Experimental model for the study of the effects of platelet-rich plasma on the early phases of muscle healing

BACKGROUND: There is abundant evidence suggesting that growth factors may play a key role in the healing process, especially in the early stages of inflammation. Despite the reported clinical successes with the use of growth factors there is still a lack of knowledge on the biological mechanism underlying the activity of platelet-rich plasma during the process of muscle healing. The aim of this study was to analyse the early effects of platelet- rich plasma in an easily reproducible animal model. MATERIALS AND METHODS: Wistar male adult rats (n =102) were used in this study. The muscle lesion was created with a scalpel in the flexor sublimis muscles. Platelet-rich plasma was applied immediately after surgery. Treated, untreated and contralateral muscles were analysed by morphological evaluation and western blot assay. RESULTS: Leucocyte infiltration was significantly greater in muscles treated with platelet-rich plasma than in both untreated and contralateral muscles. The latter showed greater leucocyte infiltration when compared to the untreated muscles. Platelet-rich plasma treatment also modified the cellular composition of the leucocyte infiltration leading to increased expression of CD3, CD8, CD19 and CD68 and to decreased CD4 antigen expression in both platelet-rich plasma treated and contralateral muscles. Blood vessel density and blood vessel diameters were not statistically significantly different between the three groups analysed. DISCUSSION: The results of this study showed that treatment with platelet-rich plasma magnified the physiological early inflammatory response following a muscle injury, modifying the pattern of cellular recruitment. Local platelet-rich plasma treatment may exert a direct or, more plausibly, indirect systemic effect on healing processes, at least in the earliest inflammatory phase

Molecular, cellular and physiological characterization of the cancer cachexia-inducing C26 colon carcinoma in mouse

BACKGROUND: The majority of cancer patients experience dramatic weight loss, due to cachexia and consisting of skeletal muscle and fat tissue wasting. Cachexia is a negative prognostic factor, interferes with therapy and worsens the patients' quality of life by affecting muscle function. Mice bearing ectopically-implanted C26 colon carcinoma are widely used as an experimental model of cancer cachexia. As part of the search for novel clinical and basic research applications for this experimental model, we characterized novel cellular and molecular features of C26-bearing mice. METHODS: A fragment of C26 tumor was subcutaneously grafted in isogenic BALB/c mice. The mass growth and proliferation rate of the tumor were analyzed. Histological and cytofluorometric analyses were used to assess cell death, ploidy and differentiation of the tumor cells. The main features of skeletal muscle atrophy, which were highlighted by immunohistochemical and electron microscopy analyses, correlated with biochemical alterations. Muscle force and resistance to fatigue were measured and analyzed as major functional deficits of the cachectic musculature. RESULTS: We found that the C26 tumor, ectopically implanted in mice, is an undifferentiated carcinoma, which should be referred to as such and not as adenocarcinoma, a common misconception. The C26 tumor displays aneuploidy and histological features typical of transformed cells, incorporates BrdU and induces severe weight loss in the host, which is largely caused by muscle wasting. The latter appears to be due to proteasome-mediated protein degradation, which disrupts the sarcomeric structure and muscle fiber-extracellular matrix interactions. A pivotal functional deficit of cachectic muscle consists in increased fatigability, while the reported loss of tetanic force is not statistically significant following normalization for decreased muscle fiber size. CONCLUSIONS: We conclude, on the basis of the definition of cachexia, that ectopically-implanted C26 carcinoma represents a well standardized experimental model for research on cancer cachexia. We wish to point out that scientists using the C26 model to study cancer and those using the same model to study cachexia may be unaware of each other's works because they use different keywords; we present strategies to eliminate this gap and discuss the benefits of such an exchange of knowledge

Sport per disabili: dalla riabilitazione alle Paralimpiadi.

La pratica regolare di esercizio fisico, cioè di attività motoria strutturata determina in soggetti con disabilità locomotoria, ed in particolare in soggetti con mielolesione (tetraplegici e paraplegici), effetti benefici sulla salute. Tali effetti salutari consistono nel miglioramento dell’efficienza cardiovascolare e respiratoria (con un ridotto rischio di incorrere in malattie conseguenti all’aterosclerosi), miglioramento della “fitness” muscolare (forza massima e capacità di protrarre l’esercizio a differenti livelli di contrazione sottomassimale) ed un generale miglioramento della funzionalità motoria con conseguente maggiore autonomia e ridotto stress cardiocircolatorio nelle attività della vita quotidiana. Dagli anni ‘70 in poi, parallelamente al suo uso di tipo fisiatrico, lo sport per i soggetti disabili si è andato sempre più evolvendo, acquistando popolarità e valenza agonistica sempre maggiore tanto da potersi ora considerare, in termini di spettacolo e di significato sociale, alla stessa stregua dello sport per i normodotati. Oggi le Paralimpiadi estive sono considerate per importanza il secondo evento sportivo al mondo (www.paralympic.org). Poichè la pratica sportiva non è però esente da rischi è fondamentale una accurata valutazione dello stato di salute degli atleti che raggiungono l'obbiettivo di gareggiare a livello paralimpico. sulla base di una ventennale esperienza iniziata con le visite paralimpiche di Seoul ‘88, frutto di una collaborazione tra la Scuola di Specializzazione in Medicina dello Sport dell’Università di Roma “Sapienza”, diretta dal Prof. Marco Marchetti, e la allora Federazione Italiana Sport Handicap, è stata messa a punto la visita di idoneità paralimpica

Intensity And Energy Expenditure Of Sports In Elite Paralympic Athletes With Locomotor Disabilities

Symposium Lessons Learned on the Road to Vancouver (Olympic and Paralympic Friday 3:15PM-5:15PM Andrew Pipe,FACSM,University of Ottawa Sports Medicine Issues Committee) Heart Institute Randall L.Wilber,FACSM,United States Olympic Committee Jos de Koning,FACSM,University of Amsterdam Donald McKenzie,University of British Columbia Mark Aubry,Ottawa Sport Medicine Centre Marco Bernardi,University of Rom

Physical Fitness Evaluation of Paralympic Winter Sports Sitting Athletes

Objective: To provide normative values of physical fitness in Paralympic winter sports athletes competing in a sitting posture and to identify the components relevant for successful performance. Design: Cross-sectional study with sports. Setting: The Institute of Sports Medicine and Science of the Italian National Olympic Committee (Rome, Italy). Participants: Fifteen Alpine skiers (3 BP), 16 Nordic skiers (2 BP), 10 curlers (2 BP), and 34 ISH players (7 BP). Independent Variables: Curling, Alpine skiing, Nordic skiing, and ice sledge hockey (ISH). Main Outcome Measures: Physical fitness components. Oxygen uptake peak ((V) over dotO(2peak); L.min(-1) and mL.kg(-1.)min(-1)), mechanical work in a high-intensity exhaustion exercise (MW-HIE; kJ and kJ.kg(-1)), upper-body strength (N and N.kg(-1)), mean explosive power (MEP; W and W.kg(-1)) in a 10-second arm cranking ergometer Wingate test, and fat mass (FM) (% body mass) were primary outcome measures when assessed in the whole sport groups and secondary outcome measures when separating the BP from the others. Results: Based on 1-way analysis of variance and Tukey post hoc test (P < 0.05), (V) over dotO(2peak) and MW-HIE were highest in Nordic skiers (2.9 +/- 0.53 L.min(-1) and 18.3 +/- 3.98 kJ) and similar in ISH players and Alpine skiers (2.5 +/- 0.42 and 2.3 +/- 0.44 L.min(-1) and 17.4 +/- 2.62 and 16.8 +/- 7.41 kJ, respectively). Alpine skiers showed the highest absolute strength values (1210.1 +/- 220.92 N). Curlers had the highest FM (26.2% +/- 7.74%) and the lowest (V) over dotO(2peak) (1.8 +/- 0.35 L.min(-1)), MW-HIE (11.4 +/- 2.40 kJ), and MEP (251.1 +/- 67.16 W). Among the BP, Nordic skiers, ISH players, and Alpine skiers showed (V) over dotO(2peak), MW-HIE, and strength equal to 3.4 +/- 0.43, 2.9 +/- 0.38, and 2.8 +/- 0.18 L.min(-1) and 22.6 +/- 4.04, 19.4 +/- 2.84, and 18.4 +/- 7.86 kJ, respectively. Conclusions: Analyzing physical fitness data of athletes competing in the last 4 winter Paralympic Games, normative values are provided. The specific components that are highly developed in the BP are considered relevant for successful performance

Buckypaper as absorbable adhesive for surgical applications

FONANZIAMENTO pROGETTO DI RICERCA INTERFACOLTA' dIP pARIDE sTEFANINI Chirurgia Generale e Dip di Chimica Anno 2010 prot C26A10HCNR per 5333€ di 35000€TOPICS: Biotecnologia ed innovazioni tecnologiche. Le proposte italiane nella ricerca. BUCKYPAPER AS ABSORBABLE ADHESIVE FOR SURGICAL APPLICATIONS Massimo Chiaretti(1), Andrea Martinelli(2), Giovanna Angela Carru(3), Fabio Procacciante(1), Lucio D’Ilario(2), Emanuela D’Amore(4), Alessandra Maria Chiaretti(5), Fabio Faiola(6) and Paola Consentino(7). (1)Department of General Surgery “Paride Stefanini”, Sapienza University of Rome, Viale del Policlinico 155, Rome, 00161 (Italy) (2)Department of Chemistry, Sapienza University of Rome, P.le Aldo Moro 5, Rome, 00185 (Italy) (3)Policlinico Umberto I Hospital, Sapienza University of Rome, Viale del Policlinico 155, 00161 - Rome (Italy) (4)National Health Institute, Viale Regina Elena 299, 00161 - Rome (Italy) (5)Biologic Sciences Faculty, University of Rome, P.le Aldo Moro 5, Rome, 00185 (Italy) (6)Department of Molecular Medicine, Sapienza University of Rome, Viale Regina Elena 324, Rome, 00161 (Italy) (7)Appialab Srl V. Latina, 286 00179 Rome (+39) 067825111www.appialab.it E-mail: [email protected] Keywords: buckypaper, carbon nanotubes, medical application, abdominal surgery, wet adhesion absorbable adhesive device. Introduction: The adhesion of a surface on a biological tissue represents an important scientific and technological issue which excites the interest of many researchers. One of the main problems related to the abdominal prosthetic surgery is the mesh fixation. On the one hand suture line tension, mesh separation or displacement, improper and blind application of metal tacks and staples in laparoscopy surgery are the main causes of complications, including seroma, postoperative pain and recurrence[6-9]. On the other hand, the use of human fibrin as glue between the prosthesis and the damaged tissue, although it has become a well-established surgical procedure, presents possible risks associated to the transmission of unknown diseases related to the use of human blood-derived materials [9]. Moreover, it was observed that an increased incidence of postoperative seroma is associated to the use of fibrin glue for mesh fixation[10]. Surfaces able to adhere promptly and strongly on wet biological tissue may represent an effective alternative to the conventional prosthesis fixation methods. This study proposes the application of the nature inspired micro- or nano-patterned adhesive surfaces, by exploiting the scaling effect, according to which the adhesion strength can be enhanced through the reduction of interface adhesive contact size. We experimented evidences on the potential applicability on wet biological tissue of the Buckypaper (BP) as an adhesive tape: BP is a self-standing felt composed of entangled multi-walled carbon nanotubes. In vitro bench surgery mechanical peeling and shear adhesion tests and In vivo tests If compared to other commercial tested prosthesis meshes, BP shows a stronger adhesion, only on wet tissues. much better than both self-gripping commercial mesh and fibrin-glue non-gripping meshes and fabrics. Prompted by these results, we implanted BP in rabbits, to assess its effectiveness as adhesive absorbable prosthetic device and its biocompatibility. After 35 days from the operation we observed that no rabbit behavioral alteration occurred; the BP samples preserved their position in the implantation site and mechanical adhesion was enhanced. This is indicative of no toxicity, good integration and slow reabsorption of the synthetic material into the surrounding tissue without eliciting adverse reactions. Materials and Methods. Operated New Zeeland 3000g female rabbits (R1-R4) did not show mortality or morbidity, no significant neurovegetative or behavioral differences in comparison with the no operated control R5. Results and Discussion. Body weight monitoring graph do not showed any significant difference. The Hematoxilin and Eeosin (H&amp;E) stained implant section reported BP surface fragmentation, shows the formation of a capsule of loose fibrous tissue, consisting of fibroblasts and collagen fibers, indicative of a weak inflammation reaction., the necroscopy examination of R2 showed that the implanted PP favors a cicatrisation process, the mesh appearing wrapped in the inflammatory reaction. In R4, the no sutured incision, tighten by the BP strep, was normally closed and healed. On the smooth BP surface facing the abdominal cavity, explanted from R3, a scarcely adherent neo-formed protein fibrous carpet, about 5 mm thick, may be observed in scansion electronic microscope (SEM). Conclusions: by peeling and shear mechanical tests, a strong BP adhesion on wet biological tissue was measured. In view of a possible application as adhesive absorbable tape in surgery, preliminary in vivo experiments were carried out on rabbit model. Necroscopical and histological investigations enlighten that 35 days after the implantation, the BP elicits minimal adverse tissue response, and when exposed to the peritoneal cavity, no adhesion of omentum or intestinal loops was observed. Nanometric carbon nanotube aggregates, deriving from the surface BP fragmentation, were phagocytised by macrophages and observed in Bowman's urinary space. The assessment of the BP debris, possible toxicity or confinement or metabolism and accumulation or excretion mechanism needs further studies. However, we believe that the results here reported can be used to propose the BP as a new wet absorbable adhesive tape to fix prosthetic materials. References 1. L. Liu, W. Ma, Z. Zhang,Small 2011, 7, 1504 2. M. Chiaretti, G. Mazzanti, S. Bosco, S. Bellucci, A. Cucina, F. Le Foche, G. A. Carru, S. Mastrangelo, A. Di Sotto, R. Masciangelo, A. M. Chiaretti, C. Balasubramanian, G. De Bellis, F. Micciulla, N. Porta, G. Deriu, A. Tiberia, J. Phys.: Condens. Matter 2008,20, 474203 3. A. Di Sotto, M. Chiaretti, G. A. Carru, S. Bellucci, G. Mazzanti, Toxicol. Lett. 2009, 184, 192 4. S. Bellucci, M. Chiaretti, A. Cucina, G.A. Carru,A.I. Chiaretti, Nanomedicine 2009, 4, 531 5. a) The mean equivalent radius was evaluated by wicking tests carried out in water, assuming a water contact angle of about 80°; b) G. Callegari, I. Tyomkin, K. G. Kornev, A.V. Neimark, Y-L. Hsieh, J. Colloid Interface Sci.2011, 353, 290 6. B. P. Jacob, N. J. Hogle, E. Durak, T. Kim, D. L. Fowler, Surg. Endosc. 2007, 21, 629 7. J. R. Eriksen, J. I. Bech, D. Linnemann, J. Rosemberg, Hernia 2008, 12, 483 8. W. B. Gaertner, M. E. Bonsack, J. P. Delaney, Hernia 2010, 14, 375 9. S. Olmi, A. Addis, C. Domeneghini, A. Scaini, E. Croce, Hernia. 2007, 11, 211 10. S. Bellucci, M. Chiaretti, P. Onorato,F. Rossella, M. S. Grandi, P. Galinetto, I. Sacco,F. Micciulla, Nanomedicine 2010, 5, 209 11. massimochiaretti.wordpress.co

ABSORBABLE ADHESIVE FOR LAPAROSCOPIC APPLICATIONS

One of the main problems of abdominal prosthetic surgery is the mesh fixation. Surfaces able to adhere promptly and strongly on wet biological tissue may represent an effective alternative to the conventional prosthesis fixation. Our VIDEO proposes the application of the nature inspired micro- or nano-patterned adhesive surfaces. We realized the intervention with 2 trocar in treated group vs 3 trocar in control group on pig model and operating time in the treated was 10’vs 60’in control group.ClinicalTrials.gov Identifier: NCT02137018 https://register.clinicaltrials.gov prot. C26A10HCNR, founding of 35000€ Prof Lucio D'Ilario, Prof. Andrea Martinelli, Dott. Massimo Chiaretti , prot letter 0003306 project n° 304P25, interfaculty Chemistry Dep, General Surgery Paride Stefanini Dep. http://www.uniroma1.it Location National Health Institute (ISS Istituto Superiore di Sanità), Viale Regina Elena 299 Rome, Roma, Italy, 00161 "BP as a New Device for Surgery and Solid Cancer and Hematopoietic System Tumors Treatment. Effects of BP Implantation" (DM159) ClinicalTrials.gov Protocol and Results Registration System (PRS) Receipt Release Date: 12/30/2014 The objective of this project is to obtain results that can direct the search for the ultimate realization of a prosthetic device for use in abdominal surgery. Will be conducted systematic experiments in 30 New Zealand female rabbits (R1-R30), weighting about 3000 g (Harlan Laboratories)