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      Non-Bone Marrow Origin of Neointimal Smooth Muscle Cells in Experimental In-Stent Restenosis in Rats

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          Abstract

          Objective: To determine the contribution of bone marrow (BM)-derived cells in in-stent restenosis (ISR) and transplant arteriosclerosis (TA). Methods: Non-transgenic rats WT F344<sup>TG</sup> (n = 3) received stent implantation 6 weeks after lethal total body irradiation and suppletion with bone marrow from a R26-hPAP transgenic rat. After 4 weeks the abdominal aortas were harvested, the stent was quickly removed, the abdominal aorta was snap-frozen in liquid nitrogen and 5 µm cryosections for stainings were cut. Additionally, DA aortic allografts were transplanted into WT F344<sup>TG</sup> (n = 3) and R26-hPAP<sup>WT</sup> (n = 3) BM-chimeric recipients. Immunohistochemistry (hPAP staining) and immunofluorescence (hPAP, α-SMA and OX1) was performed on all sections. Results: Few hPAP-positive cells were observed in the neointima. Double stainings of hPAP-positive areas showed no α-SMA colocalization; OX-1 did show colocalization. Conclusions: Non-BM-derived cells are the predominant source of neointimal cells in ISR and TA. Vascular wall-derived progenitor cells may rather be the source of SMCs that contribute to ISR and TA, which may have implications for our quest for new therapeutic targets to treat these vasculopathies.

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          Most cited references 21

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          Effects of intravenous fluid restriction on postoperative complications: comparison of two perioperative fluid regimens: a randomized assessor-blinded multicenter trial.

          To investigate the effect of a restricted intravenous fluid regimen versus a standard regimen on complications after colorectal resection. Current fluid administration in major surgery causes a weight increase of 3-6 kg. Complications after colorectal surgery are reported in up to 68% of patients. Associations between postoperative weight gain and poor survival as well as fluid overload and complications have been shown. We did a randomized observer-blinded multicenter trial. After informed consent was obtained, 172 patients were allocated to either a restricted or a standard intraoperative and postoperative intravenous fluid regimen. The restricted regimen aimed at maintaining preoperative body weight; the standard regimen resembled everyday practice. The primary outcome measures were complications; the secondary measures were death and adverse effects. The restricted intravenous fluid regimen significantly reduced postoperative complications both by intention-to-treat (33% versus 51%, P = 0.013) and per-protocol (30% versus 56%, P = 0.003) analyses. The numbers of both cardiopulmonary (7% versus 24%, P = 0.007) and tissue-healing complications (16% versus 31%, P = 0.04) were significantly reduced. No patients died in the restricted group compared with 4 deaths in the standard group (0% versus 4.7%, P = 0.12). No harmful adverse effects were observed. The restricted perioperative intravenous fluid regimen aiming at unchanged body weight reduces complications after elective colorectal resection.
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            Pharmacokinetic issues for antibiotics in the critically ill patient.

            To discuss the altered pharmacokinetic properties of selected antibiotics in critically ill patients and to develop basic dose adjustment principles for this patient population. PubMed, EMBASE, and the Cochrane-Controlled Trial Register. Relevant papers that reported pharmacokinetics of selected antibiotic classes in critically ill patients and antibiotic pharmacodynamic properties were reviewed. Antibiotics and/or antibiotic classes reviewed included aminoglycosides, beta-lactams (including carbapenems), glycopeptides, fluoroquinolones, tigecycline, linezolid, lincosamides, and colistin. Antibiotics can be broadly categorized according to their solubility characteristics which can, in turn, help describe possible altered pharmacokinetics that can be caused by the pathophysiological changes common to critical illness. Hydrophilic antibiotics (e.g., aminoglycosides, beta-lactams, glycopeptides, and colistin) are mostly affected with the pathphysiological changes observed in critically ill patients with increased volumes of distribution and altered drug clearance (related to changes in creatinine clearance). Lipophilic antibiotics (e.g., fluoroquinolones, macrolides, tigecycline, and lincosamides) have lesser volume of distribution alterations, but may develop altered drug clearances. Using antibiotic pharmacodynamic bacterial kill characteristics, altered dosing regimens can be devised that also account for such pharmacokinetic changes. Knowledge of antibiotic pharmacodynamic properties and the potential altered antibiotic pharmacokinetics in critically ill patients can allow the intensivist to develop individualized dosing regimens. Specifically, for renally cleared drugs, measured creatinine clearance can be used to drive many dose adjustments. Maximizing clinical outcomes and minimizing antibiotic resistance using individualized doses may be best achieved with therapeutic drug monitoring.
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              Vascular wall resident progenitor cells: a source for postnatal vasculogenesis.

              Here, we report the existence of endothelial precursor (EPC) and stem cells in a distinct zone of the vascular wall that are capable to differentiate into mature endothelial cells, hematopoietic and local immune cells, such as macrophages. This zone has been identified to be localized between smooth muscle and adventitial layer of human adult vascular wall. It predominantly contains CD34-positive (+) but CD31-negative (-) cells, which also express VEGFR2 and TIE2. Only few cells in this zone of the vascular wall are positive for CD45. In a ring assay using the fragments of human internal thoracic artery (HITA), we show here that the CD34+ cells of the HITA-wall form capillary sprouts ex vivo and are apparently recruited for capillary formation by tumor cells. New vessels formed by these vascular wall resident EPCs express markers for angiogenically activated endothelial cells, such as CEACAM1, and also for mature endothelial cells, such as VE-cadherin or occludin. Vascular wall areas containing EPCs are found in large and middle sized arteries and veins of all organs studied here. These data suggest the existence of a ;vasculogenic zone' in the wall of adult human blood vessels, which may serve as a source for progenitor cells for postnatal vasculogenesis, contributing to tumor vascularization and local immune response.
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                Author and article information

                Journal
                JVR
                J Vasc Res
                10.1159/issn.1018-1172
                Journal of Vascular Research
                S. Karger AG
                1018-1172
                1423-0135
                2008
                October 2008
                23 April 2008
                : 45
                : 6
                : 493-502
                Affiliations
                Departments of aClinical Pharmacology, bCardiology, and cCell Biology, Immunology Section, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
                Article
                127440 J Vasc Res 2008;45:493–502
                10.1159/000127440
                18434748
                © 2008 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 7, References: 31, Pages: 10
                Categories
                Research Paper

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