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Isolated limb perfusion

Puneet Kaur Randhawa, Amteshwar Singh Jaggi
Remote ischemic preconditioning (RIPC) treatment strategy is a breakthrough in the field of cardiovascular pharmacology as it has the potential to attenuate myocardial ischemia-reperfusion injury. However, the underlying intracellular pathways have not been widely explored. The present study intends to explore the possible role of TRPV1 channels in mediating remote hind limb preconditioning-induced cardioprotection. Remote hind limb preconditioning stimulus (4 cycles in succession) was delivered by tying the blood pressure cuff at the inguinal level of the rat...
October 17, 2016: Naunyn-Schmiedeberg's Archives of Pharmacology
W Kyle Mitchell, Bethan E Phillips, Daniel J Wilkinson, John P Williams, Debbie Rankin, Jonathan N Lund, Kenneth Smith, Philip J Atherton
Postprandial limb blood flow and skeletal muscle microvascular perfusion reduce with aging. Here we tested the impact of providing bolus essential amino acids (EAA) in the presence and absence of the nitric oxide precursor, l-Arginine (ARG), upon skeletal muscle blood flow and anabolism in older men. Healthy young (YOUNG: 19.7 ± 0.5 y, N = 8) and older men (OLD, 70 ± 0.8 y, N = 8) received 15 g EAA or (older only) 15 g EAA +3 g ARG (OLD-ARG, 69.2 ± 1.2 y, N = 8). We quantified responses in muscle protein synthesis (MPS; incorporation of (13)C phenylalanine into myofibrillar proteins), leg and muscle microvascular blood flow (Doppler/contrast enhanced ultrasound (CEUS)) and insulin/EAA in response to EEA ± ARG...
October 6, 2016: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
J Trnka, M Špaček, V Šírová, P Mitáš, G Hodková, J Kubinyi, R Špunda, J Lindner
BACKGROUND: Hyperthermic isolated limb perfusion is used to treat irresectable extremity malignancies. It is based on the following principle - the perfusion of the extremity is isolated from systemic circulation and connected to an extra-corporal circuit via which a very high concentration of a chemotherapeutic agent is administered into the blood compartment of the extremity. In some cases, treatment efficiency can be improved using tasonermin (a TNF-α agent). By itself, tasonermin can cause severe health complications in patients if leakage into systemic circulation results in a level that exceeds the maximally tolerated dose...
2016: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
Alison Harvey, Isabelle Kilcoyne, Barbara A Byrne, Jorge Nieto
OBJECTIVE: To compare synovial concentrations of amikacin following intravenous regional limb perfusion (IVRLP) with two different doses, and to compare their ability to reach target concentrations for bacterial isolates from common orthopedic conditions. STUDY DESIGN: Randomized crossover experiment. ANIMALS: Six adult horses. METHODS: Horses received IVRLP with 2 and 3 g of amikacin in the cephalic vein of alternate limbs (20 minutes tourniquet application and ≥14 days washout period)...
September 29, 2016: Veterinary Surgery: VS
Christin Boldt, Tom Roeschel, Nina Himmerkus, Allein Plain, Markus Bleich, Robert Labes, Maximilian Blum, Hans Krause, Ahmed Magheli, Torsten Giesecke, Kerim Mutig, Michael Rothe, Steven M Weldon, Duska Dragun, Wolf-Hagen Schunck, Sebastian Bachmann, Alexander Paliege
Activation of the thick ascending limb (TAL) Na+-K+-2Cl--cotransporter (NKCC2) by the antidiuretic hormone arginine-vasopressin (AVP) is an essential mechanism of renal urine concentration and contributes to extracellular fluid and electrolyte homeostasis. AVP effects in the kidney are modulated by locally and/or by systemically produced epoxyeicosatrienoic acid derivates (EET). The relation between AVP and EET metabolism has not been determined. Here we show that chronic treatment of AVP-deficient Brattleboro rats with the AVP V2 receptor analog desmopressin (dDAVP; 5ng/h, 3d) significantly lowered renal EET levels (-56 ± 3% for 5,6-EET, -50 ± 3...
September 28, 2016: American Journal of Physiology. Renal Physiology
Minhyung Kim, Nickolay Neznanov, Chandler D Wilfong, Daria I Fleyshman, Andrei A Purmal, Gary Haderski, Patricia Stanhope-Baker, Catherine Burkhart, Katerina V Gurova, Andrei V Gudkov, Joseph J Skitzki
Isolated limb perfusion (ILP) with the chemotherapeutic agent melphalan is an effective treatment option for extremity in-transit melanoma, but is toxic and technically challenging to deliver locoregionally. CBL0137 is an experimental clinical drug with broad anticancer activity in animal models, owing to its ability to bind DNA in a non-genotoxic manner and inactivate the FACT chromatin modulator essential for tumor cell viability. Here we report that CBL0137 delivered by ILP in a murine melanoma model is as efficacious as melphalan, displaying antitumor activity at doses corresponding to only a fraction of the systemic MTD of CBL0137...
September 28, 2016: Cancer Research
Ana Rita S Pereira, Teresa F Mendes, Augusto Ministro, Mariana Teixeira, Mariana Filipe, Jorge M Santos, Rita N Bárcia, J Goyri-O'Neill, Fausto Pinto, Pedro E Cruz, Helder J Cruz, Susana Constantino Rosa Santos
BACKGROUND: Mesenchymal stem cells derived from human umbilical cord tissue, termed UCX®, have the potential to promote a full range of events leading to tissue regeneration and homeostasis. The main goal of this work was to investigate UCX® action in experimentally induced hindlimb ischemia (HLI). METHODS: UCX®, obtained by using a proprietary technology developed by ECBio (Amadora, Portugal), were delivered via intramuscular injection to C57BL/6 females after unilateral HLI induction...
September 29, 2016: Stem Cell Research & Therapy
Zhongjian Cheng, Venkata Garikipati, Emily Nickoloff, Chunlin Wang, David J Polhemus, Jibin Zhou, Cynthia Benedict, Mohsin Khan, Suresh K Verma, Joseph E Rabinowitz, David Lefer, Raj Kishore
BACKGROUND: -Bone marrow cell-based treatment for critical limb ischemia (CLI) in diabetic patients yielded a modest therapeutic effect due to cell dysfunction. Therefore, approaches that improve diabetic stem/progenitor cell functions may provide therapeutic benefits. Here, we tested the hypotheses that restoration of hydrogen sulfide (H2S) production in diabetic bone marrow cells (BMCs) improves their reparative capacities. METHODS: -Mouse BMCs were isolated by density-gradient centrifugation...
September 22, 2016: Circulation
Cunping Yin, Yuan Liang, Jian Zhang, Guangping Ruan, Zian Li, Rongqing Pang, Xinghua Pan
Hindlimb ischemia is still a clinical problem with high morbidity and mortality. Patients suffer from consequent rest pain, ulcers, cool limbs, and even amputation. Angiogenesis is a promising target for the treatment of ischemic limbs, providing extra blood for the ischemic region. In the present study, we investigated the role of umbilical cord-derived mesenchymal stem cells (UC-MSCs) in regulating angiogenesis and relieving hindlimb ischemia. UC-MSCs were isolated from the umbilical cord of tree shrews. Angiography results showed that UC-MSCs injection significantly promoted angiogenesis in tree shrews...
2016: Stem Cells International
Tania Tsatralis, Anisyah Ridiandries, Stacy Robertson, Laura Z Vanags, Yuen Ting Lam, Joanne T M Tan, Martin K C Ng, Christina A Bursill
BACKGROUND: The average population age is increasing and the incidence of age-related vascular complications is rising in parallel. Impaired wound healing and disordered ischemia-mediated angiogenesis are key contributors to age-impaired vascular complications that can lead to amputation. High-density lipoproteins (HDL) have vasculo-protective properties and augment ischemia-driven angiogenesis in young animals. We aimed to determine the effect of reconstituted HDL (rHDL) on aged mice in a murine wound healing model and the hindlimb ischemia (HLI) model...
2016: Lipids in Health and Disease
Jaume Padilla, Francisco I Ramirez-Perez, Javad Habibi, Brian Bostick, Annayya R Aroor, Melvin R Hayden, Guanghong Jia, Mona Garro, Vincent G DeMarco, Camila Manrique, Frank W Booth, Luis A Martinez-Lemus, James R Sowers
We recently showed that Western diet-induced obesity and insulin resistance promotes endothelial cortical stiffness in young female mice. Herein, we tested the hypothesis that regular aerobic exercise would attenuate the development of endothelial and whole artery stiffness in female Western diet-fed mice. Four-week-old C57BL/6 mice were randomized into sedentary (ie, caged confined, n=6) or regular exercise (ie, access to running wheels, n=7) conditions for 16 weeks. Exercise training improved glucose tolerance in the absence of changes in body weight and body composition...
November 2016: Hypertension
Michael J Zhang, Brian E Sansbury, Jason Hellmann, James F Baker, Luping Guo, Caitlin M Parmer, Joshua C Prenner, Daniel J Conklin, Aruni Bhatnagar, Mark A Creager, Matthew Spite
BACKGROUND: Resolvins are lipid mediators generated by leukocytes during the resolution phase of inflammation. They have been shown to regulate the transition from inflammation to tissue repair; however, it is unknown whether resolvins play a role in tissue revascularization following ischemia. METHODS: We used a murine model of hind limb ischemia (HLI), coupled with laser Doppler perfusion imaging, microcomputed tomography, and targeted mass spectrometry, to assess the role of resolvins in revascularization and inflammation resolution...
August 30, 2016: Circulation
Jack M J Pickard, Sean M Davidson, Derek J Hausenloy, Derek M Yellon
The cardioprotection afforded by remote ischaemic conditioning (RIC) is mediated via a complex mechanism involving sensory afferent nerves, the vagus nerve, and release of a humoral blood-borne factor. However, it is unknown whether release of the protective factor depends on vagal activation or occurs independently. This study aimed to evaluate the co-dependence of the neural and humoral pathways of RIC, focussing on the vagus nerve and intrinsic cardiac ganglia. In the first study, anesthetised rats received bilateral cervical vagotomy or sham-surgery immediately prior to RIC (4 × 5 min limb ischemia-reperfusion) or sham-RIC...
July 2016: Basic Research in Cardiology
Valerio Belgrano, Ilan Ben-Shabat, Peter Bergh, Roger Olofsson Bagge
BACKGROUND: Isolated limb perfusion (ILP) is an established and effective treatment for advanced melanoma and soft tissue sarcomas of the extremities with a high overall response rate. The aim of this study was to describe our experience of ILP for more rare types of tumours. METHODS: Patients with Merkel cell carcinoma (MCC) (n = 4), squamous cell carcinoma (SCC) (n = 2), B-cell lymphoma (n = 1), desmoid tumours (n = 3), pigmented villonodular synovitis (PVNS) (n = 1) and giant cell tumour (n = 1) were treated with ILP and analysed retrospectively...
September 2016: International Journal of Hyperthermia
Jocelyn Lippey, Rhiannon Bousounis, Cori Behrenbruch, Bartholomew McKay, John Spillane, Michael A Henderson, David Speakman, David E Gyorki
BACKGROUND AND OBJECTIVES: Patients with in-transit melanoma metastasis have longer median survival than patients with distant metastatic disease. Furthermore, local disease control is an important endpoint for symptom management. The treatment of unresectable loco-regional recurrence or in-transit disease has been historically managed with a combination of treatments including surgery, radiotherapy, isolated limb infusion or perfusion as well as systemic therapies. Intralesional PV-10 has been used at Peter MacCallum Cancer Centre since 2010, and the current report presents a retrospective analysis of patient outcomes, reporting the response rates, durability of responses, and observed toxicities...
September 2016: Journal of Surgical Oncology
Jens Jakob, Peter Hohenberger
The management of locally advanced extremity soft tissue sarcoma of the limbs is challenging, particularly for recurrent tumors and those adjacent to neurovascular bundles and joints. Typically, the tumors are large, below the fascia, and high-grade (T2b or stage III according to the American Joint Committee on Cancer) and thus require multimodal therapy. Treatment options must be tailored to patient and tumor characteristics. Isolated limb perfusion with recombinant human tumor necrosis factor α and melphalan (TNF-ILP) adds a therapeutic option to radiation therapy (RT) and systemic chemotherapy...
September 1, 2016: Cancer
Cornelius A Thiels, Alexandra B Gonzalez, Richard J Gray, James W Jakub
INTRODUCTION: Hyperthermic isolated limb perfusion (HILP) has an established role in the management of melanoma, but its role for Merkel cell carcinoma (MCC) is less well defined. METHODS: Retrospective review of our institutional experience with HILP for MCC was conducted (2009-2015). Literature search was performed through 04/2015 and 10 studies met inclusion criteria. RESULTS: Four patients underwent HILP for MCC at our institution. There were no major complications and complete response was achieved in all patients...
August 2016: Journal of Surgical Oncology
Michelle J Wilkinson, Henry G Smith, Timothy D Pencavel, David C Mansfield, Joan Kyula-Currie, Aadil A Khan, Gráinne McEntee, Victoria Roulstone, Andrew J Hayes, Kevin J Harrington
The management of locally advanced or recurrent extremity sarcoma often necessitates multimodal therapy to preserve a limb, of which isolated limb perfusion (ILP) is a key component. However, with standard chemotherapeutic agents used in ILP, the duration of response is limited. Novel agents or treatment combinations are urgently needed to improve outcomes. Previous work in an animal model has demonstrated the efficacy of oncolytic virotherapy when delivered by ILP and, in this study, we report further improvements from combining ILP-delivered oncolytic virotherapy with radiation and surgical resection...
September 15, 2016: International Journal of Cancer. Journal International du Cancer
Gianluca L Perrucci, Stefania Straino, Maria Corlianò, Alessandro Scopece, Monica Napolitano, Bradford C Berk, Federico Lombardi, Giulio Pompilio, Maurizio C Capogrossi, Patrizia Nigro
BACKGROUND: Critical limb ischemia (CLI) is a major health problem with no adequate treatment. Since CLI is characterized by insufficient tissue vascularization, efforts have focused on the discovery of novel angiogenic factors. Cyclophilin A (CyPA) is an immunophilin that has been shown to promote angiogenesis in vitro and to enhance bone marrow (BM) cell mobilization in vivo. However, its potential as an angiogenic factor in CLI is still unknown. Thus, this study aimed to evaluate whether CyPA might induce neo-angiogenesis in ischemic tissues...
June 1, 2016: International Journal of Cardiology
D Cecchin, A Negri, A C Frigo, F Bui, P Zucchetta, V Bodanza, M Gregianin, L G Campana, C R Rossi, M Rastrelli
INTRODUCTION: Hyperthermic isolated limb perfusion (HILP) can be performed as an alternative to amputation for soft tissue sarcomas and melanomas of the extremities. Melphalan and tumor necrosis factor-alpha are used at a dosage that depends on the volume of the limb. Regional tissue volume is traditionally measured for the purposes of HILP using water displacement volumetry (WDV). Although this technique is considered the gold standard, it is time-consuming and complicated to implement, especially in obese and elderly patients...
March 8, 2016: European Journal of Surgical Oncology
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