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1. General

At the cellular level, the treatment promotes healthy cellular functionality,

in biostimulation and /or in other compatible phenomena with ionic interactions. At the tissue level, the Proionic System® contributes to restore and repair tissue.

The concept of a Proionic effect was first introduced in 20101, 2 in order to identify and characterise the biological responses resulting from an INDIBA® treatment.

1.1 Frequency specific

Phenomena of the Proionic nature have been observed in response to the application of radiofrequency currents of 448 kHz in medical studies 3, 4and experiments l5, 6, 7, 8, 9, 10, 11, 12

2. Effects

2.1 Cell proliferation

Biostimulation:includes described proliferative effects in cultures of ADSC stem cells, derived from activation of intracellular signalling cascades.13

Antiproliferative: the application of Proionic technology over several cell lines of human cancers has revealed cytostatic and cytotoxic effects in them.

These effects would be mediated by cellular phenomena such as blockages of the cell cycle and by phenomena Molecular changes in protein expression involved in the progression of the cycle and in the proliferation mobile.14, 15, 16, 17, 18

Normalization: implies a set of changes in the expression of cell differentiation markers generated by the application of Proionic technology, which would lead to more differentiated phenotypes in certain cell types.19

2.2 Tissue

Antalgic action: the application of Proionic technology in acute and chronic osteoarticular pathology reduces pain, helps eliminate toxic wastes, stimulates the recovery process and improves joint stiffness.

This induces symptomatic relief and accelerates Recovery.20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30

Anti-inflammatory: action as a result of activation Thermo-induced cellular metabolism are enhanced the natural anti-inflammatory mechanisms and the resolution of acute inflammatory conditions. In processes Chronic improves joint mobility, reduces stiffness and improves functional capacity.31, 32, 33 It has been proposed that in this anti-inflammatory action mediation would intervene of the immune system.3, 4

Anti-edematous action: accelerates the absorption of bruises and edemas, by favoring the increase of circulation blood and lymphatic drainage.35, 36

Bone consolidation: there is an activation of the process repair post fracture. 37

Soft tissue healing: accelerates scarring. This effect has been observed in response to postsurgical treatments, in related injuries with burns and in acute musculoskeletal pathology of traumatic origin. It has been linked to an increase of circulation and tissue oxygenation.38, 39, 40

Neo-colagenesis and regenerative activity: induces a tensor effect that, together with a pro-lipolytic activity, would justify the favorable tissue effects obtained in treatments applied in aesthetic medicine.41, 42, 43

3 Applications

Regenerative effects, biostimulators, analgesics and anti-inflammatories of the Proionic System® have allowed its application in various areas of health, in particular:

aesthetic medicine, dermatology, plastic surgery, sports medicine, pain medicine, traumatology, rheumatology, physiotherapy, osteopathy, rehabilitation and integrative medicine.

Recent studies indicate that said applications can be extended to new areas, such as veterinary medicine and the development of therapies for promotion of the general welfare.

4 History

The term Proionic Radio frequency was referred for a time first by Sendrós S. in 2010 in the field of applications of this technology in aesthetic medicine,44 in 2012 Fouquet L. and Delmar H. described their action in skin firming treatments (28). Later Naranjo P. refers to Proionic effects when describing the action promoter of tissue regeneration and the effect of modulation of the inflammatory response, induced by the application of radio-thermic electrothermal currents at 448 kHz 45, 46subsequent to laser treatment fractional. The Proionic concept was proposed with purpose to designate and differentiate a set of biological effects that, although they are not yet fully characterized, have been shown through stimulation electricity with radio frequency currents, and they seem to be specific to the frequency of the applied signal.47, 48

5 References

1 ‘Sendrós S. “INDIBA Deep Beauty: Proionic Body Care System by INDIBA Medical Technology. Foundations and its interest in Medical Aesthetics. Applications. Practical implementation of an Anti-aging Face Protocol. Aesthetics Asia, Singapore, September 17th-19th 2010.

2 ‘Sendrós S. INDIBA Deep Beauty: Proionic Body Care System by INDIBA Medical Technology in Medical Aesthetics. Clinical relevant Guidelines. Applications. Practical implementation of an Abdominal Protocol. Aesthetics Asia Singapore, September 17th – 19th 2010.

3 ‘Naranjo P. Activating natural tissue repair and anti-inflammatory processes with INDIBA® Deep Care. 12th Anti-Aging Medicine World Congress AMWC, 3-5 April 2014, Monte Carlo (Monaco).

4 ‘Naranjo P. Regeneración tisular y modulación de la inflamación post-tratamientos láser con RF de 448 kHz. XXII Jornadas Mediterráneas de Confrontaciones Terapéuticas en Medicina y Cirugía Cosmética, 16-18 Mayo 2014, Sitges (Barcelona), Spain.

5 ‘Naranjo P. Activating natural tissue repair and anti-inflammatory processes with INDIBA® Deep Care. 12th Anti-Aging Medicine World Congress AMWC, 3-5 April 2014, Monte Carlo (Monaco).

6 ‘Naranjo P. Regeneración tisular y modulación de la inflamación post-tratamientos láser con RF de 448 kHz. XXII Jornadas Mediterráneas de Confrontaciones Terapéuticas en Medicina y Cirugía Cosmética, 16-18 Mayo 2014, Sitges (Barcelona), Spain.

7 ‘Hernández-Bule ML, Paíno CL, Trillo MA, Úbeda A. Electric Stimulation at 448 kHz Promotes Proliferation of Human Mesenchymal Cell. Physiol Biochem 2014; 34:1741-1755.

8 ‘Hernández-Bule ML, Trillo MA, Bazan E, Martínez- Pascual MA, Leal J, Úbeda A. Nonthermal levels of electric currents applied in capacitive electric transfer therapy provokes partial cytotoxic effects in human neuroblastoma cultures. Neurocirugia (Astur) 2004;15:366-371; discussion 371.

9 ‘Hernández-Bule ML, Trillo MA, Cid MA, Leal J, Úbeda A. In vitro exposure to 0.57 MHz electric currents exerts cytostatic effects in HepG2 human hepatocarcinomatous cells. Int J Oncol 2007;30:583-592.

10 Hernández-Bule ML, Cid MA, Trillo MA, Leal J, Úbeda A. Cytostatic response of HepG2 to 0.57 MHz electric currents mediated by changes in cell cycle control proteins. Int J Oncol 2010;37:1399-1405.

11 ‘Hernández-Bule ML, Roldán E, Matilla J, Trillo MA, Úbeda A. Radiofrequency currents exert cytotoxic effects in NB69 human neuroblastoma cells but not in peripheral blood mononuclear cells. Int J Oncol 2012; 41:1251-1259.

12 Hernández-Bule ML, Trillo MA, Úbeda A. Molecular mechanisms underlying antiproliferative and differentiating responses of hepatocarcinomatous cells to sub thermal electristimulation. PLoS One 2014; 9:e84636.

13 ‘Hernández-Bule ML, Paíno CL, Trillo MA, Úbeda A. Electric Stimulation at 448 kHz Promotes Proliferation of Human Mesenchymal Cell. Physiol Biochem 2014; 34:1741-1755.

14 ‘Hernández-Bule ML, Trillo MA, Bazan E, Martínez-Pascual MA, Leal J, Úbeda A. Nonthermal levels of electric currents applied in capacitive electric transfer therapy provokes partial cytotoxic effects in human neuroblastoma cultures. Neurocirugia (Astur) 2004;15:366-371; discussion 371.

15 ‘Hernández-Bule ML, Trillo MA, Cid MA, Leal J, Úbeda A. In vitro exposure to 0.57 MHz electric currents exerts cytostatic effects in HepG2 human hepatocarcinomatous cells. Int J Oncol 2007;30:583-592.

16 Hernández-Bule ML, Cid MA, Trillo MA, Leal J, Úbeda A. Cytostatic response of HepG2 to 0.57 MHz electric currents mediated by changes in cell cycle control proteins. Int J Oncol 2010;37:1399-1405.

17 ‘Hernández-Bule ML, Roldán E, Matilla J, Trillo MA, Úbeda A. Radiofrequency currents exert cytotoxic effects in NB69 human neuroblastoma cells but not in peripheral blood mononuclear cells. Int J Oncol 2012; 41:1251-1259.

18 Hernández-Bule ML, Trillo MA, Úbeda A. Molecular mechanisms underlying antiproliferative and differentiating responses of hepatocarcinomatous cells to sub thermal electric stimulation. PLoS One 2014; 9:e84636.

19 Hernández-Bule ML, Trillo MA, Úbeda A. Molecular mechanisms underlying antiproliferative and differentiating responses of hepatocarcinomatous cells to sub thermal electric stimulation. PLoS One 2014; 9:e84636.

20 Bernardi C, Magri B, Barbi E et al. Valutazione dell´effetto della Tecarterapia sul dolore musculo-scheletico: studio osservazonale. 9th Mediterranean Congress of PRM-40 National Congress SIMFER, 21-25 October 2012, Sorrento, Italy.

21 ‘Ronconi G, Specchia A, Maggi Loredana et al. Evaluation of the effects of capacitive and resistive diathermy on knee osteoarthritis. 18th European Congress of Physical & Rehabilitation Medicine 28th May-1st June, 2012, Thessanoliki, Greece.

22 Constantino C, Pogliacomi F, Vaienti E. Cryo-ultrasound therapy and tendonitis in athletes: a comparative evaluation versus laser CO2 and TECAR. Acta Biomed 2005; Apr 76(1): 37-41.

23 Calpe J, García C, Hernández R et al. Nuestra experiencia con un recuperador electrónico en lesiones vasculares de pacientes hemodializados. Rev Soc Esp Dial Trasplant. 1998; 19:19-22.

24 ‘Stella L. Diatermia: trasferimento energetico capacitivoresistivo. XIV International Congress on Sports Rehabilitation and Traumatology. The Accelerated Rehabilitation of the Injured Athlete, 2005.

25 ‘Arnedo F; Andreu A; Til L; Sendrós S, Hellín S. Radiofrecuencia monopolar capacitiva/resistiva 448 kHz en el tratamiento rehabilitador de lesiones de la musculatura isquiotibial derivadas de la práctica deportiva. Congreso FEMEDE. Santander, Spain, 21- 24 noviembre 2012.

26 ‘Sust F; Linde X; Ti L; Figueras, G, Sendrós, S. Radiofrecuencia monopolar capacitiva/resistiva 448 kHz (INDIBA® activ Threapy) en el tratamiento de lesiones músculotendinosas. Congreso FEMEDE. Santander, Spain, 21 – 24 Noviembre 2012.

27 ‘Vall J; Sendrós S; Sust F; Linde X; Til, Ll. Radiofrecuencia monopolar capacitiva / resistiva 448 kHz como Terapia de Rehabilitación en Medicina Deportiva. Análisis retrospective de su aplicación en un Centro de Alto Rendimiento Deportivo (CAR Sant Cugat, Barcelona) durante el period 2009-2011. Jornadas de la AEMB. Bilbao, Spain, 20-23 Junio 2012.

28 Poca V, Foraster L, Ramón R et al. Estudio multicéntrico, aleatorizado y controlado de la eficacia y seguridad del tratamiento con diatermia regenerativa en la tendinitis aquílea, bursitis trocantérea y síndrome temporomandibular. XXXV Congreso Nacional Soc Esp Reumatología, Murcia 20-22.05.2009.

29 Vicent E, Balbastre I, Encinas P et al. Eficacia terapéutica de la hipertermia por trasferencia capacitiva-resistiva en cervicalgias de origen involutivo. 45 Congres SERMEF. Tarragona. 2007.

30 Mi MI Oh, Myeong Heon Jin, Du geon et al. A prospective randomized, placebo controlled study of radiofrequency therapy for the treatment of chronic prostatitis / chronic pelvic pain syndrome. Journal of Urology 2009; 181(4) Suppl. April 26: 122.

31 ‘Ronconi G, Specchia A, Maggi Loredana et al. Evaluation of the effects of capacitive and resistive diathermy on knee osteoarthritis. 18th European Congress of Physical & Rehabilitation Medicine 28th May-1st June, 2012, Thessanoliki, Greece.

32 Constantino C, Pogliacomi F, Vaienti E. Cryoultrasound therapy and tendonitis in athletes: a comparative evaluation versus laser CO2 and TECAR. Acta Biomed 2005; Apr 76(1): 37-41. 33 Calpe J, García C, Hernández R et al. Nuestra experiencia con un recuperador electrónico en lesiones vasculares de pacientes hemodializados. Rev Soc Esp Dial Trasplant. 1998; 19:19-22.

34 Pontiggia P, Pontiggia E, Baronzio GF. Interleukin 2 induction by in vitro hyperthermia. 21st International Clinical Hyperthermia Society. Kallithea (Halkidiki), Greece, October 1998.

35 ‘Hernández-Bule ML, Trillo MA, Cid MA, Leal J, Úbeda A. In vitro exposure to 0.57 MHz electric currents exerts cytostatic effects in HepG2 human hepatocarcinomatous cells. Int J Oncol 2007;30:583-592.

36 Pinto R, Legrand JJ. Manual Práctico de Medicina Estética. 4º Ed. World Congress S.A. Buenos Aires, Argentina 2009: 246-247.

37 Terranova A, Vermiglio G, Arena S et al. Tecarterapia nel trattamento post-chirurgico delle fracture di femore. Eur J Phys Rehabil Med. 2008; 44 (Suppl 1) (3):1-2.

38 ‘Arnedo F; Andreu A; Til L; Sendrós S, Hellín S. Radiofrecuencia monopolar capacitiva/resistiva 448 kHz en el tratamiento rehabilitador de lesiones de la musculatura isquiotibial derivadas de la práctica deportiva. Congreso FEMEDE. Santander, Spain, 21- 24 noviembre 2012.

39 ‘Sust F; Linde X; Ti L; Figueras, G, Sendrós, S. Radiofrecuencia monopolar capacitiva/resistiva 448 kHz (INDIBA® activ Threapy) en el tratamiento de lesiones músculotendinosas. Congreso FEMEDE. Santander, Spain, 21 – 24 Noviembre 2012.

40 ‘Vall J; Sendrós S; Sust F; Linde X; Til, Ll. Radiofrecuencia monopolar capacitiva / resistiva 448 kHz como Terapia de Rehabilitación en Medicina Deportiva. Análisis retrospective de su aplicación en un Centro de Alto Rendimiento Deportivo (CAR Sant Cugat, Barcelona) durante el period 2009-2011. Jornadas de la AEMB. Bilbao, Spain, 20-23 Junio 2012.

41 Yupakorn K, Amornvittayachan O, Montree U. Efficacy of Monopolar Radiofrequency Device on Cellulite Treatment. Srinagarind Med J 2010; 25(4), 258-264.

42 Valentin da Silva RM, arend Barrichello A, Lima M et al. Effect of Capacitive Radiofrequency on the Fibrosis of Patients with Cellullite. Dermatologist Research and Practice 2013, http://dx.doi.org/10.1155/2013/715829.

43 Mancini S. Le terapie integrate in flebologia. In: Trattato di Flebologia e Linfologia. UTET, Torino, Italy, 2001: 769-771.

44 ‘Sendrós S. “INDIBA Deep Beauty: Proionic Body Care System by INDIBA Medical Technology. Foundations and its interest in Medical Aesthetics. Applications. Practical implementation of an Anti-aging Face Protocol. Aesthetics Asia, Singapore, September 17th-19th 2010.

45 ‘Naranjo P. Activating natural tissue repair and anti-inflammatory processes with INDIBA® Deep Care. 12th Anti-Aging Medicine World Congress AMWC, 3-5 April 2014, Monte Carlo (Monaco).

46 ‘Naranjo P. Regeneración tisular y modulación de la inflamación post-tratamientos láser con RF de 448 kHz. XXII Jornadas Mediterráneas de Confrontaciones Terapéuticas en Medicina y Cirugía Cosmética, 16-18 Mayo 2014, Sitges (Barcelona), Spain.

47 Mancini S. Le terapie integrate in flebologia. In: Trattato di Flebologia e Linfologia. UTET, Torino, Italy, 2001: 769-771.

48 Calbet j. Tratado de la Transferencia Eléctrica Capacitiva (TEC). Doyma, Barcelona, Spain. 1992.It is called Proionic System® that therapeutic strategy able to induce a set of bioeffects or responses biological events induced by electric currents radio frequency of thermal or a thermal densities, which are dependent on the frequency of the stimulus signal electric.