Pleiotrophin-induced endothelial cell migration is regulated by xanthine oxidase-mediated generation of reactive oxygen species

Pleiotrophin (PTN) is a heparin-binding growth factor that induces cell migration through binding to its receptor protein tyrosine phosphatase beta/zeta (RPTPβ/ζ) and integrin alpha v beta 3 (ανβ3). In the present work, we studied the effect of PTN on the generation of reactive oxygen species (ROS) in human endothelial cells and the involvement of ROS in PTN-induced cell migration. Exogenous PTN significantly increased ROS levels in a concentration and time-dependent manner in both human endothelial and prostate cancer cells, while knockdown of endogenous PTN expression in prostate cancer cells significantly down-regulated ROS production. Suppression of RPTPβ/ζ through genetic and pharmacological approaches, or inhibition of c-src kinase activity abolished PTN-induced ROS generation. A synthetic peptide that blocks PTN–ανβ3 interaction abolished PTN-induced ROS generation, suggesting that ανβ3 is also involved. The latter was confirmed in CHO cells that do not express β3 or over-express wild-type β3 or mutant β3Y773F/Y785F. PTN increased ROS generation in cells expressing wild-type β3 but not in cells not expressing or expressing mutant β3. Phosphoinositide 3-kinase (PI3K) or Erk1/2 inhibition suppressed PTN-induced ROS production, suggesting that ROS production lays down-stream of PI3K or Erk1/2 activation by PTN. Finally, ROS scavenging and xanthine oxidase inhibition completely abolished both PTN-induced ROS generation and cell migration, while NADPH oxidase inhibition had no effect. Collectively, these data suggest that xanthine oxidase-mediated ROS production is required for PTN-induced cell migration through the cell membrane functional complex of ανβ3 and RPTPβ/ζ and activation of c-src, PI3K and ERK1/2 kinases

Electroneuromuscular stimulation in ICU patients as an additional measurement of conventional physiotherapy

Objective: We aimed to examine whether the application of transcutaneous electric neuromuscular stimulation sessions (TENMS) may reduce the incidence or severity of the critical illness myopathy (CIM) in intensive care unit (ICU) patients.Design: Prospective, open label, controlled, randomized clinical trial.Setting: University HospitalPatients: Patient inclusion criteria included mechanical ventilation and intensive care unit stay of >96 hrs, age>18.Interventions: Conventional physical therapy control group (CG) and application of TENMS in addition to conventional physiotherapy trial group (TENMSG) for 10 days.Myopathy was histologically assessed (needle biopsies in quadriceps muscles) on the 4th and 14th ICU day.Measurements and Main Results: Twenty-seven patients out of 68 (39.7%) presented myopathy on the 14th ICU day: eleven patients in TENMSG (grade + n=9, grade ++ n=1, grade +++ n=1) and 16 patients in CG (grade + n=13, grade ++ n=2, grade +++ n=1). Patients who presented progression from early grade + myopathy to more severe myopathy (grades ++ or +++) between the 4th and 14th day, had significantly lower BMI and experienced longer time periods (days) with inadequate nutrition compared to the rest of the patients (p<0.05). The 6 point Rankin scale which was assessed at 6 months sowed that the scores in TENMSG and CG were 3.18(1.8) mean (SD) and 3.8 (2.1) respectively (p=0.09). However, we estimated that the percentage of patients with score <4 (moderate disability or no symptoms) were significantly higher in TENMSG compared to CG (57% vs 40%, p=0.01).Conclusion: TENMS had no significant impact in myopathy in critical care patients of this study.Σκοπός: Σκοπός μας ήταν να εξετάσουμε εάν η εφαρμογή της ηλεκτρονευρομυϊκής διέγερσης (ΗΝΜΔ) μπορεί να μειώσει τη συχνότητα ή τη σοβαρότητα της μυοπάθειας των βαρέως πασχόντων που νοσηλεύονται σε Μονάδα Εντατικής Θεραπείας (ΜΕΘ).Μέθοδος – Ασθενείς: Πρόκειται για μια προοπτική, ανοιχτή, ελεγχόμενη, τυχαιοποιημένη κλινική δοκιμή που διεξήχθη στη ΜΕΘ του Πανεπιστημιακού Γενικού Νοσοκομείου Λάρισας. Στη μελέτη συμμετείχαν όλοι οι ασθενείς που ήταν σε μηχανική αναπνοή για τουλάχιστον 96 ώρες και άνω των 18 ετών.Παρεμβάσεις: Οι ασθενείς χωρίστηκαν σε δύο ομάδες, στην ομάδα ελέγχου όπου εφαρμοζόταν η συμβατική φυσικοθεραπεία και την ομάδα παρέμβασης όπου εφαρμοζόταν πλέον της συμβατικής φυσικοθεραπείας ΗΝΜΔ για 10 συνεχόμενες ημέρες. Η μυοπάθεια της κρίσιμης ασθένειας αξιολογήθηκε ιστολογικά (βιοψία μυός τετρακέφαλου άμφω) την 4η και 14η ημέρα νοσηλείας στη ΜΕΘ. Αποτελέσματα: Είκοσι επτά από τους 68 (39.7%) ασθενείς εμφάνισαν μυοπάθεια της κρίσιμης ασθένειας την 14η ημέρα νοσηλείας τους στη ΜΕΘ: 11 ασθενείς ήταν της ομάδας παρέμβασης (ΗΝΜΔ) (βαθμού + n=9, βαθμού ++ n=1, βαθμού +++ n=1) και 16 ασθενείς της ομάδας ελέγχου (βαθμού+ n=13, βαθμού ++ n=2, βαθμού +++ n=1). Οι ασθενείς που εμφάνισαν προοδευτική εξέλιξη της μυοπάθειας από την πρώιμη μυοπάθεια, βαθμού + σε μέτρια ++ ή και σοβαρότερη μυοπάθεια +++ μεταξύ της 4ης και της 14ης ημέρας είχαν σημαντικά χαμηλότερο δείκτη μάζας σώματος (ΔΜΣ) και για μεγαλύτερο χρονικό διάστημα (ημέρες) κατά τη νοσηλεία τους ήταν σε ανεπαρκή σίτιση εν συγκρίσει με το υπόλοιπο των ασθενών (p<0,05). Η τροποποιημένη κλίμακα βαθμονόμησης μυϊκής δύναμης Rankin scale score των 6 σημείων που αξιολογήθηκε 6 μήνες μετά την έξοδό τους από τη ΜΕΘ, έδειξε ότι στην ομάδα παρέμβασης (ΗΝΜΔ) και την ομάδα ελέγχου ήταν 3,18 (1,8) και 3,8 (2,1) αντίστοιχα (p = 0,09). Ωστόσο, εκτιμήσαμε ότι το ποσοστό των ασθενών με βαθμολογία <4 (μέτρια αναπηρία ή χωρίς συμπτώματα) ήταν σημαντικά υψηλότερο στην ομάδα παρέμβασης (ΗΝΜΔ) σε σύγκριση με την ομάδα ελέγχου (57% έναντι 40%, p = 0,01).Συμπέρασμα: Η ΗΝΜΔ δεν είχε σημαντική επίδραση στη μυοπάθεια των βαρέως πασχόντων της ΜΕΘ σε αυτή τη μελέτη

Receptor protein tyrosine phosphatase beta/zeta is a functional binding partner for vascular endothelial growth factor

Background: Receptor protein tyrosine phosphatase beta/zeta (RPTPβ/ζ) is a chondroitin sulphate (CS) transmembrane protein tyrosine phosphatase and is a receptor for pleiotrophin (PTN). RPTPβ/ζ interacts with ανβ3 on the cell surface and upon binding of PTN leads to c-Src dephosphorylation at Tyr530, β3 Tyr773 phosphorylation, cell surface nucleolin (NCL) localization and stimulation of cell migration. c-Src-mediated β3 Tyr773 phosphorylation is also observed after vascular endothelial growth factor 165 (VEGF165) stimulation of endothelial cells and is essential for VEGF receptor type 2 (VEGFR2) - ανβ3 integrin association and subsequent signaling. In the present work, we studied whether RPTPβ/ζ mediates angiogenic actions of VEGF. Methods: Human umbilical vein endothelial, human glioma U87MG and stably transfected Chinese hamster ovary cells expressing different β3 subunits were used. Protein-protein interactions were studied by a combination of immunoprecipitation/Western blot, immunofluorescence and proximity ligation assays, properly quantified as needed. RPTPβ/ζ expression was down-regulated using small interference RNA technology. Migration assays were performed in 24-well microchemotaxis chambers, using uncoated polycarbonate membranes with 8 μm pores. Results: RPTPβ/ζ mediates VEGF165-induced c-Src-dependent β3 Tyr773 phosphorylation, which is required for VEGFR2-ανβ3 interaction and the downstream activation of phosphatidylinositol 3-kinase (PI3K) and cell surface NCL localization. RPTPβ/ζ directly interacts with VEGF165, and this interaction is not affected by bevacizumab, while it is interrupted by both CS-E and PTN. Down-regulation of RPTPβ/ζ by siRNA or administration of exogenous CS-E abolishes VEGF165-induced endothelial cell migration, while PTN inhibits the migratory effect of VEGF165 to the levels of its own effect. Conclusions: These data identify RPTPβ/ζ as a cell membrane binding partner for VEGF that regulates angiogenic functions of endothelial cells and suggest that it warrants further validation as a potential target for development of additive or alternative anti-VEGF therapies

Can Exercise Affect the Pain Characteristics in Patients with Fibromyalgia? A Randomized Controlled Trial

Exercise is often recommended for fibromyalgia. The aim of this study was to investigate the possible influence and change in the pain characteristics of fibromyalgia patients when breathing exercises were added to their exercise program. A total of 106 patients were included and randomly divided into two groups. &Tau;he first group of patients followed a program of active exercises up to the limits of pain, lasting 30 min with a repetition of two times a week. Patients of the second group followed the same program with the addition of diaphragmatic breaths when they reached the pain limit. The patients completed three questionnaires: the Fibromyalgia Rapid Screening Tool (FiRST), the Brief Pain Inventory (BPI), and the Pain Quality Assessment Scale (PQAS)&mdash;once at the beginning, once again after three weeks of exercise, and again 3 months since the beginning of the program. Independent t-tests for the mean total change scores in pain scales demonstrated that for the second group there was a greater improvement in all pain scales, except for the PQAS Deep Pain subscale (p = 0.38). In conclusion, both groups showed significant improvement in all characteristics of the pain scales; however, the improvement of the second group was significantly higher

Abstracts of the 9th International Organisation of Physical Therapy in Mental Health Conference

This book contains the abstracts of the papers presented at the 9th International Organisation of Physical Therapy in Mental Health Conference, Organized by the International Organisation of Physical Therapy in Mental Health and Greek Scientific Section “Physiotherapy in Mental Health” of PanHellenic Physiotherapists’ Association, held on 4–6 May 2022. It is the biannual conference of the International Organization of Physical Therapy in Mental Health (IOPTMH), and we answered with success the question: Physiotherapy in mental health; what’s next? The highly qualified scientific program, the reputable presenters, and the venue altogether form a powerful motivation for both physiotherapists and other mental health professionals to attend this conference. Conference Title: 9th International Organisation of Physical Therapy in Mental Health ConferenceConference Theme: Physiotherapy in mental health; what’s next?Conference Date: 4–6 May 2022Conference Location: Crowne Plaza Athens - City Centre Hotel, 50, Michalakopoulou Str. GR 11528 AthensConference Organizer: International Organisation of Physical Therapy in Mental Health and Greek Scientific Section “Physiotherapy in Mental Health” of PanHellenic Physiotherapists’ AssociationConference Secretariat - Public Relations: Alpha Public Relations and Integrated Marketing S.A., 55, Pytheou Str. GR 11743 Athen