed as endogenous thrombin potential (the amount of thrombin generated after triggering coagulation with small amount of tissue factor) was measured at pre- and two months post-treatment with statins. RESULTS: The median (inter-quartile range) level of total cholesterol that was 325 mg/dL (278-405) decreased significantly [211 mg/dL (197-247)] at post-treatment (p<0.001); the median level of HDL cholesterol that was 49 mg/dL (43-56) increased significantly [55 mg/dL (47-66)] at post-treatment (p<0.001). The median endogenous thrombin potential (inter-quartile range) before treatment was 2372 nM.min (2008-2617) and decreased to 2,048 nM.min (1764-2375) (p<0.001) after treatment. CONCLUSION: The results support the hypothesis of a direct link between statins and coagulation through their capacity to lower thrombin generation in patients with hypercholesterolemia. PRACTICE IMPLICATIONS: The antithrombotic properties of statins could be mediated (at least in part) by their endogenous thrombin potential lowering effect. This interesting hypothesis warrants evaluation by clinical trials. CI - Copyright (c) 2014. Published by Elsevier B.V. FAU - Tripodi, Armando AU - Tripodi A AD - Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Clinical Sciences and Community Health, Universita degli Studi di Milano, IRCCS Ca Granda Ospedale Maggiore Foundation, Milano, Italy. Electronic address: armando.tripodi@unimi.it. FAU - Pellegatta, Fabio AU - Pellegatta F AD - Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy; Department of Pharmacological Sciences and Biomolecular, University of Milan, Milan, Italy. FAU - Chantarangkul, Veena AU - Chantarangkul V AD - Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Clinical Sciences and Community Health, Universita degli Studi di Milano, IRCCS Ca Granda Ospedale Maggiore Foundation, Milano, Italy. FAU - Grigore, Liliana AU - Grigore L AD - Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy. FAU - Garlaschelli, Katia AU - Garlaschelli K AD - Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy. FAU - Baragetti, Andrea AU - Baragetti A AD - Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy; Department of Pharmacological Sciences and Biomolecular, University of Milan, Milan, Italy. FAU - Lemma, Laura AU - Lemma L AD - Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Clinical Sciences and Community Health, Universita degli Studi di Milano, IRCCS Ca Granda Ospedale Maggiore Foundation, Milano, Italy. FAU - Catapano, Alberico AU - Catapano A AD - Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy; Department of Pharmacological Sciences and Biomolecular, University of Milan, Milan, Italy; IRCCS Multimedica, Milano, Italy. LA - eng PT - Journal Article DEP - 20140429 PL - Netherlands TA - Eur J Intern Med JT - European journal of internal medicine JID - 9003220 RN - 0 (Cholesterol, HDL) RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) RN - EC 3.4.21.5 (Thrombin) SB - IM EIN - Eur J Intern Med. 2015 Jul;26(6):460 MH - Blood Coagulation/physiology MH - Cholesterol, HDL/blood MH - Humans MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*pharmacology MH - Hypercholesterolemia/*metabolism MH - Thrombin/*biosynthesis OTO - NOTNLM OT - Atherosclerosis OT - Endogenous thrombin potential OT - Hypercoagulability OT - Lipids OT - Thrombosis EDAT- 2014/05/03 06:00 MHDA- 2015/01/13 06:00 CRDT- 2014/05/03 06:00 PHST- 2013/12/16 00:00 [received] PHST- 2014/03/25 00:00 [revised] PHST- 2014/03/27 00:00 [accepted] PHST- 2014/05/03 06:00 [entrez] PHST- 2014/05/03 06:00 [pubmed] PHST- 2015/01/13 06:00 [medline] AID - S0953-6205(14)00091-0 [pii] AID - 10.1016/j.ejim.2014.03.016 [doi] PST - ppublish SO - Eur J Intern Med. 2014 Jun;25(5):449-51. doi: 10.1016/j.ejim.2014.03.016. Epub 2014 Apr 29. PMID- 24026546 OWN - NLM STAT- MEDLINE DCOM- 20150422 LR - 20181202 IS - 1935-5548 (Electronic) IS - 0149-5992 (Linking) VI - 37 IP - 1 DP - 2014 TI - Islet transplantation stabilizes hemostatic abnormalities and cerebral metabolism in individuals with type 1 diabetes. PG - 267-76 LID - 10.2337/dc13-1663 [doi] AB - OBJECTIVE Islets after kidney transplantation have been shown to positively affect the quality of life of individuals with type 1 diabetes (T1D) by reducing the burden of diabetes complications, but fewer data are available for islet transplantation alone (ITA). The aim of this study was to assess whether ITA has a positive impact on hemostatic and cerebral abnormalities in individuals with T1D. RESEARCH DESIGN AND METHODS Prothrombotic factors, platelet function/ultrastructure, and cerebral morphology, metabolism, and function have been investigated over a 15-month follow-up period using ELISA/electron microscopy and magnetic resonance imaging, nuclear magnetic resonance spectroscopy, and neuropsychological evaluation (Profile of Mood States test and paced auditory serial addition test) in 22 individuals with T1D who underwent ITA (n = 12) or remained on the waiting list (n = 10). Patients were homogeneous with regard to metabolic criteria, hemostatic parameters, and cerebral morphology/metabolism/function at the time of enrollment on the waiting list. RESULTS At the 15-month follow-up, the group undergoing ITA, but not individuals with T1D who remained on the waiting list, showed 1) improved glucose metabolism; 2) near-normal platelet activation and prothrombotic factor levels; 3) near-normal cerebral metabolism and function; and 4) a near-normal neuropsychological test. CONCLUSIONS ITA, despite immunosuppressive therapy, is associated with a near-normalization of hemostatic and cerebral abnormalities. FAU - D'Addio, Francesca AU - D'Addio F AD - Corresponding author: Paolo Fiorina, paolo.fiorina@childrens.harvard.edu. FAU - Maffi, Paola AU - Maffi P FAU - Vezzulli, Paolo AU - Vezzulli P FAU - Vergani, Andrea AU - Vergani A FAU - Mello, Alessandra AU - Mello A FAU - Bassi, Roberto AU - Bassi R FAU - Nano, Rita AU - Nano R FAU - Falautano, Monica AU - Falautano M FAU - Coppi, Elisabetta AU - Coppi E FAU - Finzi, Giovanna AU - Finzi G FAU - D'Angelo, Armando AU - D'Angelo A FAU - Fermo, Isabella AU - Fermo I FAU - Pellegatta, Fabio AU - Pellegatta F FAU - La Rosa, Stefano AU - La Rosa S FAU - Magnani, Giuseppe AU - Magnani G FAU - Piemonti, Lorenzo AU - Piemonti L FAU - Falini, Andrea AU - Falini A FAU - Folli, Franco AU - Folli F FAU - Secchi, Antonio AU - Secchi A FAU - Fiorina, Paolo AU - Fiorina P LA - eng GR - T32 DK007726/DK/NIDDK NIH HHS/United States GR - T32DK-007726-28/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20130911 PL - United States TA - Diabetes Care JT - Diabetes care JID - 7805975 RN - 0 (Blood Glucose) RN - 0 (Immunosuppressive Agents) SB - IM MH - Adult MH - Blood Glucose/metabolism MH - Blood Platelets/pathology/physiology MH - Brain/metabolism/pathology/*physiopathology MH - Diabetes Mellitus, Type 1/pathology/*physiopathology/psychology/*surgery MH - Female MH - *Hemostasis MH - Humans MH - Immunosuppressive Agents/therapeutic use MH - *Islets of Langerhans Transplantation MH - Male MH - Pilot Projects MH - Quality of Life MH - Retrospective Studies PMC - PMC3867995 EDAT- 2013/09/13 06:00 MHDA- 2015/04/23 06:00 CRDT- 2013/09/13 06:00 PHST- 2013/09/13 06:00 [entrez] PHST- 2013/09/13 06:00 [pubmed] PHST- 2015/04/23 06:00 [medline] AID - dc13-1663 [pii] AID - 10.2337/dc13-1663 [doi] PST - ppublish SO - Diabetes Care. 2014;37(1):267-76. doi: 10.2337/dc13-1663. Epub 2013 Sep 11. PMID- 16536881 OWN - NLM STAT- MEDLINE DCOM- 20060801 LR - 20181113 IS - 1471-2369 (Electronic) IS - 1471-2369 (Linking) VI - 7 DP - 2006 Mar 15 TI - Protective effect of EDTA preadministration on renal ischemia. PG - 5 AB - BACKGROUND: Chelation therapy with sodium edetate (EDTA) improved renal function and slowed the progression of renal insufficiency in patients subjected to lead intoxication. This study was performed to identify the underlying mechanism of the ability of EDTA treatment to protect kidneys from damage. METHODS: The effects of EDTA administration were studied in a rat model of acute renal failure induced by 60 minutes ischemia followed or not by 60 minutes reperfusion. Renal ischemic damage was evaluated by histological studies and by functional studies, namely serum creatinine and blood urea nitrogen levels. Treatment with EDTA was performed 30 minutes before the induction of ischemia. Polymorphonuclear cell (PMN) adhesion capability, plasmatic nitric oxide (NO) levels and endothelial NO synthase (eNOS) renal expression were studied as well as the EDTA protection from the TNFalpha-induced vascular leakage in the kidneys. Data was compared by two-way analysis of variance followed by a post hoc test. RESULTS: EDTA administration resulted in the preservation of both functional and histological parameters of rat kidneys. PMN obtained from peripheral blood of EDTA-treated ischemized rats, displayed a significant reduction in the expression of the adhesion molecule Mac-1 with respect to controls. NO was significantly increased by EDTA administration and eNOS expression was higher and more diffuse in kidneys of rats treated with EDTA than in the controls. Finally, EDTA administration was able to prevent in vivo the TNFalpha-induced vascular leakage in the kidneys. CONCLUSION: This data provides evidence that EDTA treatment is able to protect rat kidneys from ischemic damage possibly through the stimulation of NO production. FAU - Foglieni, Chiara AU - Foglieni C AD - Cardiovascular Department, Istituto Scientifico San Raffaele, via Olgettina, 60 Milan, Italy. foglieni.chiara@hsr.it FAU - Fulgenzi, Alessandro AU - Fulgenzi A FAU - Ticozzi, Paolo AU - Ticozzi P FAU - Pellegatta, Fabio AU - Pellegatta F FAU - Sciorati, Clara AU - Sciorati C FAU - Belloni, Daniela AU - Belloni D FAU - Ferrero, Elisabetta AU - Ferrero E FAU - Ferrero, Maria Elena AU - Ferrero ME LA - eng PT - Journal Article DEP - 20060315 PL - England TA - BMC Nephrol JT - BMC nephrology JID - 100967793 RN - 0 (Chelating Agents) RN - 0 (Macrophage-1 Antigen) RN - 0 (Tumor Necrosis Factor-alpha) RN - 31C4KY9ESH (Nitric Oxide) RN - 9G34HU7RV0 (Edetic Acid) RN - AYI8EX34EU (Creatinine) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type III) SB - IM MH - Acute Kidney Injury/drug therapy/physiopathology/prevention & control MH - Animals MH - Blood Urea Nitrogen MH - Capillary Permeability/drug effects/physiology MH - Cell Adhesion/physiology MH - Chelating Agents/*pharmacology/therapeutic use MH - Creatinine/blood MH - Disease Models, Animal MH - Disease Progression MH - Edetic Acid/*pharmacology/therapeutic use MH - Hemodynamics/drug effects/physiology MH - Ischemia/drug therapy/physiopathology/*prevention & control MH - Kidney/*blood supply/chemistry/*drug effects/pathology MH - Macrophage-1 Antigen/analysis MH - Male MH - Neutrophils/chemistry/pathology MH - Nitric Oxide/metabolism MH - Nitric Oxide Synthase Type III/analysis MH - Rats MH - Rats, Sprague-Dawley MH - Reperfusion Injury/drug therapy/physiopathology/prevention & control MH - Tumor Necrosis Factor-alpha/pharmacology PMC - PMC1501003 EDAT- 2006/03/16 09:00 MHDA- 2006/08/02 09:00 CRDT- 2006/03/16 09:00 PHST- 2005/11/22 00:00 [received] PHST- 2006/03/15 00:00 [accepted] PHST- 2006/03/16 09:00 [pubmed] PHST- 2006/08/02 09:00 [medline] PHST- 2006/03/16 09:00 [entrez] AID - 1471-2369-7-5 [pii] AID - 10.1186/1471-2369-7-5 [doi] PST - epublish SO - BMC Nephrol. 2006 Mar 15;7:5. doi: 10.1186/1471-2369-7-5. PMID- 15722404 OWN - NLM STAT- MEDLINE DCOM- 20050714 LR - 20180712 IS - 0022-3565 (Print) IS - 0022-3565 (Linking) VI - 313 IP - 3 DP - 2005 Jun TI - The acute estrogenic dilation of rat aorta is mediated solely by selective estrogen receptor-alpha agonists and is abolished by estrogen deprivation. PG - 1203-8 AB - Estrogen is known to induce rapid vasodilatory response in isolated arteries. Because estrogen is a nonselective receptor agonist, the involvement of estrogen receptor (ER) subtypes in acute estrogenic responses has remained elusive. Acute administration of the selective ERalpha agonist 4,4',4''-(4-propyl-[(1)H]pyrazole-1,3,5-triyl) tris-phenol (PPT) to precontracted aortic rings from intact female rats dose-dependently induced an ER-dependent vascular relaxation fully overlapping to that induced by 17beta-estradiol. By contrast, the selective ERbeta agonist 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN) had no acute effect on vasomotion. This short-term vasorelaxant action of PPT was abolished by the NO synthase inhibitor N(omega)-nitro-l-arginine methyl ester and by endothelium removal. In aortic tissues from ovariectomized (OVX) rats, however, neither 17beta-estradiol nor PPT induced acute vascular relaxation. The effect of PPT was restored in preparations from estrogen-replaced OVX rats, whereas DPN remained ineffective even after estrogen replacement. PPT acted through an ER-dependent mechanism, as shown by impaired response in the presence of the anti-estrogen ICI 182,780 (7alpha,17beta-[9[(4,4,5,5,5-pentafluoropentyl)sulfinyl]nonyl]estra-1,3,5(10)-tri ene-3,17-diol). Accordingly, isolated rat aortic endothelial cells expressed both ERalpha and ERbeta. These data show that selective ERalpha but not ERbeta agonists reproduced the acute vasodilation of estrogen via a receptor-mediated pathway in the aorta from intact as well as 17beta-estradiol-replaced OVX rats. This beneficial effect was undetectable in tissues from OVX rats. Selective pharmacological targeting of ER subtypes may thus represent a novel and promising approach in the treatment of vascular disease. FAU - Bolego, Chiara AU - Bolego C AD - Department of Pharmacological Sciences, University of Milan, Italy. FAU - Cignarella, Andrea AU - Cignarella A FAU - Sanvito, Paola AU - Sanvito P FAU - Pelosi, Valeria AU - Pelosi V FAU - Pellegatta, Fabio AU - Pellegatta F FAU - Puglisi, Lina AU - Puglisi L FAU - Pinna, Christian AU - Pinna C LA - eng PT - Journal Article DEP - 20050218 PL - United States TA - J Pharmacol Exp Ther JT - The Journal of pharmacology and experimental therapeutics JID - 0376362 RN - 0 (Estrogen Receptor alpha) RN - 0 (Phenols) RN - 0 (Pyrazoles) RN - 0 (Selective Estrogen Receptor Modulators) RN - 0T83Y6JZPF (4,4',4''-(4-propyl-((1)H)-pyrazole-1,3,5-triyl) tris-phenol) RN - 4TI98Z838E (Estradiol) SB - IM MH - Animals MH - Aorta/*drug effects/physiology MH - Cells, Cultured MH - Dose-Response Relationship, Drug MH - Estradiol/*pharmacology MH - Estrogen Receptor alpha/*physiology MH - Female MH - Ovariectomy MH - Phenols MH - Pyrazoles/pharmacology MH - Rats MH - Rats, Sprague-Dawley MH - Selective Estrogen Receptor Modulators/*pharmacology MH - Vasodilation/*drug effects EDAT- 2005/02/22 09:00 MHDA- 2005/07/15 09:00 CRDT- 2005/02/22 09:00 PHST- 2005/02/22 09:00 [pubmed] PHST- 2005/07/15 09:00 [medline] PHST- 2005/02/22 09:00 [entrez] AID - jpet.104.082867 [pii] AID - 10.1124/jpet.104.082867 [doi] PST - ppublish SO - J Pharmacol Exp Ther. 2005 Jun;313(3):1203-8. doi: 10.1124/jpet.104.082867. Epub 2005 Feb 18. PMID- 15331538 OWN - NLM STAT- MEDLINE DCOM- 20041026 LR - 20131121 IS - 0012-1797 (Print) IS - 0012-1797 (Linking) VI - 53 IP - 9 DP - 2004 Sep TI - Normalization of multiple hemostatic abnormalities in uremic type 1 diabetic patients after kidney-pancreas transplantation. PG - 2291-300 AB - To evaluate the effects of kidney-pancreas transplantation on hemostatic abnormalities in uremic type 1 diabetic patients, we conducted a cross-sectional study involving 12 type 1 diabetic patients, 30 uremic type 1 diabetic patients, 27 uremic type 1 diabetic patients who had a kidney-pancreas transplant, 12 uremic type 1 diabetic patients who had a kidney-alone transplant, and 13 healthy control subjects. We evaluated platelet and clotting system. Platelets in the group of uremic type 1 diabetic patients were significantly larger than platelets in the other groups. Resting calcium levels were significantly higher in the uremic type 1 diabetic patients and uremic type 1 diabetic patients who had a kidney-alone transplant than in the type 1 diabetic patients who had a kidney-pancreas transplant and control subjects. CD41 expression was significantly reduced in platelets from the uremic type 1 diabetic patients compared with the other groups. Levels of hypercoagulability markers in the type 1 diabetic patients who had a kidney-pancreas transplant and, to a lesser extent, the uremic type 1 diabetic patients who had a kidney-alone transplant but not the uremic type 1 diabetic patients were similar to those of the control subjects. A reduction in natural anticoagulants was evident in the uremic type 1 diabetic patients, whereas near-normal values were observed in the type 1 diabetic patients who had a kidney-pancreas transplant and uremic type 1 diabetic patients who had a kidney-alone transplant. Hemostatic abnormalities were not observed in type 1 diabetic patients who had a kidney-pancreas transplant. This finding might explain the lower cardiovascular death rate observed in type 1 diabetic patients who had a kidney-pancreas transplant compared with uremic type 1 diabetic patients who had a kidney-alone transplant or uremic type 1 diabetic patients. FAU - Fiorina, Paolo AU - Fiorina P AD - Internal Medicine, San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milano, Italy. FAU - Folli, Franco AU - Folli F FAU - D'Angelo, Armando AU - D'Angelo A FAU - Finzi, Giovanna AU - Finzi G FAU - Pellegatta, Fabio AU - Pellegatta F FAU - Guzzi, Valeria AU - Guzzi V FAU - Fedeli, Carlo AU - Fedeli C FAU - Della Valle, Patrizia AU - Della Valle P FAU - Usellini, Luciana AU - Usellini L FAU - Placidi, Claudia AU - Placidi C FAU - Bifari, Francesco AU - Bifari F FAU - Belloni, Daniela AU - Belloni D FAU - Ferrero, Elisabetta AU - Ferrero E FAU - Capella, Carlo AU - Capella C FAU - Secchi, Antonio AU - Secchi A LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Diabetes JT - Diabetes JID - 0372763 RN - 0 (Platelet Membrane Glycoprotein IIb) RN - 0 (Receptor, PAR-1) RN - 0 (Receptors, Thrombin) RN - 0 (protease-activated receptor 3) RN - SY7Q814VUP (Calcium) SB - AIM SB - IM MH - Adult MH - Blood Coagulation MH - Blood Coagulation Disorders/blood/*complications MH - Blood Platelets/metabolism MH - Calcium/metabolism MH - Cross-Sectional Studies MH - Diabetes Mellitus, Type 1/*blood/complications/surgery MH - Diabetic Nephropathies/blood/complications/surgery MH - Female MH - Humans MH - *Kidney Transplantation MH - Male MH - Middle Aged MH - *Pancreas Transplantation MH - Partial Thromboplastin Time MH - Platelet Membrane Glycoprotein IIb/metabolism MH - Prothrombin Time MH - Receptor, PAR-1/metabolism MH - Receptors, Thrombin/metabolism MH - Signal Transduction MH - Uremia/*blood/complications/surgery EDAT- 2004/08/28 05:00 MHDA- 2004/10/27 09:00 CRDT- 2004/08/28 05:00 PHST- 2004/08/28 05:00 [pubmed] PHST- 2004/10/27 09:00 [medline] PHST- 2004/08/28 05:00 [entrez] AID - 53/9/2291 [pii] PST - ppublish SO - Diabetes. 2004 Sep;53(9):2291-300. PMID- 12716675 OWN - NLM STAT- MEDLINE DCOM- 20030520 LR - 20181130 IS - 0002-9165 (Print) IS - 0002-9165 (Linking) VI - 77 IP - 5 DP - 2003 May TI - Different short- and long-term effects of resveratrol on nuclear factor-kappaB phosphorylation and nuclear appearance in human endothelial cells. PG - 1220-8 AB - BACKGROUND: Resveratrol (a naturally occurring phytoalexin found in grapes and wine) has cardiovascular protective effects that suggest the antiatherogenic (ie, antiinflammatory) activities of the compound on endothelial cells. OBJECTIVE: The antiinflammatory activity of resveratrol could be mediated by its interference with nuclear factor-kappaB (NF-kappaB)-dependent transcription. Thus, we studied the in vitro influence of physiologic concentrations of resveratrol (