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Effects of Spa therapy on anti-oxidative status, inflammation, immune system Prof. Dr. M. Zeki Karagülle Symposium o n Research i n Spa Medicine Aix - les - Bains - November 17th 2006 Bourget lake          P ractical information Microclimate Ports       E xceptional surroundings

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Effects of spa therapy on anti oxidative status inflammation immune system l.jpg

Effects of Spa therapy on anti-oxidative status, inflammation, immune system

Prof. Dr. M. Zeki Karagülle

Symposium on Research in Spa Medicine

Aix-les-Bains - November 17th 2006


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Bourget lake    inflammation, immune system

      Practical information

Microclimate

Ports

      Exceptional surroundings

      Famous residents   

Department of Medical Ecology & Hydroclimatology

Istanbul Medical Faculty, Istanbul University


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Spa therapy and Balneotherapy inflammation, immune system

  • Do they have biologic effectson Immunesystem and Inflammation

  • and Oxidation ?

  • Which mechanisms and mediators are involved?


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Terminology inflammation, immune system

  • Spa therapy; a complex intervention at a spa resort, (balneotherapy + others)

  • Balneotherapy ; Mineral/thermal water therapy (Bathing + Drinking + Inhalation)


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Inflammation inflammation, immune system

  • the first response of the immune system to infection or irritationcharacterised by the following quintet:

  • redness (rubor),

  • heat (calor),

  • swelling (tumor),

  • pain (dolor)

  • dysfunction of the organs involved (functio laesa)

  • The first four characteristics have been known since ancient times and are attributed to Celsus; functio laesa was added to the definition of inflammation by Rudolf Virchow in 1858.


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Immune System inflammation, immune system

A scanning electron microscope (SEM) image of a T-lymphocyte (right), a platelet (center), and a red blood cell (left).

Image: The National Cancer Institute at Frederick


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Inflammation inflammation, immune system

Chrousos G. N Engl J Med 1995;332:1351-1363


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Cytokine Signaling Pathways Involved in Inflammatory Arthritis

Choy E and Panayi G. N Engl J Med 2001;344:907-916


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Cytokines and Other Mediators of Inflammation That Influence the Hypothalamic-Pituitary-Adrenal Axis

Chrousos G. N Engl J Med 1995;332:1351-1363


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Spa the Hypothalamic-Pituitary-Adrenal Axis-and Balneotherapy Studies on Anti-oxidative status

  • Anti-oxidant status in patients with Rheumatoid Arthritis after Spa Therapy M KARAGÜLLE, MZ KARAGÜLLE , O KARAGÜLLE, A AVCI , İ DURAK35th Congress of ISMH, June 6-10, 2006, Istanbul

  • The Effect of Balneotherapy on Oxidant-Antioxidant Systems in Primary OsteoarthritisHN AKSOY, N ERDOĞAN, Ö AKSOY, GÖ ERATA, AH KAYAR, MZ KARAGÜLLE 35th Congress of ISMH, June 6-10, 2006, Istanbul


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Malondialdehyde (MDA) nmol/mL the Hypothalamic-Pituitary-Adrenal Axis

After 2-week spa therapy;

  • increased in SPA group, decreased in control group

  • No statistically significant change intergroup (p=0.5) and between group (p=0.2) comparisons


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Nonenzymatic Superoxide Radical Scavenger Activity (NSSA) U/mL

After 2-week spa therapy;

  • increased in both groups

  • Statisticaly significant increase in SPA group (p<0,05)


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Antioxidant Defense Potential (AOP) U/mL U/mL

After 2-week spa therapy;

  • increased in both groups İn spa group agreater extend but , not statistically significant


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Discussions U/mL

Increased levels of MDA (although not statistically significant) suggests that;

  • Per-oxidation reactions are accelerated during or after spa therapy

  • spa therapy may cause an extra oxidative stress


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Discussions U/mL

Increased levels of NSSA (statistically significant) and AOP suggests that;

  • antioxidant potential and activity are improved


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The Effect of Balneotherapy on Oxidant-Antioxidant Systems in Primary OsteoarthritisHN AKSOY, N ERDOĞAN, Ö AKSOY, GÖ ERATA, AH KAYAR, MZ KARAGÜLLE 35th Congress of ISMH, June 6-10, 2006, Istanbul

  • Decreasein MDA levels in patients with high MDA levels

  • Increasein MDA levels in patients with low MDA levels

  • Increase in TAA levels in male patients

  • Decrease in TAA levels in females (menopause-estrogens deficiency?)


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The Effect of Balneotherapy on Oxidant-Antioxidant Systems in Primary OsteoarthritisHN AKSOY, N ERDOĞAN, Ö AKSOY, GÖ ERATA, AH KAYAR, MZ KARAGÜLLE 35th Congress of ISMH, June 6-10, 2006, Istanbul

  • Spa therapy decreases oxidant stress ?!

  • Decrease in oxidant stress is more prominent

  • Increase of antioxidant defence is less manifest


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Free radicals and thermal water-controlled pilot study in Primary OsteoarthritisT BENDER,G NAGY,J BARISKA,R VÁGHY,R GOMEZ,I KOVÁCS4.Turkish-Hungarian Balneological Meeting, 25-26 January, Izmir, 2006

  • Patients: Spondylosis lumbalis N:30(10 in each group)

  • They got no NSAID and steroids, no other disease

  • Duration of the bath 30 minutes, at 34°C

  • Blood samples were taken before the first bath, after the first bath and at end of 10 baths


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Free radicals and thermal water-controlled pilot study in Primary OsteoarthritisT BENDER,G NAGY,J BARISKA,R VÁGHY,R GOMEZ,I KOVÁCS4.Turkish-Hungarian Balneological Meeting, 25-26 January, Izmir, 2006

  • There is difference between tap water and mineral water therapy concerning the effects on the free radicals

  • The changes during tap water therapy may be due to the thermal effect


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Effect of sulfur baths on antioxidative defense systems, peroxide concentrations and lipid levels in patients with degenerative osteoarthritis.

Forsch Komplementarmed Klass Naturheilkd. 2002 Aug;9(4):216-20.

Ekmekcioglu C, Strauss-Blasche G, Holzer F, Marktl W.

Effect of 3-week spa therapy, two groups of patients with and without sulfur baths

Sulfur bath therapy could cause a reduction in oxidative stress, alterations of SOD activities


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[Effect of sulfur administration on lipid levels, antioxidant status and peroxide concentration in health resort patients] [Article in German]

Forsch Komplementarmed Klass Naturheilkd. 2000 Apr;7(2):75-8.

Scheidleder B, Holzer F, Marktl W.

Effect of a 3-week spa therapy, two groups of patients with and without drinking sulphurous

In both groups similar alterations of the activities of antioxidative enzymes as well as peroxide concentrations could be detected.


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Spa antioxidant status and peroxide concentration in health resort patients] [Article in German]-and Balneotherapy Studies on Inflammation, Immune System

  • Physiological effects studies in healthy subjects

  • In-vitro studies in cell cultures

  • Experimental (animal) models of arthritis studies

  • Therapeutic affects studies in patients groups; ie in patients with rheumatic or dermatological diseases


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Experimental (animal) models of arthritis studies antioxidant status and peroxide concentration in health resort patients] [Article in German]


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The decrease in paw volume in adjuvant injected paws at the end of

the experiment was the greatest in the sulfur group followed by tap water group.

There was not any significant difference between the two experiment and the control groups.


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The chronic arthritis which developed in the non-injected left hind paws reached maximum severity on the 9th day after CFA injection in tap water and control groups and not before the 19th day in the sulfur group.

Later on, edema in the sulfur group decreased statistically more rapidly (p <0.001) compared to the other two groups.


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M left hind paws reached maximum severity on the 9th day after CFA injection in tap water and control groups and not before the 19th day in the sulfur group.ud-bath applications reduced inflammation at day 20, at theend of the treatment, the paw volume was significantly reduced in comparison to the controls (p<0.01)

Indomethacin therapy caused a more rapid reduction of paw volume, significant both at day 15 and at day 20 (p<0.05)


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S left hind paws reached maximum severity on the 9th day after CFA injection in tap water and control groups and not before the 19th day in the sulfur group.tudies in patient groups

  • Rheumatic diseases

    • Osteoarthritis

    • Ankylosing Spondylitis

    • Fibromyalgia

  • Dermatological diseases

    • Psoriasis

    • Atopic dermatitis


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Is left hind paws reached maximum severity on the 9th day after CFA injection in tap water and control groups and not before the 19th day in the sulfur group. immune systeminfluenced in OA patients by balneotherapy ?


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Is left hind paws reached maximum severity on the 9th day after CFA injection in tap water and control groups and not before the 19th day in the sulfur group. immune systeminfluenced in OA by spa therapy (mud pack + balneotherapy) ?


Is immune system influenced in healthy subjects by spa therapy mud pack balneotherapy l.jpg
Is left hind paws reached maximum severity on the 9th day after CFA injection in tap water and control groups and not before the 19th day in the sulfur group. immune systeminfluenced in healthy subjects by spa therapy (mud pack + balneotherapy) ?


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Answer may be found short- and long-term beneficial effects in female patients with Fibromyalgia ?


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Conclusions short- and long-term beneficial effects in female patients with Fibromyalgia ?

The results of the published clinical, experimental, in-vitro and in-vivo studies suggeststhat;

  • Spa therapy and balneotherapy provide

  • Anti-inflammatory

  • Immunosuppressive

  • Immunomodulatory

  • Anti-oxidative

    effects


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Cytokines short- and long-term beneficial effects in female patients with Fibromyalgia ?influenced by spa-and balneotherapy

  • TNF-α

  • IL-1α

  • IL-1β

  • IL-6

  • IFN-γ

  • IL-2

  • IL-4

  • EGF

  • TGF- β1


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Prostaglandines influenced by spa-and balneotherapy short- and long-term beneficial effects in female patients with Fibromyalgia ?

  • PGE2

  • Leukotriene; LTB4

  • PGF2 α


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Matrix Metalloproteinases short- and long-term beneficial effects in female patients with Fibromyalgia ?influenced by spa-and balneotherapy

  • MMP-1

  • MMP-2

  • MMP-3

  • MMP-8

  • MMP-9


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Cell Populations short- and long-term beneficial effects in female patients with Fibromyalgia ?influenced by balneotherapy

  • Langerhans cells

  • T- and B-cells

  • CD4+, CD4- cells

  • CD8+, CD8- cells


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Others short- and long-term beneficial effects in female patients with Fibromyalgia ?

  • CRP

  • Haptoglobuline

  • Substance P


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Conclusions short- and long-term beneficial effects in female patients with Fibromyalgia ?

  • There is high level (1A and 1B) clinical evidence that spa therapy and balneotherapy are effective interventions in the management of rheumatoid arthritis, osteoarthritis, fibromyalgia and ankylosing spondylitis,

  • The mechanisms involved in this efficacy are probably via cytokines and other inflammatory mediators

  • The anti-oxidative mechanisms may be also involved !


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Perspectives short- and long-term beneficial effects in female patients with Fibromyalgia ?

  • The favorable effects of spa and balneotherapy on the cytokines and other mediators of inflammation may create an interesting future for these interventions in the anti-cytokine / ‘‘biologic’’ therapy era.


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Perspectives short- and long-term beneficial effects in female patients with Fibromyalgia ?

  • The favorable effects of spa and balneotherapy on oxidative stress and anti-oxidative status suggest that they may have an important role to play in the rheumatic diseases, as they lower the oxidative stress and the resultant inflammatory damage.


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Conclusions short- and long-term beneficial effects in female patients with Fibromyalgia ?

  • These effects of balneo- and spa therapy seems to differ among different patient groups, but may be also different among spa resorts, thermal/mineral waters used and type of spa treatments provided


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Questions to be answered short- and long-term beneficial effects in female patients with Fibromyalgia ?

  • What are the values of different mineral waters and the specific chemical constituents of mineral waters in observed effects of balneotherapy on inflammatory and oxidative processes?


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Questions to be answered short- and long-term beneficial effects in female patients with Fibromyalgia ?

  • Do exercise, massage and other therapeutic modalities administered during spa therapy course besides balneotherapy, contribute to the overall favorable effects of spa therapy on inflammation and immune processes?


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Questions to be answered short- and long-term beneficial effects in female patients with Fibromyalgia ?

  • If yes, to what extend?

  • And then, how many spa treatments and/or what treatments when combined with balneotherapy constitute the optimal effect ?


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Spa therapy and Balneotherapy short- and long-term beneficial effects in female patients with Fibromyalgia ?

  • Do they have biologic effects

  • on Immunesystem and Inflammation

  • and Oxidation ?

  • Answer seems to be yes;

  • Which mechanisms and mediators are involved?

  • It is not completely understood yet


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We have a long way to go short- and long-term beneficial effects in female patients with Fibromyalgia ?

  • in search of reaching a comprehensive understanding of the ways and mechanisms

  • how the biomarkers, cytokines, hormones and other mediators of inflammation and immune system and oxidative stress and anti-oxidation status are involved,

  • and the roles they play in the effectiveness of spa and balneotherapy


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International Conference short- and long-term beneficial effects in female patients with Fibromyalgia ?

Immune System

and Balneology


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International Conference short- and long-term beneficial effects in female patients with Fibromyalgia ?

Neuro-Immuno-Cutaneous-Endocrine Network

and Balneology


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Thank you for your attention short- and long-term beneficial effects in female patients with Fibromyalgia ?

Merci de votre attention

Merci de votre attention


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