31799254 2019 12 07

2296-858X 6 2019 Front Med (Lausanne) Copper/Zinc-Superoxide Dismutase in Human Epidermis: An Immunochemical Study. 258 10.3389/fmed.2019.00258 The localization of copper and zinc-superoxide dismutase in normal and neoplastic human skin was examined with immunochemical techniques. Skin samples were taken from males and females of different ages, UV exposed and non-exposed areas and basal-/spino-cellular carcinomas. The enzyme was localized diffusely in the cytoplasm and was also found in the nuclei of epidermal cells, endothelial cells and other dermis cell types. The dismutase content in the epidermis was higher in males than females, UV-exposed than non-exposed and young than old people. In the tumors, the enzyme content of the superficial epidermal layers was higher than in the deep tumoral epithelial cells. These data suggest that the localization of Cu, Zn-SOD in skin tissues reflects the gender and age of the subject, the cell types and their normal or diseased state. Further studies based on the investigation of systemic changes of this enzyme in physiological and pathological epidermis could provide additional information on tumor cell generation. Copyright © 2019 Altobelli, Van Noorden and Cimini. Altobelli Giovanna G GG Department of Advanced Biomedical Sciences, Medical School, Federico II University of Naples, Naples, Italy. Van Noorden Susan S Department of Histopathology, Imperial College London, Hammersmith Hospital, London, United Kingdom. Cimini Vincenzo V Department of Advanced Biomedical Sciences, Medical School, Federico II University of Naples, Naples, Italy. eng Journal Article 2019 11 13

Switzerland Front Med (Lausanne) 101648047 2296-858X Cu Zn-superoxide dismutase densitometry human skin immunochemistry skin tumors 2019 08 01 2019 10 25 2019 12 5 6 0 2019 12 5 6 0 2019 12 5 6 1 epublish 31799254 10.3389/fmed.2019.00258 PMC6874168 Nature. 1979 Apr 19;278(5706):737-8 431730 Biochemistry. 1975 Dec 2;14(24):5299-303 172122 J Invest Dermatol. 1994 Jan;102(1):122-4 8288904 J Biol Chem. 1982 May 25;257(10):5751-4 6279612 J Invest Dermatol. 2002 Apr;118(4):618-25 11918707 J Invest Dermatol. 2006 Dec;126(12):2565-75 17108903 J Invest Dermatol. 1999 Nov;113(5):843-7 10571743 J Histochem Cytochem. 2006 Jun;54(6):739-43 16399996 J Invest Dermatol. 2002 Sep;119(3):645-52 12230508 Histochem Cell Biol. 2002 Aug;118(2):163-9 12189519 J Invest Dermatol. 2003 Mar;120(3):434-9 12603857 Head Neck. 2002 Sep;24(9):859-67 12211050 Comp Biochem Physiol Biochem Mol Biol. 1994 Jul;108(3):309-13 8081657 Exp Dermatol. 1997 Jun;6(3):116-21 9226133 Mutat Res. 1999 Jan 25;423(1-2):11-21 10029667 Br J Dermatol. 1991 Jun;124(6):555-9 2064938 29682745 2019 09 30 2019 09 30

1097-4652 233 10 2018 10 J. Cell. Physiol. Calcium-binding protein and some neuropeptides in the retina of Octopus vulgaris: A morpho-histochemical study. 6866-6876 10.1002/jcp.26570 The existence of both calcium-binding proteins (CBPs) and neuropeptides in the retina and brain of various species of vertebrates and invertebrates is well documented. Octopus retina is particularly interesting because it represents a case of convergent evolution. The aim of this study was to characterize the distribution of two CBPs, calretinin and calbindin, in Octopus retina using morphology, in situ hybridization, immunocytochemistry and Western blot. Calretinin-like immunoreactivity was found in the photoreceptor cells, but unexpectedly also in the supporting cells. In situ hybridization and Western blot analysis confirmed these results. No immunoreactivity was found for calbindin. Two neuropeptides, Substance P and calcitonin gene-related peptide (CGRP), as well as neurofilament protein and glial fibrillary acidic protein were also localized in the Octopus retina by immunocytochemistry. Our work provides new insights about calcium-binding proteins and neuropeptide distribution in Octopus retina and suggests a functional role for calretinin, a highly conserved protein, in visual signal transduction of cephalopods. © 2018 Wiley Periodicals, Inc. Altobelli Giovanna G GG Department of Advanced Biomedical Sciences, Federico II University of Naples, Naples, Italy. Van Noorden Susan S Department of Histopathology, Imperial College London, London, UK. Cimini Vincenzo V 0000-0003-4767-2771 Department of Advanced Biomedical Sciences, Federico II University of Naples, Naples, Italy. eng Journal Article 2018 04 22

United States J Cell Physiol 0050222 0021-9541 0 Calbindin 2 0 Calbindins 0 Neuropeptides IM Animals Brain metabolism Calbindin 2 metabolism Calbindins metabolism Immunohistochemistry methods In Situ Hybridization methods Neuropeptides metabolism Octopodiformes metabolism Retina metabolism pathology Retinal Ganglion Cells metabolism pathology calretinin histochemistry neuropeptides octopus retina 2017 11 13 2018 02 27 2018 4 24 6 0 2019 10 1 6 0 2018 4 24 6 0 ppublish 29682745 10.1002/jcp.26570 27990638 2017 05 15 2017 05 15

1097-4652 232 7 2017 Jul J. Cell. Physiol. Calretinin Immunoreactivity in the Human Testis Throughout Fetal Life. 1872-1878 10.1002/jcp.25727 The main functions of the testis are sex hormone and sperm cell production. Steroidogenesis occurs in the Leydig interstitial cells and spermatogenesis in the seminiferous tubules. Male gonad morphogenesis is a finely orchestrated process, mainly coordinated by hormones, whose actions can significantly affect post-pubertal testicular function. Calcium is a key intracellular messenger, which regulates many signal transduction pathways, and is also implicated in steroidogenesis. Calcium homeostasis and signaling rely on many calcium-binding proteins including calretinin, of the "EF-hand" protein family. Calretinin is a highly conserved protein mainly expressed in the nervous system but also detected in rat and human adult and fetal testis as well as in pathological conditions. Calretinin expression in the fetal testis, however, has not been thoroughly analyzed probably owing to limited availability and paucity of tissues. Here, we examined by immunocytochemistry the expression of calretinin in human fetal testis specimens, obtained from natural and therapeutic abortions, at various developmental ages. We found that calretinin-immunoreactive Leydig cells were visible throughout the timeframe studied (14th-27th week). Immunoreactivity was also observed in Sertoli cells and in the germ cells of the immature seminiferous tubules. Overall our data indicate that calretinin expression parallels the decline in Leydig cell number, suggesting that its presence is indeed correlated to their steroidogenic activity. They also suggest that the intratubular positivity of calretinin could be linked to the ability of Sertoli cells to produce locally acting hormones contributing to the histodifferentiation of the male genital tract. J. Cell. Physiol. 232: 1872-1878, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc. Altobelli Giovanna G GG Department of Advanced Biomedical Sciences, Medical School, Federico II University of Naples, Naples, Italy. Pentimalli Francesca F Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Department of Biology, Temple University, Philadelphia, Pennsylvania. D'Armiento Mariarosaria M Department of Advanced Biomedical Sciences, Medical School, Federico II University of Naples, Naples, Italy. Van Noorden Susan S Department of Histopathology, Imperial College London, Hammersmith Hospital, London, United Kingdom. Cimini Vincenzo V Department of Advanced Biomedical Sciences, Medical School, Federico II University of Naples, Naples, Italy. eng Journal Article 2017 01 05

United States J Cell Physiol 0050222 0021-9541 0 Calbindin 2 0 Estrogen Receptor alpha IM Calbindin 2 metabolism Child Epididymis cytology metabolism Estrogen Receptor alpha metabolism Fetus cytology metabolism Gestational Age Humans Immunohistochemistry Leydig Cells cytology metabolism Male Puberty Testis cytology embryology metabolism 2016 11 18 2016 12 05 2016 12 19 6 0 2017 5 16 6 0 2016 12 20 6 0 ppublish 27990638 10.1002/jcp.25727 25813826 2016 02 09 2015 05 13

1872-6240 1610 2015 Jun 12 Brain Res. Analysis of calretinin early expression in the rat hippocampus after beta amyloid (1-42) peptide injection. 89-97 10.1016/j.brainres.2015.03.029 S0006-8993(15)00226-7 It has already been reported that cannabinoids are neuroprotective agents against excitotoxicity in vitro and increase after acute brain damage in vivo. This background prompted us to study the localization and expression of the calcium -binding protein calretinin in a condition similar to Alzheimer disease and its possible relationship with cannabinoids and their supposed protective role. We carried out quantitative analysis of the transient changes in calretinin expression shown by hybridochemistry within neuronal cell populations in the hippocampus of a beta amyloid-treated rat model of Alzheimer's disease and their correlation with endocannabinoid increase. Calretinin expression increases throughout the first week after cortical amyloid-beta peptide injection, and then decreases towards normal levels in the rat hippocampus during the following weeks, indicating that decreased calretinin gene expression may be associated with either increase of endocannabinoids or VDM11-induced accumulation of endocannabinoids. In contrast, SR1, an antagonist, which limits the cannabinoid effect by selective binding to the cannabinoid receptor CB1, up-regulates calretinin expression with respect to non-treated rats. This could mean that the SR1 endocannabinoid-blocking action through CB1 receptors, that are normally stimulated by endocannabinoids to inhibit calcium increase, might cause a higher calretinin expression. This would allow us to speculate on a possible reverse relationship between endocannabinoid and calretinin levels in the hippocampal calcium-homeostasis balance. Copyright © 2015 Elsevier B.V. All rights reserved. Altobelli Giovanna Giuseppina GG Department of Advanced Biomedical Sciences, School of Medicine and Surgery, University of Naples "Federico II", Via Pansini 5, 80131 Napoli, Italy. Electronic address: ggaltobe@unina.it. Cimini Donatella D Department of Experimental Medicine, Second University of Naples, Via Santa Maria di Costantinopoli 16, 80138 Napoli, Italy. Electronic address: donatella.cimini@unina2.it. Esposito Giuseppe G Department of Pharmacy, University of Naples "Federico II", Via Montesano 49, 80131 Napoli, Italy. Electronic address: giuseppe.esposito@uniroma1.it. Iuvone Teresa T Department of Pharmacy, University of Naples "Federico II", Via Montesano 49, 80131 Napoli, Italy. Electronic address: teresa.iuvone@unina.it. Cimini Vincenzo V Department of Advanced Biomedical Sciences, School of Medicine and Surgery, University of Naples "Federico II", Via Pansini 5, 80131 Napoli, Italy. Electronic address: cimini@unina.it. eng Journal Article Research Support, Non-U.S. Gov't 2015 03 23

Netherlands Brain Res 0045503 0006-8993 0 Amyloid beta-Peptides 0 Calb2 protein, rat 0 Calbindin 2 0 Endocannabinoids 0 Peptide Fragments 0 RNA, Messenger 0 Receptor, Cannabinoid, CB1 0 amyloid beta-protein (1-42) IM Alzheimer Disease metabolism Amyloid beta-Peptides toxicity Animals Calbindin 2 metabolism Disease Models, Animal Endocannabinoids metabolism Gene Expression Hippocampus drug effects metabolism Male Peptide Fragments toxicity RNA, Messenger metabolism Random Allocation Rats, Wistar Receptor, Cannabinoid, CB1 metabolism Time Factors Alzheimer disease Amyloid beta peptide Calretinin Endocannabinoids Hippocampus In situ hybridization 2014 12 09 2015 03 14 2015 3 28 6 0 2015 3 31 6 0 2016 2 10 6 0 ppublish 25813826 S0006-8993(15)00226-7 10.1016/j.brainres.2015.03.029 23707017 2014 03 13 2013 05 27

1531-6564 38 6 2013 Jun J Hand Surg Am Adductor pollicis jamming injuries in the professional baseball player: 2 case reports. 1181-4 10.1016/j.jhsa.2013.03.042 S0363-5023(13)00431-0 We characterize a mechanism of injury, injury pattern, and treatment algorithm for adductor pollicis myotendinous injuries in 2 professional baseball players. Similar to myotendinous eccentric injuries in other anatomical areas, the adductor pollicis sustains a sudden forceful eccentric load during a jammed swing, resulting in intramuscular strain or tendon rupture. Based on the reported injury mechanism, and magnetic resonance imaging features of these myotendinous injuries, the thumb of the top hand during a jammed swing was suddenly and forcefully eccentrically abducted from a contracted and adducted position, resulting in injury patterns. Copyright © 2013. Published by Elsevier Inc. Altobelli Grant G GG Department of Orthopaedic Surgery, Tufts Medical Center, Boston, MA02462, USA. Ruchelsman David E DE Belsky Mark R MR Graham Thomas T Asnis Peter P Leibman Matthew I MI eng Case Reports Journal Article

United States J Hand Surg Am 7609631 0363-5023 IM Adult Baseball injuries physiology Biomechanical Phenomena Hand Strength Humans Magnetic Resonance Imaging Male Muscle Contraction Muscle, Skeletal injuries pathology surgery Occupational Diseases Orthopedic Procedures methods Orthotic Devices Rupture Suture Techniques Thumb injuries 2012 10 11 2013 03 20 2013 03 21 2013 5 28 6 0 2013 5 28 6 0 2014 3 14 6 0 ppublish 23707017 S0363-5023(13)00431-0 10.1016/j.jhsa.2013.03.042 23707008 2014 03 13 2013 05 27

1531-6564 38 6 2013 Jun J Hand Surg Am Outcomes of digital zone IV and V and thumb zone TI to TIV extensor tendon repairs using a running interlocking horizontal mattress technique. 1079-83 10.1016/j.jhsa.2013.03.031 S0363-5023(13)00420-6 Biomechanical evidence has demonstrated that the running interlocking horizontal mattress (RIHM) repair for extensor tendon lacerations is significantly stronger, with higher ultimate load to failure and less tendon shortening compared with other techniques. We investigated the efficacy and safety of primary extensor tendon repair using the RIHM repair technique in the fingers followed by the immediate controlled active motion protocol, and in the thumb followed by a dynamic extension protocol. We conducted a retrospective review of all patients undergoing extensor tendon repair from August 2009 to April 2012 by single surgeon in an academic hand surgery practice. The inclusion criteria were simple extensor tendon lacerations in digital zones IV and V and thumb zones TI to TIV and primary repair performed using the RIHM technique. We included 8 consecutive patients with 9 tendon lacerations (3 in the thumb). One patient underwent a concomitant dorsal hand rotation flap for soft tissue coverage. We used a 3-0 nonabsorbable braided suture to perform a running simple suture in 1 direction to obtain a tension-free tenorrhaphy, followed by an RIHM corset-type suture using the same continuous strand in the opposite direction. Average time to surgery was 10 days (range, 3-33 d). Mean follow-up was 15 weeks (range, 10-26 wk). We applied the immediate controlled active motion protocol to all injuries except those in the thumb, where we used a dynamic extension protocol instead. Using the criteria of Miller, all 9 tendon repairs achieved excellent or good results. There were no tendon ruptures or extensor lags. No patients required secondary surgery for tenolysis or joint release. No wound complications occurred. The RIHM technique for primary extensor tendon repairs in zone IV and V and T1 to TIV is safe, allows for immediate controlled active motion in the fingers and an immediate dynamic extension protocol in the thumb, and achieves good to excellent functional outcomes. These clinical outcomes support prior biomechanical data. Therapeutic IV. Copyright © 2013 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved. Altobelli Grant G GG Division of Hand and Upper Extremity Surgery, Tufts Medical Center and Newton-Wellesley Hospital/Tufts University School of Medicine, Boston, MA02462, USA. Conneely Stacy S Haufler Christina C Walsh Maura M Ruchelsman David E DE eng Journal Article

United States J Hand Surg Am 7609631 0363-5023 IM Adult Female Humans Lacerations surgery Male Middle Aged Orthopedic Procedures Retrospective Studies Surgical Flaps Suture Techniques Tendon Injuries surgery Young Adult 2012 08 29 2013 03 09 2013 03 18 2013 5 28 6 0 2013 5 28 6 0 2014 3 14 6 0 ppublish 23707008 S0363-5023(13)00420-6 10.1016/j.jhsa.2013.03.031 23688674 2013 12 03 2018 11 13

2047-9980 2 3 2013 May 20 J Am Heart Assoc Genetic deletion of uncoupling protein 3 exaggerates apoptotic cell death in the ischemic heart leading to heart failure. e000086 10.1161/JAHA.113.000086 Uncoupling protein 3 (ucp3) is a member of the mitochondrial anion carrier superfamily of proteins uncoupling mitochondrial respiration. In this study, we investigated the effects of ucp3 genetic deletion on mitochondrial function and cell survival under low oxygen conditions in vitro and in vivo. To test the effects of ucp3 deletion in vitro, murine embryonic fibroblasts and adult cardiomyocytes were isolated from wild-type (WT, n=67) and ucp3 knockout mice (ucp3(-/-), n=70). To test the effects of ucp3 genetic deletion in vivo, myocardial infarction (MI) was induced by permanent coronary artery ligation in WT and ucp3(-/-) mice. Compared with WT, ucp3(-/-) murine embryonic fibroblasts and cardiomyocytes exhibited mitochondrial dysfunction and increased mitochondrial reactive oxygen species generation and apoptotic cell death under hypoxic conditions in vitro (terminal deoxynucleotidyl transferase-dUTP nick end labeling-positive nuclei: WT hypoxia, 70.3 ± 1.2%; ucp3(-/-) hypoxia, 85.3 ± 0.9%; P<0.05). After MI, despite similar areas at risk in the 2 groups, ucp3(-/-) hearts demonstrated a significantly larger infarct size compared with WT (infarct area/area at risk: WT, 48.2 ± 3.7%; ucp3(-/-), 65.0 ± 2.9%; P<0.05). Eight weeks after MI, cardiac function was significantly decreased in ucp3(-/-) mice compared with WT (fractional shortening: WT MI, 42.7 ± 3.1%; ucp3(-/-) MI, 24.4 ± 2.9; P<0.05), and this was associated with heightened apoptotic cell death (terminal deoxynucleotidyl transferase-dUTP nick end labeling-positive nuclei: WT MI, 0.7 ± 0.04%; ucp3(-/-) MI, 1.1 ± 0.09%, P<0.05). Our data indicate that ucp3 levels regulate reactive oxygen species levels and cell survival during hypoxia, modulating infarct size in the ischemic heart. Perrino Cinzia C Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy. Schiattarella Gabriele G GG Sannino Anna A Pironti Gianluigi G Petretta Maria Piera MP Cannavo Alessandro A Gargiulo Giuseppe G Ilardi Federica F Magliulo Fabio F Franzone Anna A Carotenuto Giuseppe G Serino Federica F Altobelli Giovanna G GG Cimini Vincenzo V Cuocolo Alberto A Lombardi Assunta A Goglia Fernando F Indolfi Ciro C Trimarco Bruno B Esposito Giovanni G eng Journal Article Research Support, Non-U.S. Gov't 2013 05 20

England J Am Heart Assoc 101580524 2047-9980 0 Ion Channels 0 Mitochondrial Proteins 0 Reactive Oxygen Species 0 Ucp3 protein, mouse 0 Uncoupling Protein 3 IM Animals Apoptosis genetics Cells, Cultured Female Gene Deletion Heart Failure etiology genetics metabolism Ion Channels genetics Male Mice Mitochondrial Proteins genetics Myocardial Ischemia complications genetics metabolism Reactive Oxygen Species metabolism Uncoupling Protein 3 cardiac remodeling free radicals mitochondria uncoupling protein 2013 5 22 6 0 2013 5 22 6 0 2013 12 16 6 0 epublish 23688674 2/3/e000086 10.1161/JAHA.113.000086 PMC3698767 J Am Coll Cardiol. 2011 Jan 18;57(3):310-2 21232668 Basic Res Cardiol. 2010 Nov;105(6):771-85 20960209 Basic Res Cardiol. 2011 Jun;106(4):577-89 21369867 Arterioscler Thromb Vasc Biol. 2011 Aug;31(8):1757-65 21597006 Free Radic Biol Med. 2011 Sep 15;51(6):1106-15 21762777 Circulation. 2011 Sep 6;124(10):1172-9 21900096 J Biol Chem. 2011 Sep 16;286(37):32533-41 21775425 Eur J Heart Fail. 2011 Dec;13(12):1264-74 22045926 J Nucl Cardiol. 2012 Jun;19(3):492-9 22395780 Basic Res Cardiol. 2012 Sep;107(5):296 22890560 N Engl J Med. 2000 Jan 20;342(3):154-60 10639540 J Biol Chem. 2000 May 26;275(21):16258-66 10748196 Cardiovasc Res. 2000 Jul;47(1):68-73 10869531 Am J Physiol Heart Circ Physiol. 2000 Jul;279(1):H429-36 10899083 FASEB J. 2001 Mar;15(3):833-45 11259402 IUBMB Life. 2001 Sep-Nov;52(3-5):181-8 11798031 J Mol Cell Cardiol. 2002 May;34(5):555-69 12056859 J Clin Invest. 2005 Mar;115(3):500-8 15765131 Am J Cardiol. 1998 Aug 6;82(3A):21H-24H 9719018 Circulation. 1995 Aug 1;92(3):334-41 7634446 Free Radic Biol Med. 2004 Sep 15;37(6):755-67 15304252 Circ Res. 2003 Aug 8;93(3):192-200 12855674 Circulation. 2003 Feb 25;107(7):947-53 12600905 Cardiology. 2002;97(4):203-9 12145475 Nat Cell Biol. 2008 Nov;10(11):1235-7; author reply 1237-40 18978830 Biochem Soc Symp. 2004;(71):203-13 15777023 Biochim Biophys Acta. 2005 Sep 5;1709(2):150-6 16084485 J Neurochem. 2005 Sep;94(6):1676-84 16045446 Am J Physiol Regul Integr Comp Physiol. 2006 Apr;290(4):R894-903 16293682 Eur Heart J. 2006 Apr;27(7):875-81 16434410 Biochem J. 2006 May 1;395(3):611-8 16436046 Biochem Biophys Res Commun. 2006 May 19;343(4):1060-6 16579967 Am J Physiol Heart Circ Physiol. 2006 Oct;291(4):H1754-60 16699071 Mol Cell Biochem. 2006 Oct;290(1-2):153-8 16718365 Cardiovasc Res. 2006 Nov 1;72(2):210-9 16914124 J Mol Cell Cardiol. 2006 Dec;41(6):980-8 16926020 FASEB J. 2007 Feb;21(2):312-24 17202247 Nat Cell Biol. 2007 Apr;9(4):445-52 17351641 Am J Physiol Heart Circ Physiol. 2007 Jul;293(1):H829-35 17468330 Heart. 2007 Sep;93(9):1137-46 17699180 Lancet. 2002 Jul 6;360(9326):23-33 12114037 Cardiovasc Res. 2008 Dec 1;80(3):416-24 18697792 FEBS Lett. 2008 Dec 24;582(30):4147-52 19041310 Cardiovasc Res. 2009 Feb 15;81(3):449-56 18854381 Cardiology. 2009;112(3):219-23 18698138 J Bioenerg Biomembr. 2009 Aug;41(4):335-42 19705265 Trends Biochem Sci. 2010 May;35(5):298-307 20006514 Cancer Chemother Pharmacol. 2010 Jul;66(2):303-14 19915844 Br J Pharmacol. 2010 Jul;160(6):1408-16 20590631 Cardiovasc Res. 2010 Oct 1;88(1):101-10 20511238 Basic Res Cardiol. 2010 Nov;105(6):677-86 20865418 Cancer Chemother Pharmacol. 2011 Jun;67(6):1381-8 20809120 22452704 2012 12 10 2018 11 13

1476-5381 166 8 2012 Aug Br. J. Pharmacol. Myocardial β(2) -adrenoceptor gene delivery promotes coordinated cardiac adaptive remodelling and angiogenesis in heart failure. 2348-61 10.1111/j.1476-5381.2012.01954.x We investigated whether β(2) -adrenoceptor overexpression could promote angiogenesis and improve blood perfusion and left ventricular (LV) remodeling of the failing heart. We explored the angiogenic effects of β(2) -adrenoceptor overexpression in a rat model of post-myocardial infarction (MI) heart failure (HF). Cardiac adenoviral-mediated β(2) -adrenoceptor overexpression was obtained via direct intramyocardial injection 4-weeks post-MI. Adenovirus(Ad)-GFP and saline injected rats served as controls. Furthermore, we extended our observation to β(2) -adrenoceptor -/- mice undergoing MI. Transgenes were robustly expressed in the LV at 2 weeks post-gene therapy, whereas their expression was minimal at 4-weeks post-gene delivery. In HF rats, cardiac β(2) -adrenoceptor overexpression resulted in enhanced basal and isoprenaline-stimulated cardiac contractility at 2-weeks post-gene delivery. At 4 weeks post-gene transfer, Ad-β(2) -adrenoceptor HF rats showed improved LV remodeling and cardiac function. Importantly, β(2) -adrenoceptor overexpression was associated with a markedly increased capillary and arteriolar length density and enhanced in vivo myocardial blood flow and coronary reserve. At the molecular level, cardiac β(2) -adrenoceptor gene transfer induced the activation of the VEGF/PKB/eNOS pro-angiogenic pathway. In β(2) -adrenoceptor-/- mice, we found a ~25% reduction in cardiac capillary density compared with β(2) -adrenoceptor+/+ mice. The lack of β(2) -adrenoceptors was associated with a higher mortality rate at 30 days and LV dilatation, and a worse global cardiac contractility compared with controls. β(2) -Adrenoceptors play an important role in the regulation of the angiogenic response in HF. The activation of VEGF/PKB/eNOS pathway seems to be strongly involved in this mechanism. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society. Rengo G G Salvatore Maugeri Foundation, IRCCS, Telese Terme (BN), Italy. Zincarelli C C Femminella G D GD Liccardo D D Pagano G G de Lucia C C Altobelli G G GG Cimini V V Ruggiero D D Perrone-Filardi P P Gao E E Ferrara N N Lymperopoulos A A Koch W J WJ Leosco D D eng R01 HL085503 HL NHLBI NIH HHS United States Journal Article Research Support, Non-U.S. Gov't

England Br J Pharmacol 7502536 0007-1188 0 Receptors, Adrenergic, beta-2 IM Animals Gene Expression Regulation Gene Transfer Techniques Genetic Therapy methods Mice Mice, Knockout Myocardial Contraction Myocardial Reperfusion Myocardium Neovascularization, Physiologic Rats Receptors, Adrenergic, beta-2 genetics Ventricular Remodeling 2012 3 29 6 0 2012 3 29 6 0 2012 12 12 6 0 ppublish 22452704 10.1111/j.1476-5381.2012.01954.x PMC3448898 Am J Physiol Heart Circ Physiol. 2010 Jun;298(6):H2032-8 20304818 J Biol Chem. 2010 May 21;285(21):16378-86 20351116 Br J Pharmacol. 2010 Aug;160(7):1573-6 20649560 Br J Pharmacol. 2010 Aug;160(7):1577-9 20649561 Circ Res. 2010 Oct 29;107(9):1140-9 20814022 Br J Pharmacol. 2011 Feb;162(3):712-21 20958287 J Mol Cell Cardiol. 2011 May;50(5):785-92 20800067 Circulation. 1999 Nov 30;100(22):2210-2 10577992 Circulation. 2000 Apr 11;101(14):1707-14 10758054 J Biol Chem. 2000 May 12;275(19):14466-75 10799529 Circulation. 2000 Jul 18;102(3):344-50 10899100 Proc Natl Acad Sci U S A. 2001 Feb 13;98(4):1607-12 11171998 Nature. 2002 Jan 10;415(6868):206-12 11805844 Circulation. 2002 Jul 2;106(1):124-9 12093781 Circ Res. 2003 Nov 14;93(10):896-906 14615493 Trends Pharmacol Sci. 2004 Jul;25(7):358-65 15219978 Circulation. 2004 Aug 31;110(9):1083-90 15313944 Nature. 1967 May 6;214(5088):597-8 6036174 Circ Res. 1986 Jan;58(1):26-37 3943155 Circulation. 1990 Jan;81(1):238-46 2137045 Circulation. 1993 Feb;87(2):454-63 8381058 Cell. 1993 Aug 13;74(3):409-12 8394218 Circ Res. 1994 Feb;74(2):206-13 8293560 Science. 1994 Apr 22;264(5158):582-6 8160017 Proc Natl Acad Sci U S A. 1999 May 25;96(11):6400-5 10339599 J Biol Chem. 1999 Jun 11;274(24):16701-8 10358009 J Clin Invest. 1999 Jul;104(1):21-9 10393695 FASEB J. 2005 Jun;19(8):983-5 15802488 Circulation. 2005 May 31;111(21):2837-49 15927992 J Clin Invest. 2005 Aug;115(8):2108-18 16075055 Nat Med. 2005 Sep;11(9):952-8 16142243 Circ Res. 2005 Sep 16;97(6):507-9 16166560 Nat Clin Pract Cardiovasc Med. 2005 Sep;2(9):475-83 16265588 Am J Physiol Heart Circ Physiol. 2005 Dec;289(6):H2441-9 16040722 Circ Res. 2005 Nov 25;97(11):1182-9 16239589 J Pharmacol Exp Ther. 2006 May;317(2):553-61 16421285 Genes Dev. 2006 Dec 15;20(24):3347-65 17182864 Nat Med. 2007 Mar;13(3):315-23 17322894 Am J Physiol Heart Circ Physiol. 2007 Sep;293(3):H1596-603 17557919 Trends Mol Med. 2007 Dec;13(12):503-11 17981507 Mol Ther. 2008 Feb;16(2):302-7 18223549 Cardiovasc Res. 2008 May 1;78(2):385-94 18093988 Circulation. 2009 Jan 6;119(1):89-98 19103992 Proc Natl Acad Sci U S A. 2009 Apr 7;106(14):5825-30 19289825 J Am Coll Cardiol. 2009 Nov 3;54(19):1747-62 19874988 Clin Transl Sci. 2010 Jun;3(3):81-9 20590676 21459790 2011 10 26 2018 11 13

1592-8721 96 7 2011 Jul Haematologica LMO2 expression reflects the different stages of blast maturation and genetic features in B-cell acute lymphoblastic leukemia and predicts clinical outcome. 980-6 10.3324/haematol.2011.040568 LMO2 is highly expressed at the most immature stages of lymphopoiesis. In T-lymphocytes, aberrant LMO2 expression beyond those stages leads to T-cell acute lymphoblastic leukemia, while in B cells LMO2 is also expressed in germinal center lymphocytes and diffuse large B-cell lymphomas, where it predicts better clinical outcome. The implication of LMO2 in B-cell acute lymphoblastic leukemia must still be explored. We measured LMO2 expression by real time RT-PCR in 247 acute lymphoblastic leukemia patient samples with cytogenetic data (144 of them also with survival and immunophenotypical data) and in normal hematopoietic and lymphoid cells. B-cell acute lymphoblastic leukemia cases expressed variable levels of LMO2 depending on immunophenotypical and cytogenetic features. Thus, the most immature subtype, pro-B cells, displayed three-fold higher LMO2 expression than pre-B cells, common-CD10+ or mature subtypes. Additionally, cases with TEL-AML1 or MLL rearrangements exhibited two-fold higher LMO2 expression compared to cases with BCR-ABL rearrangements or hyperdyploid karyotype. Clinically, high LMO2 expression correlated with better overall survival in adult patients (5-year survival rate 64.8% (42.5%-87.1%) vs. 25.8% (10.9%-40.7%), P= 0.001) and constituted a favorable independent prognostic factor in B-ALL with normal karyotype: 5-year survival rate 80.3% (66.4%-94.2%) vs. 63.0% (46.1%-79.9%) (P= 0.043). Our data indicate that LMO2 expression depends on the molecular features and the differentiation stage of B-cell acute lymphoblastic leukemia cells. Furthermore, assessment of LMO2 expression in adult patients with a normal karyotype, a group which lacks molecular prognostic factors, could be of clinical relevance. Malumbres Raquel R Division of Oncology, Center for Applied Medical Research (CIMA) University of Navarra, Pamplona, Spain. Fresquet Vicente V Roman-Gomez Jose J Bobadilla Miriam M Robles Eloy F EF Altobelli Giovanna G GG Calasanz M José MJ Smeland Erlend B EB Aznar Maria Angela MA Agirre Xabier X Martin-Palanco Vanesa V Prosper Felipe F Lossos Izidore S IS Martinez-Climent Jose A JA eng R01 CA109335 CA NCI NIH HHS United States R01 CA122105 CA NCI NIH HHS United States Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't 2011 04 01

Italy Haematologica 0417435 0390-6078 0 Adaptor Proteins, Signal Transducing 0 DNA-Binding Proteins 0 LIM Domain Proteins 0 LMO2 protein, human 0 Metalloproteins 0 Proto-Oncogene Proteins IM Adaptor Proteins, Signal Transducing Adolescent Adult Age Factors Aged Aged, 80 and over B-Lymphocyte Subsets metabolism Cell Differentiation genetics Cell Line, Tumor Child Child, Preschool DNA-Binding Proteins genetics Gene Expression Regulation, Leukemic Humans Immunophenotyping Infant Karyotyping LIM Domain Proteins Metalloproteins genetics Middle Aged Precursor B-Cell Lymphoblastic Leukemia-Lymphoma diagnosis genetics metabolism mortality Precursor T-Cell Lymphoblastic Leukemia-Lymphoma genetics Prognosis Proto-Oncogene Proteins Survival Analysis Treatment Outcome Young Adult 2011 4 5 6 0 2011 4 5 6 0 2011 10 27 6 0 ppublish 21459790 haematol.2011.040568 10.3324/haematol.2011.040568 PMC3128216 Blood. 2010 Aug 12;116(6):962-70 20519628 Hematology. 2010 Jun;15(3):132-4 20557670 Blood. 2002 Mar 1;99(5):1536-43 11861265 Leukemia. 2003 Apr;17(4):789-95 12682639 Leukemia. 2003 Dec;17(12):2474-86 14562124 N Engl J Med. 2004 Feb 26;350(9):913-22 14985489 Proc Natl Acad Sci U S A. 1991 May 15;88(10):4367-71 2034676 Oncogene. 1992 Dec;7(12):2389-97 1461647 Science. 1997 Nov 7;278(5340):1059-64 9353180 Proc Natl Acad Sci U S A. 1998 Mar 31;95(7):3890-5 9520463 EMBO J. 1998 Aug 17;17(16):4594-605 9707419 Blood. 1999 May 1;93(9):2780-90 10216071 Mol Cell Biol. 1999 Jun;19(6):4443-51 10330184 Oncogene. 2006 Mar 23;25(13):1862-70 16314841 Blood. 2006 Nov 15;108(10):3520-9 16873670 J Clin Oncol. 2007 Jan 1;25(1):16-24 17194902 Blood. 2007 Feb 15;109(4):1636-42 17038524 Nature. 2007 Apr 12;446(7137):758-64 17344859 J Clin Oncol. 2008 Jan 20;26(3):447-54 18086797 Lancet. 2008 Mar 22;371(9617):1030-43 18358930 J Clin Invest. 2008 Sep;118(9):3132-42 18688285 Curr Opin Pediatr. 2009 Feb;21(1):1-8 19242236 Neoplasia. 2009 Jul;11(7):712-9 19568416 Hematology. 2009 Aug;14(4):220-3 19635185 Haematologica. 2002 Feb;87(2):154-66 11836166 21423374 2011 05 09 2018 11 13

1664-042X 1 2010 Front Physiol Effects of propionyl-L-carnitine on ischemia-reperfusion injury in hamster cheek pouch microcirculation. 132 10.3389/fphys.2010.00132 Propionyl-l-carnitine (pLc) exerts protective effects in different experimental models of ischemia-reperfusion (I/R). The aim of the present study was to assess the effects of intravenously and topically applied pLc on microvascular permeability increase induced by I/R in the hamster cheek pouch preparation. The hamster cheek pouch microcirculation was visualized by fluorescence microscopy. Microvascular permeability, leukocyte adhesion to venular walls, perfused capillary length, and capillary red blood cell velocity (V(RBC)) were evaluated by computer-assisted methods. E-selectin expression was assessed by in vitro analysis. Lipid peroxidation and reactive oxygen species (ROS) formation were determined by thiobarbituric acid-reactive substances (TBARS) and 2'-7'-dichlorofluorescein (DCF), respectively. In control animals, I/R caused a significant increase in permeability and in the leukocyte adhesion in venules. Capillary perfusion and V(RBC) decreased. TBARS levels and DCF fluorescence significantly increased compared with baseline. Intravenously infused pLc dose-dependently prevented leakage and leukocyte adhesion, preserved capillary perfusion, and induced vasodilation at the end of reperfusion, while ROS concentration decreased. Inhibition of nitric oxide synthase prior to pLc caused vasoconstriction and partially blunted the pLc-induced protective effects; inhibition of the endothelium-derived hyperpolarizing factor (EDHF) abolished pLc effects. Topical application of pLc on cheek pouch membrane produced the same effects as observed with intravenous administration. pLc decreased the E-selectin expression. pLc prevents microvascular changes induced by I/R injury. The reduction of permeability increase could be mainly due to EDHF release induce vasodilatation together with NO. The reduction of E-selectin expression prevents leukocyte adhesion and permeability increase. Lapi Dominga D Department of Neuroscience, "Federico II" University Medical School of Naples Naples, Italy. d.lapi@dfb.unipi.it Sabatino Lina L Altobelli Giovanna Giuseppina GG Mondola Paolo P Cimini Vincenzo V Colantuoni Antonio A eng Journal Article 2010 10 19

Switzerland Front Physiol 101549006 1664-042X 2′-7′-dichlorofluorescein (DCF) E-selectin endothelium-derived hyperpolarizing factor (EDHF) ischemia–reperfusion lipid peroxides microcirculation nitric oxide synthase propionyl-l-carnitine 2010 03 22 2010 08 23 2011 3 23 6 0 2010 1 1 0 0 2010 1 1 0 1 epublish 21423374 10.3389/fphys.2010.00132 PMC3059950 Dev Dyn. 2000 Sep;219(1):63-76 10974672 Angiology. 2006 Mar-Apr;57(2):145-54 16518521 J Surg Res. 2005 May 1;125(1):16-22 15836845 Eur Heart J. 2007 Mar;28(5):608-12 17298965 Mol Cell Biochem. 1989 Jun 27-Jul 24;88(1-2):161-8 2779535 Drugs Exp Clin Res. 1991;17(3):191-6 1914846 Atherosclerosis. 2001 Jun;156(2):321-7 11395028 Ann N Y Acad Sci. 1971 Jun 21;177:5-9 4400556 Drugs Aging. 1998 Mar;12(3):243-8; discussion 249-50 9534023 Microcirculation. 1999 Sep;6(3):167-78 10501090 Am J Physiol Gastrointest Liver Physiol. 2004 May;286(5):G769-76 14715524 Kidney Int. 2002 Mar;61(3):1064-78 11849462 Cardiovasc Drugs Ther. 1991 Feb;5 Suppl 1:77-83 2031875 Am J Physiol Heart Circ Physiol. 2007 Jun;292(6):H2737-44 17220192 Am J Physiol Heart Circ Physiol. 2000 Mar;278(3):H755-61 10710343 Brain Res Bull. 1998 Mar 15;45(5):517-20 9570722 Arch Biochem Biophys. 1991 Aug 1;288(2):533-7 1654837 J Vasc Res. 2007;44(5):354-64 17483601 Blood. 1999 Dec 1;94(11):3820-8 10572097 J Lab Clin Med. 1995 May;125(5):626-33 7537789 Cardiology. 2006;106(4):215-23 16685128 Circ Res. 1998 Aug 10;83(3):287-94 9710121 Cardiovasc Drugs Ther. 1991 Feb;5 Suppl 1:107-11 2031868 Blood. 1994 Oct 1;84(7):2068-101 7522621 Pharmacol Res. 2001 Oct;44(4):305-9 11592865 20020337 2010 06 15 2018 11 13

1528-1132 468 5 2010 May Clin. Orthop. Relat. Res. Cost analysis of outpatient anterior cruciate ligament reconstruction: autograft versus allograft. 1418-22 10.1007/s11999-009-1178-y Prior studies suggest the cost of allograft anterior cruciate ligament (ACL) reconstruction is less than that for autograft reconstruction. Charges in these studies were influenced by patients requiring inpatient hospitalization. QUESTION/PURPOSE: We therefore determined if allograft ACL reconstruction would still be less costly if all procedures were performed in a completely outpatient setting. We retrospectively reviewed 155 patients who underwent ACL reconstruction in an ambulatory surgery center between 2001 and 2004; 105 had an autograft and 50 had an allograft. Charges were extracted from itemized billing records, standardized to eliminate cost increases, and categorized for comparison. Surgeon and anesthesiologist fees were not included in the analysis. Groups were compared for age, gender, mean total cost, mean cost of implants, and several other cost categories. The mean total cost was $5465 for allograft ACL reconstruction and $4872 for autograft ACL reconstruction. There were no differences in complications between the two groups. Allograft ACL reconstruction was more costly than autograft ACL reconstruction in the outpatient setting. The cost of the allograft outweighs the increased surgical time needed for harvesting an autograft. Level II, economic and decision analyses. See Guidelines for Authors for a complete description of levels of evidence. Nagda Sameer H SH Anderson Orthopaedic Clinic, 2445 Army Navy Drive, Arlington, VA 22206, USA. Sameer.Nagda@gmail.com Altobelli Grant G GG Bowdry Kevin A KA Brewster Clive E CE Lombardo Stephen J SJ eng Comparative Study Journal Article Multicenter Study 2009 12 18

United States Clin Orthop Relat Res 0075674 0009-921X AIM IM Adolescent Adult Ambulatory Surgical Procedures economics Anterior Cruciate Ligament surgery Anterior Cruciate Ligament Injuries Costs and Cost Analysis Female Health Care Costs statistics & numerical data Humans Male Middle Aged Reconstructive Surgical Procedures economics methods Retrospective Studies Tendons transplantation Tibia transplantation Tissue Transplantation instrumentation methods Transplantation, Autologous economics Transplantation, Homologous economics United States Young Adult 2009 03 01 2009 11 12 2009 12 19 6 0 2009 12 19 6 0 2010 6 16 6 0 ppublish 20020337 10.1007/s11999-009-1178-y PMC2853669 Proc (Bayl Univ Med Cent). 2000 Oct;13(4):327-30 16389334 Clin Orthop Relat Res. 1996 Mar;(324):134-44 8595749 Am J Knee Surg. 2001 Summer;14(3):145-51 11491424 Arthroscopy. 1997 Dec;13(6):699-703 9442322 Arthroscopy. 1997 Aug;13(4):446-9 9276050 Arthroscopy. 2005 Jul;21(7):774-85 16012489 Arthroscopy. 2005 Jul;21(7):786-90 16012490 Knee. 2001 Mar;8(1):25-7 11248565 Arthroscopy. 1998 Sep;14(6):613-6 9754480 Orthopedics. 1998 Jul;21(7):781-4 9672915 J Bone Joint Surg Am. 2006 Mar;88(3):660-7 16510834 Arthroscopy. 1995 Apr;11(2):134-8 7794423 Arthroscopy. 1995 Apr;11(2):151-6 7794426 Arthroscopy. 2001 Jan;17(1):9-13 11154360 19505323 2009 11 04 2019 12 10

1479-5876 7 2009 Jun 08 J Transl Med In vivo properties of the proangiogenic peptide QK. 41 10.1186/1479-5876-7-41 The main regulator of neovascularization is Vascular Endothelial Growth Factor (VEGF). We recently demonstrated that QK, a de novo engineered VEGF mimicking peptide, shares in vitro the same biological properties of VEGF, inducing capillary formation and organization. On these grounds, the aim of this study is to evaluate in vivo the effects of this small peptide. Therefore, on Wistar Kyoto rats, we evaluated vasomotor responses to VEGF and QK in common carotid rings. Also, we assessed the effects of QK in three different models of angiogenesis: ischemic hindlimb, wound healing and Matrigel plugs. QK and VEGF present similar endothelium-dependent vasodilatation. Moreover, the ability of QK to induce neovascularization was confirmed us by digital angiographies, dyed beads dilution and histological analysis in the ischemic hindlimb as well as by histology in wounds and Matrigel plugs. Our findings show the proangiogenic properties of QK, suggesting that also in vivo this peptide resembles the full VEGF protein. These data open to new fields of investigation on the mechanisms of activation of VEGF receptors, offering clinical implications for treatment of pathophysiological conditions such as chronic ischemia. Santulli Gaetano G Dipartimento di Medicina Clinica, Scienze Cardiovascolari ed Immunologiche, Cattedra di Medicina Interna, Università degli Studi Federico II di Napoli, Italy. gaetanosantulli@libero.it Ciccarelli Michele M Palumbo Gianluigi G Campanile Alfonso A Galasso Gennaro G Ziaco Barbara B Altobelli Giovanna Giuseppina GG Cimini Vincenzo V Piscione Federico F D'Andrea Luca Domenico LD Pedone Carlo C Trimarco Bruno B Iaccarino Guido G eng Evaluation Study Journal Article 2009 06 08

England J Transl Med 101190741 1479-5876 0 Biocompatible Materials 0 Drug Combinations 0 Intercellular Signaling Peptides and Proteins 0 Laminin 0 Peptides 0 Proteoglycans 0 QK peptide, rat 0 Vascular Endothelial Growth Factor A 119978-18-6 matrigel 9007-34-5 Collagen IM Animals Biocompatible Materials metabolism Biomimetics Capillaries drug effects Carotid Artery, Common physiology Collagen metabolism Drug Combinations Endothelial Cells metabolism Endothelium, Vascular drug effects metabolism physiopathology Hindlimb blood supply metabolism physiopathology Intercellular Signaling Peptides and Proteins Ischemia physiopathology Laminin metabolism Male Neovascularization, Physiologic drug effects physiology Peptides chemistry drug effects metabolism pharmacology Protein Engineering Proteoglycans metabolism Rats Rats, Inbred WKY Vascular Endothelial Growth Factor A metabolism pharmacology Wound Healing physiology 2009 03 19 2009 06 08 2009 6 10 9 0 2009 6 10 9 0 2009 11 5 6 0 epublish 19505323 1479-5876-7-41 10.1186/1479-5876-7-41 PMC2702279 Circulation. 2001 Jul 3;104(1):115-9 11435348 Nat Med. 2001 Apr;7(4):425-9 11283668 J Vasc Surg. 2001 Sep;34(3):489-96 11533602 Circ Res. 2002 May 17;90(9):966-73 12016262 Cancer Cell. 2002 Feb;1(1):99-108 12086892 J Gene Med. 2002 Jul-Aug;4(4):371-80 12124979 Circulation. 2003 Mar 18;107(10):1359-65 12642354 Basic Res Cardiol. 2004 Mar;99(2):121-32 14963670 Circulation. 2004 Jun 1;109(21):2587-93 15136501 J Clin Invest. 1994 Feb;93(2):662-70 7509344 J Clin Invest. 1996 Dec 1;98(11):2507-11 8958213 Circulation. 2005 Sep 20;112(12):1813-24 16172288 Proc Natl Acad Sci U S A. 2005 Oct 4;102(40):14215-20 16186493 Circ Res. 2005 Nov 25;97(11):1182-9 16239589 Circ Res. 2006 Feb 3;98(2):254-61 16373599 FASEB J. 2006 May;20(7):970-2 16608872 Cell Signal. 2007 Sep;19(9):1949-55 17629454 Am J Physiol Heart Circ Physiol. 2007 Sep;293(3):H1596-603 17557919 J Cell Mol Med. 2007 Sep-Oct;11(5):1149-61 17979890 Br J Pharmacol. 2008 Mar;153(5):936-46 18084315 Chemistry. 2008;14(14):4164-6 18384035 Am J Physiol Gastrointest Liver Physiol. 2008 Aug;295(2):G374-81 18583458 Circ Res. 2008 Oct 24;103(9):1018-26 18757827 J Cardiovasc Med (Hagerstown). 2008 Dec;9(12):1190-221 19001927 Proc Natl Acad Sci U S A. 2008 Nov 18;105(46):17818-23 19008357 Nature. 2008 Dec 11;456(7223):809-13 18997771 Nature. 2008 Dec 11;456(7223):814-8 18997773 Basic Res Cardiol. 2009 Jan;104(1):5-21 19101749 J Vasc Surg. 2009 Feb;49(2):346-51 19028065 Nat Med. 2000 Jan;6(1):49-55 10613823 J Biol Chem. 2000 May 26;275(21):15905-11 10748050 Nat Med. 2000 Oct;6(10):1102-3 11017137 Proc Natl Acad Sci U S A. 2001 Feb 27;98(5):2604-9 11226286 Circ Res. 2001 Aug 31;89(5):389-400 11532899 19008357 2008 12 17 2018 11 13

1091-6490 105 46 2008 Nov 18 Proc. Natl. Acad. Sci. U.S.A. The G-protein-coupled receptor kinase 5 inhibits NFkappaB transcriptional activity by inducing nuclear accumulation of IkappaB alpha. 17818-23 10.1073/pnas.0804446105 G-protein-coupled receptor (GPCR) kinases, GRKs, are known as serine/threonine kinases that regulate GPCR signaling, but recent findings propose functions for these kinases besides receptor desensitization. Indeed, GRK5 can translocate to the nucleus by means of a nuclear localization sequence, suggesting that this kinase regulates transcription events in the nucleus. To evaluate the effect of GRK5-IkappaB alpha interaction on NFkappaB signaling, we induced the overexpression and the knockdown of GRK5 in cell cultures. GRK5 overexpression causes nuclear accumulation of IkappaB alpha, leading to the inhibition of NFkappaB transcriptional activity. Opposite results are achieved by GRK5 knockdown through siRNA. A physical interaction between GRK5 and IkappaB alpha, rather than phosphorylative events, appears as the underlying mechanism. We identify the regulator of gene protein signaling homology domain of GRK5 (RH) and the N-terminal domain of IkappaB alpha as the regions involved in such interaction. To confirm the biological relevance of this mechanism of regulation for NFkappaB, we evaluated the effects of GRK5-RH on NFkappaB-dependent phenotypes. In particular, GRK5-RH overexpression impairs apoptosis protection and cytokine production in vitro and inflammation and tissue regeneration in vivo. Our results reveal an unexpected role for GRK5 in the regulation of NFkappaB transcription activity. Placing these findings in perspective, this mechanism may represent a therapeutic target for all those conditions involving excessive NFkappaB activity. Sorriento Daniela D Dipartimento di Medicina Clinica, Scienze Cardiovascolari, ed Immunologiche, Università Federico II, 80134 Naples, Italy. Ciccarelli Michele M Santulli Gaetano G Campanile Alfonso A Altobelli Giovanna Giuseppina GG Cimini Vincenzo V Galasso Gennaro G Astone Dalila D Piscione Federico F Pastore Lucio L Trimarco Bruno B Iaccarino Guido G eng Journal Article Research Support, Non-U.S. Gov't 2008 11 13

United States Proc Natl Acad Sci U S A 7505876 0027-8424 0 I-kappa B Proteins 0 Lipopolysaccharides 0 NF-kappa B 0 NFKBIA protein, human 0 Nfkbia protein, rat 0 Tumor Necrosis Factor-alpha 139874-52-5 NF-KappaB Inhibitor alpha EC 2.7.11.16 G-Protein-Coupled Receptor Kinase 5 IM Adenoviridae Animals Apoptosis drug effects Cattle Cell Line Cell Movement drug effects Cell Nucleus drug effects metabolism Endothelial Cells cytology drug effects enzymology G-Protein-Coupled Receptor Kinase 5 chemistry metabolism Humans I-kappa B Proteins metabolism Lipopolysaccharides pharmacology NF-KappaB Inhibitor alpha NF-kappa B genetics Neovascularization, Physiologic drug effects Protein Binding drug effects Protein Interaction Mapping Protein Structure, Tertiary Rats Regeneration drug effects Transcription, Genetic drug effects Tumor Necrosis Factor-alpha metabolism 2008 11 15 9 0 2008 12 18 9 0 2008 11 15 9 0 ppublish 19008357 0804446105 10.1073/pnas.0804446105 PMC2584738 Proc Natl Acad Sci U S A. 2005 Feb 1;102(5):1442-7 15671181 Proc Natl Acad Sci U S A. 2005 Feb 1;102(5):1448-53 15671180 Nat Med. 2005 Sep;11(9):952-8 16142243 Circ Res. 2005 Nov 25;97(11):1182-9 16239589 Mol Biol Cell. 2006 Jan;17(1):25-31 16221891 Circ Res. 2006 Feb 3;98(2):254-61 16373599 Cell. 2006 Feb 24;124(4):783-801 16497588 J Biol Chem. 2006 Aug 4;281(31):22118-30 16735506 Blood. 2006 Nov 1;108(9):2906-13 16849637 J Biol Chem. 2006 Nov 10;281(45):34159-70 16980301 J Leukoc Biol. 2006 Dec;80(6):1214-21 16943386 Circulation. 2007 Feb 13;115(6):752-62 17261656 Thromb Haemost. 2007 May;97(5):738-47 17479184 J Clin Invest. 2001 Jan;107(1):3-6 11134170 Trends Cardiovasc Med. 2000 Feb;10(2):81-9 11150735 J Biol Chem. 2001 Jun 1;276(22):18953-9 11259422 Genes Dev. 2001 Sep 15;15(18):2321-42 11562344 Nature. 2001 Nov 15;414(6861):308-13 11713530 Arterioscler Thromb Vasc Biol. 2000 Nov;20(11):E83-8 11073859 Mol Cell. 2004 Mar 26;13(6):853-65 15053878 Mol Cell. 2004 May 7;14(3):303-17 15125834 Proc Natl Acad Sci U S A. 2004 Jun 8;101(23):8603-7 15173580 Med Sci Monit. 2004 Apr;10(4):RA89-98 15039660 Biochem J. 2004 Sep 1;382(Pt 2):393-409 15214841 Cancer Cell. 2004 Sep;6(3):203-8 15380510 Cancer Cell. 2004 Sep;6(3):297-305 15380520 Genes Dev. 1993 Nov;7(11):2064-70 8224838 Mol Cell Biol. 1997 Jul;17(7):4015-23 9199336 Cell. 1997 Sep 19;90(6):1051-60 9323133 J Biol Chem. 1997 Dec 19;272(51):32482-8 9405459 Nature. 2001 Nov 15;414(6861):313-7 11713531 J Cell Sci. 2002 Feb 1;115(Pt 3):455-65 11861753 Prog Neurobiol. 2002 Feb;66(2):61-79 11900882 J Biol Chem. 2002 Mar 29;277(13):10842-51 11801607 Cell. 2002 Apr;109 Suppl:S81-96 11983155 Nat Rev Cancer. 2002 Apr;2(4):301-10 12001991 Hypertension. 2002 Jun;39(6):1058-63 12052842 Clin Microbiol Rev. 2002 Jul;15(3):414-29 12097249 Breast Cancer Res Treat. 2002 Jun;73(3):237-43 12160329 Nat Rev Immunol. 2002 Oct;2(10):725-34 12360211 Nat Med. 2003 Mar;9(3):315-21 12592402 Trends Pharmacol Sci. 2003 Dec;24(12):626-33 14654303 Proc Natl Acad Sci U S A. 2004 Jan 6;101(1):192-7 14691254 Front Biosci. 2004 May 1;9:1201-17 14977537 J Cell Biol. 1998 May 18;141(4):1083-93 9585425 Annu Rev Biochem. 1998;67:653-92 9759500 Gut. 1998 Dec;43(6):856-60 9824616 Mol Cell Biol. 2004 Dec;24(23):10169-79 15542828 Cancer Biol Ther. 2004 Oct;3(10):1007-17 15467434 18093988 2008 08 29 2016 11 24

0008-6363 78 2 2008 May 01 Cardiovasc. Res. Exercise promotes angiogenesis and improves beta-adrenergic receptor signalling in the post-ischaemic failing rat heart. 385-94 We investigated whether exercise training could promote angiogenesis and improve blood perfusion and left ventricular (LV) remodelling of the post-myocardial infarction (MI) failing heart. We also explored the contribution of ameliorated beta-adrenergic receptor signalling and function on the overall improvement of cardiac contractility reserve induced by exercise. Adult Wistar male rats were randomly assigned to one of four experimental groups. Sham-operated and post-MI heart failure (HF) rats were housed under sedentary conditions or assigned to 10-weeks of a treadmill exercise protocol. At 4 weeks after MI, sedentary HF rats showed LV eccentric hypertrophy, marked increase of LV diameters associated with severely impaired fractional shortening (14 +/- 5%), increased LV end diastolic pressure (20.9 +/- 2.6 mmHg), and pulmonary congestion. In addition, cardiac contractile responses to adrenergic stimulation were significantly blunted. In trained HF rats, exercise was able to (i) reactivate the cardiac vascular endothelial growth factor pathway with a concurrent enhancement of myocardial angiogenesis, (ii) significantly increase myocardial perfusion and coronary reserve, (iii) reduce cardiac diameters, and (iv) improve LV contractility in response to adrenergic stimulation. This latter finding was also associated with a significant improvement of cardiac beta-adrenergic receptor downregulation and desensitization. Our data indicate that exercise favourably affects angiogenesis and improves LV remodelling and contractility reserve in a rat model of severe chronic HF. Leosco Dario D Cattedra di Geriatria, Dipartimento di Medicina Clinica, Scienze Cardiovascolari ed Immunologiche, Università Federico II, Via Pansini 5, 80131 Napoli, Italy. dleosco@unina.it Rengo Giuseppe G Iaccarino Guido G Golino Luca L Marchese Massimo M Fortunato Francesca F Zincarelli Carmela C Sanzari Emma E Ciccarelli Michele M Galasso Gennaro G Altobelli Giovanna Giuseppina GG Conti Valeria V Matrone Gianfranco G Cimini Vincenzo V Ferrara Nicola N Filippelli Amelia A Koch Walter J WJ Rengo Franco F eng Journal Article Research Support, Non-U.S. Gov't 2007 12 18

England Cardiovasc Res 0077427 0008-6363 0 Adrenergic beta-Agonists 0 Receptors, Adrenergic, beta 0 Vascular Endothelial Growth Factor A EC 1.14.13.39 Nitric Oxide Synthase Type II EC 1.14.13.39 Nitric Oxide Synthase Type III EC 1.14.13.39 Nos3 protein, rat EC 2.7.11.1 Proto-Oncogene Proteins c-akt L628TT009W Isoproterenol IM Adrenergic beta-Agonists pharmacology Animals Coronary Circulation Coronary Vessels drug effects metabolism physiopathology Disease Models, Animal Dose-Response Relationship, Drug Heart Failure diagnostic imaging etiology metabolism physiopathology Isoproterenol pharmacology Male Myocardial Contraction Myocardial Infarction complications diagnostic imaging metabolism physiopathology Myocardium enzymology metabolism pathology Neovascularization, Physiologic drug effects Nitric Oxide Synthase Type II metabolism Nitric Oxide Synthase Type III Physical Exertion Proto-Oncogene Proteins c-akt metabolism Rats Rats, Wistar Receptors, Adrenergic, beta drug effects metabolism Signal Transduction drug effects Time Factors Ultrasonography Vascular Endothelial Growth Factor A metabolism Ventricular Function, Left Ventricular Remodeling 2007 12 21 9 0 2008 8 30 9 0 2007 12 21 9 0 ppublish 18093988 cvm109 10.1093/cvr/cvm109 18084315 2008 05 15 2018 11 13

0007-1188 153 5 2008 Mar Br. J. Pharmacol. Endothelial alpha1-adrenoceptors regulate neo-angiogenesis. 936-46 Intact endothelium plays a pivotal role in post-ischaemic angiogenesis. It is a phenomenon finely tuned by activation and inhibition of several endothelial receptors. The presence of alpha(1)-adrenoceptors on the endothelium suggests that these receptors may participate in regenerative phenomena by regulating the responses of endothelial cells involved in neo-angiogenesis. We evaluated the expression of the subtypes of the alpha(1)-adrenoceptor in isolated endothelial cells harvested from Wistar-Kyoto (WKY) rats. We explored the possibility these alpha(1)-adrenoceptors may influence the pro-angiogenic phenotype of endothelial cells in vitro. In vivo, we used a model of hindlimb ischaemia in WKY rats, to assess the effects of alpha(1) adrenoceptor agonist or antagonist on angiogenesis in the ischaemic hindlimb by laser Doppler blood flow measurements, digital angiographies, hindlimb perfusion with dyed beads and histological evaluation. In vitro, pharmacological antagonism of alpha(1)-adrenoceptors in endothelial cells from WKY rats by doxazosin enhanced, while stimulation of these adrenoceptors with phenylephrine, inhibited endothelial cell proliferation and DNA synthesis, ERK and retinoblastoma protein (Rb) phosphorylation, cell migration and tubule formation. In vivo, we found increased alpha(1)-adrenoceptor density in the ischaemic hindlimb, compared to non-ischaemic hindlimb, suggesting an enhanced alpha(1)-adrenoceptor tone in the ischaemic tissue. Treatment with doxazosin (0.06 mg kg(-1) day(-1) for 14 days) did not alter systemic blood pressure but enhanced neo-angiogenesis in the ischaemic hindlimb, as measured by all our assays. Our findings support the hypothesis that the alpha(1)-adrenoceptors in endothelial cells provide a negative regulation of angiogenesis. Ciccarelli M M Division of Internal Medicine, Department of Clinical Medicine & Cardiovascular Sciences, Federico II University of Naples, Naples, Italy. Santulli G G Campanile A A Galasso G G Cervèro P P Altobelli G G GG Cimini V V Pastore L L Piscione F F Trimarco B B Iaccarino G G eng Journal Article 2007 12 17

England Br J Pharmacol 7502536 0007-1188 0 Adrenergic alpha-Agonists 0 Adrenergic alpha-Antagonists 0 Receptors, Adrenergic, alpha-1 1WS297W6MV Phenylephrine NW1291F1W8 Doxazosin IM Adrenergic alpha-Agonists pharmacology Adrenergic alpha-Antagonists pharmacology Animals Blood Pressure drug effects Cell Proliferation drug effects Doxazosin pharmacology Endothelial Cells metabolism Endothelium, Vascular cytology metabolism Gene Expression Hindlimb blood supply pathology In Vitro Techniques Ischemia physiopathology Neovascularization, Physiologic Phenylephrine pharmacology Rats Rats, Inbred WKY Receptors, Adrenergic, alpha-1 metabolism 2007 12 18 9 0 2008 5 16 9 0 2007 12 18 9 0 ppublish 18084315 0707637 10.1038/sj.bjp.0707637 PMC2267280 Nat Med. 2000 Apr;6(4):389-95 10742145 Am J Physiol Heart Circ Physiol. 2003 May;284(5):H1737-43 12679329 Pharmacol Rev. 2001 Jun;53(2):319-56 11356987 Am J Physiol Heart Circ Physiol. 2001 Aug;281(2):H873-81 11454593 Hypertension. 2001 Jul;38(1):136-41 11463774 J Am Coll Cardiol. 2001 Aug;38(2):534-40 11499749 Hypertension. 2001 Aug;38(2):255-60 11509486 J Clin Invest. 2003 Jun;111(12):1853-62 12813021 Circulation. 2004 Jun 1;109(21):2587-93 15136501 Cell Signal. 2004 Nov;16(11):1273-81 15337526 Nature. 1984 Feb 16-22;307(5952):648-9 6537993 Circ Res. 1986 Aug;59(2):163-70 2427248 Cardiovasc Res. 1989 Nov;23(11):913-20 2611800 J Clin Invest. 1994 Feb;93(2):662-70 7509344 Circ Res. 1995 Apr;76(4):544-50 7534658 Circulation. 1996 Mar 1;93(5):879-88 8598078 Am J Physiol. 1996 Aug;271(2 Pt 2):H752-9 8770119 Cell Signal. 1996 Aug;8(5):323-33 8911680 Cardiovasc Res. 1997 Mar;33(3):666-70 9093537 Clin Sci (Lond). 1997 May;92(5):453-4 9176017 Proc Natl Acad Sci U S A. 1997 Aug 19;94(17):9487-92 9256509 Hypertension. 1997 Nov;30(5):1128-34 9369266 Science. 1998 Apr 24;280(5363):574-7 9554846 J Clin Invest. 1998 Jun 1;101(11):2567-78 9616228 Cell Tissue Res. 1998 Aug;293(2):293-303 9662652 Microcirculation. 1998;5(1):7-23 9702718 Eur J Vasc Endovasc Surg. 1998 Jul;16(1):71-7 9715720 Circulation. 1998 Oct 27;98(17):1783-9 9788834 Mol Pharmacol. 1998 Nov;54(5):755-60 9804610 J Hypertens. 1998 Nov;16(11):1563-72 9856355 Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):3945-50 10097143 Oncogene. 2005 Apr 18;24(17):2909-15 15838524 Circ Res. 2005 Nov 25;97(11):1182-9 16239589 Circ Res. 2006 Feb 3;98(2):254-61 16373599 J Clin Invest. 2006 Apr;116(4):875-7 16585959 J Hypertens. 2006 May;24(5):861-5 16612247 J Biol Chem. 2006 Aug 11;281(32):22855-64 16774925 Cell Signal. 2006 Oct;18(10):1655-63 16517124 J Hypertens. 2007 Mar;25(3):551-6 17278970 Cell Signal. 2007 Sep;19(9):1949-55 17629454 Cardiovasc Res. 2007 Dec 1;76(3):453-64 17698050 Circ Res. 2001 Oct 12;89(8):645-7 11597985 Cancer Res. 2002 Jan 15;62(2):597-602 11809715 Am J Physiol Cell Physiol. 2002 May;282(5):C947-70 11940508 Circulation. 2002 May 7;105(18):2133-5 11994243 Circulation. 2002 May 28;105(21):2497-503 12034656 Circulation. 2002 Jul 16;106(3):349-55 12119252 Med Res Rev. 2003 Mar;23(2):117-45 12500286 J Biol Chem. 2003 Mar 7;278(10):8693-705 12471020 Biochem Biophys Res Commun. 2001 Mar 9;281(4):1019-23 11237765 17522350 2007 07 19 2019 05 13

1079-5006 62 5 2007 May J. Gerontol. A Biol. Sci. Med. Sci. Prior exercise improves age-dependent vascular endothelial growth factor downregulation and angiogenesis responses to hind-limb ischemia in old rats. 471-80 Downregulation of hypoxia-inducible factor 1 (HIF-1) and vascular endothelial growth factor (VEGF) are shown to be involved in age-dependent impairment of angiogenesis. In this study, we explore whether prior exercise is able to affect these molecular patterns favorably and to enhance neoangiogenesis in old Wistar rats with hind-limb ischemia. At day 7 after surgery, HIF-1alpha and VEGF expression increased in the ischemic muscle of trained animals. Exercise increased capillary density and limb perfusion as revealed by histologic, angiographic, and dyed bead techniques. Furthermore, exercise capacity and limb trophism have significantly improved in trained aged rats. In these animals, the reduction of VEGF serum levels has reflected the comprehensive improvement in local ischemia evoked by exercise. In conclusion, prior exercise represents a valid tool to counteract age-related molecular alterations resulting in impaired angiogenesis in response to ischemia. Leosco Dario D Dipartimento di Medicina Clinica, Scienze Cardiovascolari ed Immunologiche, Federico II University, Via Pansini 5, Edificio 2, 80131 Naples, Italy. dleosco@unina.it Rengo Giuseppe G Iaccarino Guido G Sanzari Emma E Golino Luca L De Lisa Gabriella G Zincarelli Carmela C Fortunato Francesca F Ciccarelli Michele M Cimini Vincenzo V Altobelli Giovanna Giuseppina GG Piscione Federico F Galasso Gennaro G Trimarco Bruno B Koch Walter J WJ Rengo Franco F eng Journal Article

United States J Gerontol A Biol Sci Med Sci 9502837 1079-5006 0 Hypoxia-Inducible Factor 1, alpha Subunit 0 Vascular Endothelial Growth Factor A AIM IM Aging physiology Analysis of Variance Animals Blood Flow Velocity Blotting, Western Down-Regulation physiology Hindlimb blood supply Hypoxia-Inducible Factor 1, alpha Subunit metabolism Ischemia Male Neovascularization, Physiologic physiology Physical Conditioning, Animal physiology Rats Rats, Wistar Vascular Endothelial Growth Factor A metabolism 2007 5 25 9 0 2007 7 20 9 0 2007 5 25 9 0 ppublish 17522350 62/5/471 10.1093/gerona/62.5.471 17188660 2007 03 30 2013 11 21

0006-8993 1132 1 2007 Feb 09 Brain Res. Calretinin distribution in the octopus brain: an immunohistochemical and in situ hybridization histochemical analysis. 71-7 The distribution of calretinin containing neurons examined by in situ hybridization mapping was compared with that obtained by immunocytochemistry in the brain of octopus. Results revealed a close correspondence between the two types of investigations. Western blot analysis disclosed a 29 kDa protein immunostained with anti-calretinin antibody. Calretinin containing neurons were localized mainly in the cortex of octopus lobes, including the vertical, frontal, basal, buccal, palliovisceral, pedal and branchial, with variations of staining intensity and density of immunoreactive cells. The amacrine cells surrounding calretinin containing neuronal bodies of the cortex were also labeled unlike the glial cells. The close correspondence of blotting analysis, immunocytochemistry and in situ hybridization indicates with no doubt that calretinin, like other calcium-binding proteins previously studied, is also present in the nervous system of cephalopods. Furthermore, although recent findings localize calretinin also in endocrine glands, the presence of this calcium-binding protein in the brain of octopus indicates that calretinin appeared early in the phylogeny as a neuronal protein already in invertebrates. Altobelli Giovanna G GG Department of Biomorphological and Functional Sciences, Federico II University of Naples, Via Pansini 5, 80131 Napoli, Italy. Cimini Vincenzo V eng Comparative Study Journal Article Research Support, Non-U.S. Gov't 2006 12 26

Netherlands Brain Res 0045503 0006-8993 0 Calbindin 2 0 RNA, Messenger 0 S100 Calcium Binding Protein G SY7Q814VUP Calcium IM Amacrine Cells cytology metabolism Animals Brain anatomy & histology metabolism Brain Mapping Calbindin 2 Calcium metabolism Endocrine System cytology metabolism Evolution, Molecular Ganglia, Invertebrate anatomy & histology metabolism Immunohistochemistry In Situ Hybridization Neurons metabolism Octopodiformes anatomy & histology metabolism Phylogeny RNA, Messenger metabolism S100 Calcium Binding Protein G genetics metabolism 2006 08 11 2006 11 09 2006 11 13 2006 12 26 9 0 2007 3 31 9 0 2006 12 26 9 0 ppublish 17188660 S0006-8993(06)03339-7 10.1016/j.brainres.2006.11.056 16239589 2005 12 22 2017 09 22

1524-4571 97 11 2005 Nov 25 Circ. Res. Ischemic neoangiogenesis enhanced by beta2-adrenergic receptor overexpression: a novel role for the endothelial adrenergic system. 1182-9 Beta2-adrenergic receptors (beta2ARs) are widely expressed, although their physiological relevance in many tissues is not yet fully understood. In vascular endothelial cells, they regulate NO release and vessel tone. Here we provide novel evidence that beta2ARs can regulate neoangiogenesis in response to chronic ischemia. We used in vivo adenoviral-mediated gene transfer of the human beta2AR to the endothelium of the rat femoral artery and increased beta2AR signaling resulting in ameliorated angiographic blood flow and hindlimb perfusion after chronic ischemia. Histological analysis confirmed that beta2AR overexpression also produced benefits on capillary density. The same maneuver partially rescued impaired angiogenesis in spontaneously hypertensive rats (SHR), whereas gene delivery of the G-protein-coupling defective mutant Ile164 beta2AR failed to provide ameliorations. Stimulation of endogenous and overexpressed beta2AR on endothelial cells in vitro was found to regulate cell number by inducing proliferation and [3H]-thymidine incorporation through means of extracellular receptor-activated kinase and vascular endothelial growth factor. The beta2AR also has novel effects on endothelial cell number through stimulation of proapoptosis and antiapoptosis pathways involving p38 mitogen-activated protein kinase and PI3-kinase/Akt activation. Therefore, beta2ARs play a critical role in endothelial cell proliferation and function including revascularization, suggesting a novel and physiologically relevant role in neoangiogenesis in response to ischemia. Iaccarino Guido G Dipartimento di Medicina Clinica e Scienze Cardiovascolari ed Immunologiche, Università Federico II, Naples, Italy. guiaccar@unina.it Ciccarelli Michele M Sorriento Daniela D Galasso Gennaro G Campanile Alfonso A Santulli Gaetano G Cipolletta Ersilia E Cerullo Vincenzo V Cimini Vincenzo V Altobelli Giovanna Giuseppina GG Piscione Federico F Priante Ornella O Pastore Lucio L Chiariello Massimo M Salvatore Francesco F Koch Walter J WJ Trimarco Bruno B eng GGP04039 Telethon Italy R01 HL65360 HL NHLBI NIH HHS United States Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't 2005 10 20

United States Circ Res 0047103 0009-7330 0 Receptors, Adrenergic, beta-2 EC 2.7.11.24 Extracellular Signal-Regulated MAP Kinases EC 2.7.11.24 p38 Mitogen-Activated Protein Kinases IM Animals Apoptosis Cell Proliferation Cells, Cultured Endothelial Cells pathology physiology Extracellular Signal-Regulated MAP Kinases physiology Genetic Therapy Humans Hypertension physiopathology Ischemia physiopathology Neovascularization, Physiologic Rats Rats, Inbred SHR Rats, Inbred WKY Receptors, Adrenergic, beta-2 analysis genetics physiology Signal Transduction p38 Mitogen-Activated Protein Kinases physiology 2005 10 22 9 0 2005 12 24 9 0 2005 10 22 9 0 ppublish 16239589 01.RES.0000191541.06788.bb 10.1161/01.RES.0000191541.06788.bb 16012461 2005 08 04 2012 10 03

0741-5214 42 1 2005 Jul J. Vasc. Surg. Thoracic outlet syndrome: pattern of clinical success after operative decompression. 122-8 To evaluate the pattern of clinical results in patients with neurogenic thoracic outlet syndrome (N-TOS) after operative decompression and longitudinal follow-up. From May 1994 to December 2002, 254 operative sides in 185 patients with N-TOS were treated by the same operative protocol: (1) transaxillary first rib resection and the lower part of scalenectomy for the primary procedure with or without (2) the subsequent upper part of scalenectomy with supraclavicular approach for patients with persistent or recurrent symptoms. This retrospective cohort study included 38 men and 147 women with an age range of 19 to 80 years (mean, 40 years). Evaluated were primary success, defined as uninterrupted success with no procedure performed, and secondary success, defined as success maintained by the secondary operation after the primary failure. Success was defined as > or =50% symptomatic improvement judged by the patient using a 10-point scale, returning to preoperational work status, or both. Follow-up was 2 to 76 months (mean, 25 months). Eighty sides underwent a secondary operation for the primary clinical failure. No technical failures and no deaths occurred < o =30 days after the operations. The complication rate was 4% (13/334) and consisted of 7 pneumothoraxes, 3 subclavian vein injuries, 1 nerve injury, 1 internal mammary artery injury, and 1 suture granuloma. Of 254 operative sides, the primary and secondary success was 46% (118/254) and 64% (163/254). Most the primary failures (90%, 122/136) and the secondary failures (66%, 23/35) occurred < or =18 months after the respective operation. The long-term results of operations for TOS in this study were much worse than those initially achieved, and most of the primary and secondary failures occurred < or =12 months of the respective operations. A minimum of 18-month follow-up on patients and standardized definition of the outcomes are necessary to determine the true effectiveness and outcome of operative treatment of N-TOS. Altobelli Grant G GG Gonda (Goldschmied) Vascular Center, University of California at Los Angeles, 90095, USA. Kudo Toshifumi T Haas Bradley T BT Chandra Fiona A FA Moy Jennifer L JL Ahn Samuel S SS eng Journal Article

United States J Vasc Surg 8407742 0741-5214 IM Algorithms Decompression, Surgical Humans Life Tables Reoperation Retrospective Studies Thoracic Outlet Syndrome surgery Treatment Outcome 2005 7 14 9 0 2005 8 5 9 0 2005 7 14 9 0 ppublish 16012461 S0741521405004672 10.1016/j.jvs.2005.03.029