Naturepulse - Clinical analyses

Clinical analyses of Naturepulse™

Naturepulse™ administers "Software controlled Short voltage impulse Therapy". At the Molecular Biology level this therapy stimulates a local release of two cytokines, Interleukin 1-beta (IL-1β) and TNF-α. The consequence of this is the natural production of endogenous Vascular Endothelial Growth Factor (VEGF) and Nitric Oxide.

Releasing VEGF results in cellular repair, an anti-Inflammatory effect and activation of new micro-circulation. [See: Biological Effects of a Software-controlled Voltage Pulse Generator (PhyBack PBK-2C the original prototype of Naturepulse™) on the Release of Vascular Endothelial Growth Factor (VEGF) In Vivo International Journal of Experimental and Clinical Pathophysiology and Drug Research 2005].

Naturepulse™ has been developed by Globe.

Essential requirements

The essential requirements which require clinical data support are:

Experiments on the therapeutic effects outlined above and
demonstration of the absence of negative side effects.

Available clinical data

Available clinical data is divided in two groups. The first group includes every talk given at national and international conferences, also published by medical companies. That data comes from day to day use of these devices among public institutions.

The second group includes articles published by speciality journals that relate to studies about Naturepulseâ¢. The technology has its origins from studies and research by the inventor, Lorenzo Piccone.

Evaluation of data in terms of suitability to establish security and performance of the device.

Sources

The sources for the first groups of data the following criteria were considered:

Reputation of the researcher or doctor responsible for the study
Reputation of the Medical lnstitution where the study or research happened
Length of time from the first use of the therapy until today, in a given clinic
Number of patients treated with the therapy in a given clinic
Number of patients included in the research,case reports where few patients with particular conditions have been evaluated.

To choose sources for the second group of data we considered the first two criteria.

There are no other devices with the aim to stimulate a local release of VEGF using a non-invasive device. Other known methods are pharmacological (systemic) or invasive.

The relevant standard to which these notes refer is the: "UNI EN ISO 14155: 2012 : Clinical investigation of medical devices for human subjects"

Critical analysis of the data collected - first group

10 5th Conference of Internal Medicine - Palermo 2004 Primitive and secondary treatment of Raynaud with Electro Lorenz : Preliminary Results of an Innovative Approach
Pietrogrande M., Fusi A., Pesenti B. â U.O. di Medicina, Policlinico San Marco di Zingonia, Università di Milano

This research opens up new ways for the treatment of Raynaudâs syndrome.
RHEUMATISM
Official Journal Of The Italian Society Of Rheuma tology - Special Number 3 - 2005 TREATMENT OF NEUROPATHIC PAIN DURING THE cryoglobulinemic SYNDROME : PRELIMINARY RESULTS BY NEURO-ELECTROSTIMULATION
M. Pietrogrande, M. Meroni, A. Pendazzini, B. Pesenti

Results of a study that indicates a new way to treat occasional rheumatic conditions.
PBK (Naturepulse™ THERAPY IN FAILED BACK SURGERY SYNDROME (FBSS): CASE REPORT
C. Angeletti, C. Guetti, L. Merola, A. Paladini, A. Piroli, F. Marinangeli, A. Ciccozzi, I. Marsili, G. Varrassi.

University of L'Aquila, Chair of Anaesthesiology and Reanimation Verona 2006 - Congresso Nazionale AISD (Italian Association for the Study of Pain) Premise: Professor Giustino Varrassi, Chair of Anaesthesiology and Reanimation at l'Università dell'Aquila, was also President of the EFIC (European Federation of IASP Chapters [EFIC] where IASP stands for International Association for the Study of Pain).

This is a particularly interesting "case report". What is known as "Failed Back Surgery Syndrome" is an induced condition (under the heading Failure of Surgery) which consists of a serious worsening of the patient's condition after the surgical procedure.

As another surgery could be even more dangerous, the availability of a non-invasive therapy can increase the quality of life of the patient significantly.
EVALUATION OF A METHODOLOGY FOR THE STUDY OF BIOLOGICAL EFFECTS OF ANTALGIC ELECTROSTIMULATION (PHYBACK, PBK-2C)(Naturepulse™) ON VEGF ACTIVATION
P. Properzi , A. Paladini, A. Piroli, F. Marinangeli, M.G. Cifone, G. Varrassi.

University of L'Aquila, Chair of Anaesthesiology and Reanimation

Verona 2006 - Congresso Nazionale AISD

This is not clinical research, but a molecular biology study. It could be considered a corollary of the research published in the "in vivo" journal.
TREATMENT OF FIBROMYALGIA WITH PBK (Naturepluse™): OUR EXPERIENCE
Angeletti C., Palesse N.*, Guetti C., Noviello F., Ursini L., Piroli A., Marinangeli F., Ciccozzi A., Varrassi G. Chair of Anaesthesiology and Reanimation, University of L'Aquila - *U.O. Hospital of Neurology, San Salvatore Hospital of L'Aquila - V.A.Do. Volunteering for Homecare â L'Aquila. Roma 2008 â Italian Association for the Study of Pain Conference

Fibromyalgia cannot be considered a "rare" pathology, but it should be considered "less frequent". Currently there is no standard way to cure it. All four cases which were followed by Prof. Varrassi's team, indicated a net improvement in the quality of life of the patients and an interesting use of the equipment in therapy.
CASE REPORT: PATIENT WITH NEUROPATHIC PAIN FROM ULCERS>
Authors: L ongo G.; Boccia M.T.Y.; Caraccio V.; Frasca M.G.; Di Bartolomei M.; Tudini C.; Veronesi M.C.; Tufaro P.; Lazzari M.

UNIVERSITY HOSPITAL, TOR VERGATA, U.O.S.D. PAIN MANAGEMENT CENTER (Dir. Prof. A. GATTI)

Roma 2008 - Congre sso Nazionale AISD

This "case report" has been very important because it showed that the therapy can be administered to patients intolerant of analgesics (i.e. Gabapentin).
NATIONAL CONFERENCE A.I.S.D.
Software controlled short voltage impulses generator - PBK-2C (Naturepulse™) : clinical experience

Roma - Angelicum - 8/10 maggio 2008

Authors: Gubernari M.; Boccia M.T.Y.; Santucci M.; Zorbo S.; Rocconi F.; Trenca I.; Manni C.; La Placa E.; Lazzari M.

UNIVERSITY HOSPITAL, TOR VERGATA, U.O.S.D. PAIN MANAGEMENT CENTER (Dir. Prof. A. GATTI)

This is a survey from a very large sample, extracted from all patients that are normally treated with the software controlled short voltage impulses therapy (as of today this number exceeds 10000). 257 patients are considered for the test, where 238 are suffering 11 different osteoarticular conditions and 19 different peripheral vascular diseases. All cases show a significant improvement of the conditions of the patients.
32nd NATIONAL CONFERENCE OF THE ITALIAN ASSOCIATION FOR THE STUDY OF PAIN (A.I.S.D.)
CASE REPORT: PATIENT WITH PAINFUL DIABETIC ULCER TREATED WITH PBK-2C (Naturepulse™)
Silvi Marina (Teramo) - 28/30 May 2009

GATTI A., LONGO G., CECCOBELLI M., SANTUCCI M., ROCCONI F., GALLI C., CARACCIO V., BARBIERO P., LAZZARI M.

Institute of Anaesthesiology, Intensive Therapy and Pain Management Center â University of "Tor Vergata", Rome (Director: Prof. A. F. Sabato)

This is another "case report" which confirms results obtained the year before. However this case is different because diabetes is the cause of the peripheral vascular disease.
32nd NATIONAL CONFERENCE A.I.S.D.
CLINICAL USE OF PBK (Naturepulse™) TREATING OSTEOARTHROSIS: OUR EXPERIENCE
Silvi Marina (Teramo) - 28/30 May 2009

GATTI A., LONGO G., CARUCCI A., D'ERCOLE A., FRASCA M.G., DI PAOLO A., VERONESI M.C., MARTINI L., BARBIERO P., LAZZARI M.

University of Tor Vergata (Rome) - Chair of Anaesthesiology, Intensive Therapy and Pain Management Center (Director Prof. A. F. Sabato)

Another survey, with a sample of 304 patients, which confirms all the significant results of the previous year.
32nd NATIONAL CONFERENCE A.I.S.D.
CLINICAL USE OF PBK-2C (Naturepulse™) TREATING Tension headache: A NEW THERAPEUTIC APPROACH
Silvi Marina (Teramo) - 28/30 May 2009

GATTI A., GUBERNARI M., D'ERCOLE A., SANTUCCI M., BOCCIA M.T.Y., TRENCA I., FRASCA M.G., LAZZARI M.

Institute of Anaesthesiology, Intensive Therapy and Pain Management Center - University of "Tor Vergata", Rome (Director: Prof. A. F. Sabato)

Survey with a sample of 52 patients. Once again the results are positive so we can say that this is a successful therapy against tension headaches, a very frequent condition with a large economic and social impact.
5th Conference of Italian Volleyball Doctors Association
"New therapeutic approach with PBK(Naturepulse™) on a football player experiencing Os Trigonum calcaneal right side"
Ferrara, Sala Convegni CNA

19 September 2009

Gianni Mazzoni - University of Ferrara - Center of Biomedical Sports Studies

Marco Fogli - University of Ferrara - President of the Italian Volleyball Doctors Association

This is a traumatic disease caused by a non-frequent osteo-articular pathology. The authors gathered the applicability of the therapy on sports traumatology in general.
IPA (Indian Podiatric Association)
First International Conference on "High Risk Diabetic Foot".
New Delhi, 22nd November 2009

Clinical and vascular results of PBK (Naturepulse™) Therapy in Neuroischemic Ulcer - A new evidence in Wound Healing.

Prof. Dr. José Luis Lázaro Martínez - Jefe Unidad Pie Diabético - Universidad Complutense de Madrid

Prof. Martinez described personally the effectiveness of the therapy in treating the peripheral vascular disease caused by the diabetes.
Abstracts of the 20th Annual Meeting of the Italian Society of Uro-Oncology (SIUrO)
Rome, Catholic University of the Sacred Heart, 2010

BIOLOGICAL THERAPY FOR CONTINENCE RECOVERY IN PATIENTS PREVIOUSLY SUBMITTED TO RADICAL PROSTATECTOMY: EFFECT OF A NEW SOFTWARE CONTROLLED DEVICE (PHYBACK PBK-2C) (Naturepulse™) FOR PELVIC FLOOR REHABILITATION.

Debora Marchiori, Alessandro Bertaccini, Claudio Ferri, Giuseppe Martorana

Unit of Urology - Policlinico Sant'Orsola-Malpighi

This study describes that this therapy can be used in the field of urinary incontinence.
83rd National Con ference of the Italian Urology Association (SIU) â Milan 2010
Effectiveness of a new rehabilitative therapy (PhyBack PBK-2C) (Naturepulse™) treating chronic bladder pain
Debora Marchiori, Claudio Ferri, Alessandro Bertaccini, Giuseppe Martorana

Unit of Urology - Policlinico Sant'Orsola-Malpighi
34th National Conference AISD - The New Frontiers of Pain Medicine - Riccione, May 2011
Software controlled short voltage impulses generator - PBK-2C (Naturepulse™): clinical experience
Manni C., Malara G., De Meo B., Masucci L., Bellino R., Chidic O., Lazzari M.,

Again a survey that takes a sample of 1502 patients and continues the collection of clinical data as items in 7 and 9 of this document.
38th Nat ional Conference AISD â Bari 2015
Treating inflammatory pain with La So. Co. Short
Divizia M., Lazzari M., Natoli S., Scordo G., Casali M., Dauri M.

Fondazione Policlinico Tor Vergata - HUB Medicina del Dolore - UOC Anaesthesia and Reanimation Director: Prof. Mario Dauri

Sample of 630 patients suffering from vascular or osteoarticular pain. The survey was completed during 2012 and 2014.

Second group

Europa M edicophysica 2004 Dec;40(4):293-301.
A randomised controlled study on the effect of two different treatments (FREMS AND TENS) in myofascial pain syndrome.
Farina S, Casarotto M, Benelle M, Tinazzi M, Fiaschi A, Goldoni M, Smania N.

Section of Rehabilitation Neurology, Department of Neurological and Vision Science, University of Verona, Verona, Italy.

This study reveals FREMS and TENS therapies are equivalent for short-term results treating myofascial pain. TENS is not effective if mid-term results are considered.
Europa Medic ophysica. 2007 Mar;43(1):37-47. Epub 2006 Dec 12.
Frequency rhythmic electrical modulation system (FREMS) on H-reflex amplitudes in healthy subjects.
Barrella M, Toscano R, Goldoni M, Bevilacqua M.

Endocrine and Diabetes Unit, Ospedale L. Sacco, University of Milan, Milan, Italy.

This study shows the therapy can treat patients with motor neuron excitability disease.
Journal of Endocrinological I nvestigation - Springer 2007 Dec;30(11):944-7.
Induction of vascular endothelial growth factor release by transcutaneous frequency modulated neural stimulation in diabetic polyneuropathy.
Bevilacqua M, Dominguez LJ, Barrella M, Barbagallo M.

Endocrinology and Diabetes Unit and LORENZ Research Center, Department of Medicine, Luigi Sacco Hospital (Vialba)-University of Milan, Milan, Italy.

The local release of VEGF occurs with FREMS therapy and does not with other electrotherapies.

It also confirms the success of FREMS therapy in treating diabetic polyneuropathy.
Journal of Diabetes and i ts Complications. 2009 Jan-Feb;23(1):46-8. Epub 2008 Apr 10.
Frequency-modulated electromagnetic neural stimulation enhances cutaneous microvascular flow in patients with diabetic neuropathy.
Conti M, Peretti E, Cazzetta G, Galimberti G, Vermigli C, Pola R, Scionti L, Bosi E.

Department of Medicine, Diabetes and Endocrinology Unit, San Raffaele Scientific Institute and Vita-Salute San Raffaele University, Via Olgettina, 60, 20132 Milan, Italy.

This study demonstrated the enhancement of cutaneous microvascular flow in patients with diabetic neuropathy is visible just after 10 treatments and remains measurable in follow ups after four months.
Medical Engineer ing & Physics Journal - Elsevier. 2010 Mar 5.
Recovery of 0.1Hz microvascular skin blood flow in dysautonomic diabetic (type 2) neuropathy by using Frequency Rhythmic Electrical Modulation System (FREMS).
Bocchi L, Evangelisti A, Barrella M, Scatizzi L, Bevilacqua M.

This study focuses on rationalising the biophysical benefits induced in microvascular flow in diabetic patients after FREMS therapy.

Conclusions

The data collected from these two different investigation flows as mentioned above, their comparison, the long period of time in which research and studies have occurred (11 years), the high number of patients treated (in Italy and abroad, with over 10000 patients treated at Tor Vergata's teaching university) and the wide variety of diseases successfully treated by this therapy, demonstrate that:

Clinical data proves the molecular biology stu dies and research: the local release of VEGF is endogenous, not deriving from platelets or white blood cells.
Therapeutic benefit obtained from the Naturepulse™ therapy (anti-inflammatory action, activation of microvascular flow, analgesic, relaxant action, vasodilatory) are the result of the local release of VEGF. The choice of the condition in which to use this methodology lies with the doctor, even if the condition doesn't appear on the literature discussed above.
Software controlled short voltage impulses,as output by Naturepulse™ (or FREMS) has no contraindications, except for those provided by law, which are valid for any electrotherapy device.
Software controlle d short voltage impulses, as output by Naturepulse™ (or FREMS) does not present incompatibility with other therapeutic procedures. It may be concomitant with pharmacological, physiotherapy or surgical therapies.
No adverse effects have been observed.

Written by Dr Vittorio Malaguti on behalf of
Globe Microsystems Ltd
Casalecchio di Reno, 26 November 2015