Difference between revisions 439289924 and 439289946 on enwiki

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'''Zerona''' is a low-level laser device applied for non-invasive body slimming of the waist, hips, and thighs.  It has been shown to disrupt [[adipocyte]], or fat cell, membranes causing the release of stored [[lipids]] and fatty material, in turn, promoting adipocyte collapse.  The device was first introduced to the market in 2008 as an [[off-label use]] device for slimming, but later was granted 510k market clearance by the [[Food and Drug (contracted; show full)n C.-H. |last4=Huang |first4=Ying-Ying |journal=Dose-Response |volume=7 |issue=4 |pmid=20011653}}</ref> The development of Zerona required significant clinical investigation to determine the ideal output parameters to ensure optimal efficacy and safety.  Studies evaluated Zerona’s interaction with individual to several million fat cells in order to determine the precise slimming setting.  Zerona is a [[monochromatic]] semiconductor diode laser that emits 5 independent 635&nbsp;nm divergent beams.
  

The four adjustable arms along with the center non-adjustable laser enables the Zerona to concurrently treat the waist, hips, and thighs for complete slimming of the mid-section.

== History ==

(contracted; show full)

The next logical transition was to evaluate the body’s capacity to remove the liberated fatty material, in turn, positioning this technology as a non-invasive body slimming application.{{
factCitation needed|date=July 2011}}

== Mechanism of action ==

The exact mechanism of action for the Zerona is not fully-understood.  As a low-level laser device the theory of action is defined as bioorganic [[photochemistry]], a discipline that explores the interaction between [[photons]] and biochemical pathways within cells.  Like many other science principles, bioorganic photochemistry is defined by laws, and the first law of [[photochemistry]] states that a photoabsorbing structure must be present to yield a clinical outcome. [[Cytoc(contracted; show full)P/ATP exchange [6-8].  It is suggested that laser irradiation increases the rate at which cytochrome c oxidase transfers electrons from cytochrome c to dioxygen [9-11].  Moreover, it has been proposed that laser irradiation reduces the catalytic center of cytochrome c oxidase, making more electrons available for the reduction of dioxygen [12-14].  In turn, an increase in electron and proton transfer increases the quantity of ATP that is synthesized which can directly affect numerous intracellular proteins.
    
The upregulation of ATP induced by laser therapy is also responsible for the increased production of a natural byproduct known as [[reactive oxygen species]](ROS) [15-17].  This highly reactive oxygen molecule participates in numerous pathways within a cell.  However, as the concentration of ROS elevates a process known as [[lipid peroxidation]] can occur where ROS reacts with lipids found within cell membranes temporarily damaging them [18,19].  It has been hypothesized that the Zerona, as a low-level laser device, modulates cell metabolism resulting in a transient rise of ROS which temporarily degrades the membrane creating transitory pores or openings.  Presently, studies are on-going to fully elucidate the underlying mechanism of action.{{factCitation needed|date=July 2011}}

== Clinical trial ==

In 2008, the clinical trial to investigate the efficacy of Zerona commenced.  The trial enrolled 67 subjects, 35 of which were randomly assigned to receive “active” or “real” treatment with 32 randomly assigned to the “sham” or inactive group.  Both groups were asked to sign an affidavit stating that during the clinical trial they would make no changes to their lifestyle and would not participate in any other program or consume any supplements that would promote slimming.  Furthermore, patients were asked to track their daily activities and caloric intake through the entire duration of the trial.  This daily journal ensured that patients were not making any changes that could impact the outcome.    
Patients received treatment every-other day for two weeks receiving a total of 6 treatments.  Patients’ waist, hips, and thighs were treated concurrently for 40 total minutes each treatment, including 20 minutes of anterior or front treatment and 20 minutes of posterior or back treatment.   Measurements were taken at baseline, weeks one and two, and a two-week post-procedure follow-up measurement.  After two weeks the “active” treatment group averaged a cumulative reduction of 3.54&nbsp;inches compared to the “sham” group which averaged a cumulative reduction of just 0.68&nbsp;inches.  At the two-week post-procedure follow-up, “active” group participants did not exhibit a significant gain in their measurements. If the circumference reduction in the study is re-calculated to a radius measure (i.e. a more just measure of fat layer thickness) the actual fat layers on waist, hips and thighs were reduced on average 2.8% or 0.05 inches (0.13 cm) for the "active" group two weeks after the last treatment.<ref name=pmid20014253/> This should be compared to [[cryolipolysis]] which on average results in a 25.5% reduction of fat layer thickness [32].  No adverse events or side-effects were reported during the clinical trial.<ref name=pmid20014253/>    

The clinical trial for Zerona was published in the peer-reviewed journal Laser’s in Surgery and Medicine in 2009.<ref name=pmid20014253/>

== Future applications ==

The adipocyte or fat cell is described as an endocrine organ cell responsible for the synthesis of bioactive peptides which participate in autocrine, paracrine, and endocrine pathways.  The physical adaptability of the adipocyte is extraordinary, enabling it to expand nearly 1,000 fold in volume and 10 fold in diameter in order to store excessive fuel as triglycerides [20].  During periods of limited food intake fat tissue rapidly transitions to an abundant provider of non-esterfied free fatty acids which upon their release into the circulatory system can undergo beta-oxidation to supply energy.  The storage capacity of adipocytes remains a key component of its function but has been shown to modulate the synthesis of bioactive peptides, specifically adipose-derived hormones.{{factCitation needed|date=July 2011}}

Studies have revealed a correlation between deregulated adipose tissue function and excessive fat mass having deleterious effects on the endocrine and immune systems [21-25].  Excessive body fat results in adipocyte hypertrophy or acquired [[lipodystrophy]].  Significant adipocyte expansion is believed to interrupt the interplay of transcriptional factors and other intracellular components yielding pathological consequences [21-25].

(contracted; show full)

An article published in the American Journal of Cosmetic Surgery in 2010 demonstrated a statistically significant reduction in both serum triglyceride and total cholesterol levels following a standard two-week, six treatment Zerona administration [31].  Presently, clinical studies are on-going to elucidate the potential utility of this application.

== References ==

{{reflist}}

6.)	.Karu TI, et al. Exact action spectra for cellular responses relevant to phototherapy. Photomed Laser Surg 2005;23:355-61.
  

7.)	Terenin AN.  Photochemistry of dyes and other organic compounds. Moscow, Leningrad: Acad. Sci. Publ. (1947).

8.)	 Marcus RA, Sutin N.  Electron transfer in chemistry and biology. Biochem. Biophys. 1985;81:265-322

9.)	Passarella S. et al. Increase of proton electrochemical potential and ATP synthesis in rat liver mitochondria irradiated in vitro by helium-neon laser. FEBS Lett. 1984;175:95-9.

10.)	Konev SV, Belijanovich, LM, Rudenok AN.  Photoreactivations of the cytochrome oxidase complex with cyanide: the reaction of heme a3 photoreduction.  Membr. Cell. Biol. (Moscow) 1998;12:743-754.  

11.)	Greco M, et al. Increase in RNA and protein synthesis by mitochondria irradiated with helium-neon laser. Biochem Biophys Res Commun 1989;163:1428-34.    

12.)	Brunori M, Giuffre A, Sarti P. Cytochrome c oxidase, ligands and electrons. J. Inorg. Biochem. 2005;99:324-336.

13.)	Chen CH, Hung HS, Hsu SH. Low-energy laser irradiation increases endothelial cell proliferation, migration, and eNOS gene expression possibly via PI3K signal pathway. Lasers Surg Med. Jan 2008;40(1):46-54.

14.)	Mester E, Korenyi-Both A, Spiry T, Tisza S. The effect of laser irradiation on the regeneration of muscle fibers (preliminary report). Z Exp Chir. 1975;8(4):258-262.

15.)	Klebanov, G.I, Chichuk, T.V., Osipov, A.N. and Vladimirov, Y.A. The role of lipid peroxidation products in the effect of He-Ne laser on human blood leukocytes. Biofizika 2005;50:862-866.

16.)	Vladimirov, I.uA., Klebanov, G.I., Borisenko, G.G. and Osipov, A.N.  Molecular and cellular mechanisms of the low intensity laser radiation effect. Biofizika 2004;49(2):339-50.  

17.)	Geiger, P.G., Korytowski, W. and Girotti, A.W. Photodynamically generated 3-beta-hydroxy-5 alpha-cholest-6-ene-5-hydroperoxide: toxic reactivity in membranes and susceptibility to enzymatic detoxification. Photochem. Photobiol. 1995;62:580-587.  

18.)	Klebanov, G.I, Chichuk, T.V., Osipov, A.N. and Vladimirov, Y.A. The role of lipid peroxidation products in the effect of He-Ne laser on human blood leukocytes. Biofizika 2005;50:862-866.

19.)	Geiger, P.G., Korytowski, W. and Girotti, A.W. Photodynamically generated 3-beta-hydroxy-5 alpha-cholest-6-ene-5-hydroperoxide: toxic reactivity in membranes and susceptibility to enzymatic detoxification. Photochem. Photobiol. 1995;62:580-587.
  
20.)	Marques BG, et al. Association of fat cell size and paracrine growth factors in development of hyperplastic obesity.  Am J Physiol. 1998;275:1898-1908

21.)	Karastergiou K and Mohamed AV.  The autocrine and paracrine roles of adipokines.  Mol Cell Endocrinol. 2010;318(1-2):69-78

22.)	Ukropec J, et al.  Adipokine protein expression pattern in growth hormone deficiency predisposes to the increased fat cell size and the whole body metabolic derangements. J Clin Endocrinol Metab. 2008;93(6):2255-62.

23.)	Goossens GH. The role of adipose tissue dysfunction in the pathogenesis of obesity related insulin resistance.  Physiology & Behavior. 2008;94(2):206-218

24.)	Mariman EC and Wang P.  Adipocyte extracellular matrix composition dynamics and role in obesity.  Cell Mol Life Sci. 2010;67(8):1277-92.

25.)	Gutierrex DA, et al.  Impact of increased adipose tissue mass on infmammation, insulin resistance, and dyslipidemia.  Curr Diab Rep. 2009;9(1):26-32.

26.)	Ahima RS. Adipose tissue as an endocrine organ.  Obesity. 2006;14(suppl 5):242-249.

27.)	Heilbronn LK and Campbell LV.  Adipose tissue macrophages, low grade inflammation and insulin resistance in human obesity.  Curr Pharm Des. 2008;14(12):1225-30. ⏎
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28.)	Bahceci M, et al.  The correlation between adiposity and adiponectin, tumor necrosis factor alpha, interleukin-6 and high sensitivity C-reactive protein levels.  Is adipocyte size associated with inflammation in adults?  J Endocrinol Invest. 2007;3-(2):210-4.    

29.)	Ahima RS. Metabolic actions of adipocyte hormones: focus on adiponectin.  Obesity. 2006;14(Suppl 1):9-15.

30.)	Gavrilova O, et al.  Surgical implantation of adipose tissue reverses diabetes in lipoatrophic mice.  J Clin Invest. 2000;105:271-78.    

31.)	Jackson et al.  Reductions in cholesterol and triglyceride serum levels following low level laser irradiation: A non-controlled, non-randomized pilot study.  Amer J Cosmet Surg. 2010;27(4):177-184.

32.)    Coleman et al. Clinical Efficacy of Non-Invasive Cryolipolysis and its Effects on Peripheral Nerves. Aest Plast Surg, DOI 10.1007/s00266-008-9286-8

[[Category:Laser medicine]]