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      Call for Papers: Green Renal Replacement Therapy: Caring for the Environment

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      Physical Activity in Solid Organ Transplant Recipients: Preliminary Results of the Italian Project

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          Abstract

          Background/Aims: The role of physical activity in transplanted patients is often underestimated. We discuss the Italian National Transplant Centre experience, which started in 2008 studying transplanted patients involved in sports activities. The study was then developed through a model of cooperation between surgeons, sports physicians and exercise specialists. Methods: A multicentre study was realized in 120 transplanted patients of which 60 treated with supervised physical activity (three sessions/week of aerobic and strengthening exercises) and 60 controls. We present the results of the first 26 patients (16 males, 10 females; 47.8±10.0 years; 21 kidney, 5 liver transplanted; time from transplant 2.3±1.4 years) who completed 12 months of supervised physical activity. Results: Data showed an increase of peak aerobic power (t=4.535; P<0.01) and maximum workload (t=4.665; P<0.01) in the incremental cycling test. Maximum strength of knee extensors (t=2.933; P<0.05) and elbow flexors (t=2.450; P<0.05), and the power of lower limb (t=2.303; P<0.05) significantly increases. Health Related Quality of Life showed a significant improvement. Serum creatinine (1.4±0.5 vs 1.3±0.4 mg/dL) and proteinuria (0.10±0.14 vs 0.08±0.08 gr/dL) were stable. Conclusion: These preliminary results confirm the positive effects of supervised physical exercise. It can be considered as an input to promote other detailed exercise protocols.

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          Rapamycin administration in humans blocks the contraction-induced increase in skeletal muscle protein synthesis.

          Muscle protein synthesis and mTORC1 signalling are concurrently stimulated following muscle contraction in humans. In an effort to determine whether mTORC1 signalling is essential for regulating muscle protein synthesis in humans, we treated subjects with a potent mTORC1 inhibitor (rapamycin) prior to performing a series of high-intensity muscle contractions. Here we show that rapamycin treatment blocks the early (1-2 h) acute contraction-induced increase ( approximately 40%) in human muscle protein synthesis. In addition, several downstream components of the mTORC1 signalling pathway were also blunted or blocked by rapamycin. For instance, S6K1 phosphorylation (Thr421/Ser424) was increased post-exercise 6-fold in the control group while being unchanged with rapamycin treatment. Furthermore, eEF2 phosphorylation (Thr56) was reduced by approximately 25% post-exercise in the control group but phosphorylation following rapamycin treatment was unaltered, indicating that translation elongation was inhibited. Rapamycin administration prior to exercise also reduced the ability of raptor to associate with mTORC1 during post-exercise recovery. Surprisingly, rapamycin treatment prior to resistance exercise completely blocked the contraction-induced increase in the phosphorylation of ERK1/2 (Thr202/Tyr204) and blunted the increase in MNK1 (Thr197/202) phosphorylation. However, the phosphorylation of a known target of MNK1, eIF4E (Ser208), was similar in both groups (P > 0.05) which is consistent with the notion that rapamycin does not directly inhibit MAPK signalling. We conclude that mTORC1 signalling is, in part, playing a key role in regulating the contraction-induced stimulation of muscle protein synthesis in humans, while dual activation of mTORC1 and ERK1/2 stimulation may be required for full stimulation of human skeletal muscle protein synthesis.
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            Reduction in cardiovascular death after kidney transplantation.

            Cardiovascular (CVS) disease is the commonest cause of death after kidney transplantation. In the general population, CVS mortality has reduced significantly over the last two decades; however, this trend has not been specifically examined in the kidney transplant population. We studied all patients in Australia and New Zealand with a functioning kidney transplant between 1980 and 2007 and examined trends in the cause and timing of all 2195 deaths recorded after kidney transplantation in the Australia and New Zealand Dialysis and Transplant registry. Poisson regression was used to compare death rates over the time periods. CVS events were the commonest cause of death throughout all the time points examined; however, CVS death rates significantly decreased with an adjusted risk ratio of 0.61 (95% confidence interval, 0.38-0.96; P=0.034) for 2005 to 2007 era. In comparison, death rates due to malignancy have increased significantly over this period. Decreased CVS death rates have occurred despite increasing comorbidity at the time of transplantation. Factors associated with CVS death were older recipient age, preexisting CVS disease, and diabetes mellitus. There was a significantly lower CVS death rate in patients with a glomerular filtration rate >48 mL/min compared with those with poor renal function (risk ratio, 0.66; 95% confidence interval, 0.45-0.95; P=0.024). These trends suggest improvements in CVS risk management and outcomes in the kidney transplant population in Australia and New Zealand.
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              The Functional Role of Calcineurin in Hypertrophy, Regeneration, and Disorders of Skeletal Muscle

              Skeletal muscle uses calcium as a second messenger to respond and adapt to environmental stimuli. Elevations in intracellular calcium levels activate calcineurin, a serine/threonine phosphatase, resulting in the expression of a set of genes involved in the maintenance, growth, and remodeling of skeletal muscle. In this review, we discuss the effects of calcineurin activity on hypertrophy, regeneration, and disorders of skeletal muscle. Calcineurin is a potent regulator of muscle remodeling, enhancing the differentiation through upregulation of myogenin or MEF2A and downregulation of the Id1 family and myostatin. Foxo may also be a downstream candidate for a calcineurin signaling molecule during muscle regeneration. The strategy of controlling the amount of calcineurin may be effective for the treatment of muscular disorders such as DMD, UCMD, and LGMD. Activation of calcineurin produces muscular hypertrophy of the slow-twitch soleus muscle but not fast-twitch muscles.
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                Author and article information

                Journal
                KBR
                Kidney Blood Press Res
                10.1159/issn.1420-4096
                Kidney and Blood Pressure Research
                S. Karger AG
                978-3-318-02734-1
                1420-4096
                1423-0143
                2014
                August 2014
                29 July 2014
                : 39
                : 2-3
                : 220-227
                Affiliations
                aOperative Unit of Nephrology and Dialysis, Morgagni Pierantoni Hospital, Forlì; bNephrology, Dialysis, Renal Transplantation Unit, S. Orsola-Malpighi University Hospital, Bologna; cNo Profit Foundation for the Advancement of Organ and Tissue Transplantation (FITOT), Padova; dEducational and Research Department Isokinetic Medical Group, Bologna; eUOC of Sport Medicine, ULSS Company 9, Treviso; fItalian National Transplant Centre, Istituto Superiore di Sanità, Roma, Italy
                Article
                355800 Kidney Blood Press Res 2014;39:220-227
                10.1159/000355800
                25118112
                af36958a-8616-4dd3-9cee-64503dd98566
                © 2014 S. Karger AG, Basel

                Open Access License: This is an Open Access article licensed under the terms of the Creative Commons Attribution-NonCommercial 3.0 Unported license (CC BY-NC) ( http://www.karger.com/OA-license), applicable to the online version of the article only. Distribution permitted for non-commercial purposes only. 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.

                History
                : 11 April 2014
                Page count
                Pages: 8
                Categories
                Original Paper

                Cardiovascular Medicine,Nephrology
                Physical exercise,Muscle strength,Aerobic activity,Lifestyle,Cardio-vascular disease prevention,Kidney transplant,Liver transplant

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