physiological regulating medicine in immune and endocrine … · 2014-05-27 · extra -cellular...
TRANSCRIPT
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London Saturday October the 6th, 2012
_______________
Physiological Regulating Medicine in Immune and Endocrine Disorders
Alessandro Perra – Scientific Director of GUNA S.p.a.
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Save your time!
Take your DIPLOMA of Specialist in
Physiological Regulating Medicine
www.prmacademy.org
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Physiological Regulating Medicine PRM
PRM codifies the vision of the organism as a psycho-neuro-endocrine-immune NETWORK
regulated by mechanisms of…
FINE CONTROL (through LOW DOSE of messenger molecules acting on membrane
receptors -up-regulation-)
© Dipartimento Scientifico Guna S.p.a.
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P N E I
CENTRAL NERVOUS SYSTEM &
NEUROVEGETATIVE SYSTEMS
IMMUNE SYSTEM
ENDOCRINE SYSTEM
Homeostatic control systems
© Dipartimento Scientifico Guna S.p.a.
Ader, R., Psychoneuroimmunology, IV edition, vol. 1 e 2, Academic Press, Amsterdam 2007. It is the classical text on the matter, pubblished for the first time in 1981.
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HOMEOSTASIS
DISEASE
DISEASE © Dipartimento Scientifico Guna S.p.a.
P N E I
•T° (inflammation; Immune System)
•pH •O2 •Glycemia
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P
N
E
I
P N E I
PSYCHE
SOMA PSYCHE
P.N.E.I. NETWORK AND MESSENGER MOLECULES
© Dipartimento Scientifico Guna S.p.a.
INTERLEUKINS
HORMONES
NEUROPEPTIDES
HORMONES
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Relationship between hormones and cytokines
• The hormones influence cytokines levels and realize a connection between endocrine system and immune system
– FEMALE SEXUAL HORMONES inhibit the Th2 reaction and stimulate Th1 cytokines
– CORTISOL inhibit the Th1 reaction and in particular IL-2. In turn, different interleukins, among which IL-1, IL-6, TNF-α, IFN stimulate ACTH secretion and therefore also cortisol secretion
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Da: PsicoNeuroEndocrinoImmunologia. Francesco Bottaccioli – RED Edizioni
HPA AXIS
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Collins S M, Bercik P. The Relationship Between Intestinal Microbiota and the Central Nervous System in Normal Gastrointestinal Function and Disease. GASTROENTEROLOGY 2009;136:2003–2014
GBA AXIS
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Messenger Molecules
The Foundation for PRM
COMMUNICATING MOLECULES are messengers, the words used by the 3 homeostatic control systems to speak each other …and to understand each
other.
© Dipartimento Scientifico Guna S.p.a.
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DISEASES CAN BE CONSIDERED AS
EXPRESSIONS, CONSEQUENCES OF
CHANGED CONCENTRATION OF
MESSENGER MOLECULES, DUE TO UP-
OR DOWN-REGULATION OF THE P.N.E.I.
AXIS CELLS
P.N.E.I. NETWORK AND MESSENGER MOLECULES
Dipartimento Scientifico Guna S.p.a.
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HEALTH
PHYSIOLOGICAL CONCENTRATION
DISEASE
DISEASE
HYPO-CONCENTRATION
HYPER-CONCENTRATION
10-6
10-15
© Dipartimento Scientifico Guna S.p.a.
4C – X6
C O P E Cytokines & Cells Online Pathfinder Encyclopedia
Version 26.7 (Spring 2011 Edition)
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Messenger Molecules
Quality and Quantity
Not only the right
MESSAGE but also the right “VOLUME”.
13
Dipartimento Scientifico Guna S.p.a.
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TRANS-MEMBRANE RECEPTORS Up- and Down-Regulation
TNF
Cell-surface receptor
Soluble TNF receptor
Cell activation
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The membrane receptor plays a KEY role.
The quantity of “ligand” (hormone, cytokine or neurotransmitor) and the receptor’s ability to bind these molecules (including the
ligand’s affinity to the receptor) are both critical to the process of communication.
ONLY physiologic concentrations are able to activate or reactivate the membrane receptors and consequently, stimulate the physiologic function
of a target cell. 15
UP- AND DOWN-REGULATION
Dipartimento Scientifico Guna S.p.a.
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The affinity of a receptor for the specific cytokine or the specific hormone is very
high.
The dissociation constant (KD) is about 10-9-10 -12
Mire-Sluis A. R, Thorpe R. (editors). Cytokines. Academic Press, London, San Diego, 1998.
UP AND DOWN REGULATION
Dipartimento Scientifico Guna S.p.a.
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PROBLEM Is it possible to modulate the
action of interleukines and hormones?
IF DISEASES ARE EXPRESSIONS, CONSEQUENCES OF
CHANGED CONCENTRATION OF MESSENGER MOLECULES…
Dipartimento Scientifico Guna S.p.a.
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Antagonistic cytokines or hormones are utilized in order to
brake a biological effect.
The concept of BALANCE and the use of cytokines and hormones
©Dipartimento Scientifico Guna S.p.a.
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Th0
Th2 Th1
IL-12, INF-γ IL-4
INF-γ DOWN-REGULATES
IL-12 UP-REGULATES IL-4 UP-REGULATES
IL-4 DOWN-REGULATES
Th subsets cross-regulate expansion and functions each other.
Cooke , A. Th17 in Inflammatory Conditions. 2006, Rev Diabetic Stud 3: 72-7
- Bettelli E. et al. Th17: the third member of the effector T cell trilogy. Current Opinion in Immunology 2007, 19: 652-657
Dipartimento Scientifico Guna S.p.a.
Inflammatory diseases Allergy
THE CONCEPT OF BALANCE – RECIPROCITY of TH CELLS
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How to use the messenger molecules
THE SCALES OF THE BODY
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Th1 Th2
© Dipartimento Scientifico Guna S.p.a.
THE IMMUNE SYSTEM
Clinic use of low dose cytokines
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22 22
Th-1/Th-2 BALANCE
RHEUMATOID ARTHITIS
ALLERGY
Th-2
Th1 Th17
Th2 Th3
© Dipartimento Scientifico Guna S.p.a.
Th1 UP-REGULATION
Th2 DOWN-REGULATION Th1 DOWN-REGULATION
Th2 UP-REGULATION
Th2
Th1
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Focus on:
Relationship among Th1-Th2-Th3
© Dipartimento Scientifico Guna S.p.a.
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Th0
Th2 Th1
Th3
TGF-β DOWN-REGULATES DOWN-REGULATES
Plasticity and Rigidity of
Relationship among Th1-Th2-Th3
© Dipartimento Scientifico Guna S.p.a.
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Single cytokines
and
SUPPORTIVE
THERAPY FOR
CANCER
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Effects of low dose cytokines (IL-12)
on PBMC of human lung carcinoma
in vitro.
© Dipartimento Scientifico Guna S.p.a. in cooperation with: Osp. Le Molinette
Torino
Accepted on May, 15th 2012 - In press: Journal of Cancer Therapy
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IFN-gamma
Th1 IL-12 4C
CD8+
T citotoxic Lymphocites
T suppressors Lymphocites
Th3 Responsable of immundeficiency during cancer
-
+ 29
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1.7 1.7
0.9
4.5
0.8
0.6
0.4
1.8
0.2
0
0.5
1
1.5
2
2.5
3
3.5
4
4.5
5
basale CH3 CH4 placebo IL12 10ng/ml
CD
4/T
reg
day 5
day 10
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basale CH3 CH4 placebo IL12 10 ng/ml
Series1 46.7 67.4 69.7 69.9 66.1
0
10
20
30
40
50
60
70
80
% C
D4
Day 5
CH3 CH4 placebo IL12 10ng/ml
Series1 49.8 66.1 62.6 34.6
0
10
20
30
40
50
60
70
% C
D4
Day 10
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basale CH3 CH4 placebo IL12 10 ng/ml
Series1 30.7 19 48.4 48.3 4.8
0
10
20
30
40
50
60
%C
D4
/IFN
gam
ma
Day 5
CH3 CH4 placebo IL12 10 ng/ml
Series1 32.8 56 46.2 4.2
0
10
20
30
40
50
60
%C
D4
/IFN
gam
ma
Day 10
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Da: PsicoNeuroEndocrinoImmunologia. Francesco Bottaccioli – RED Edizioni
HPA AXIS
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Effects of low dose cytokines (IFN-gamma) on PBMC of human colon carcinoma in vitro.
© Dipartimento Scientifico Guna S.p.a. in cooperation with: Osp. Le Molinette
Torino –Dipartimento di Fisiopatologia Clinica
Preliminary data
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IFN-gamma
Th1
NK-cells
Anti cancer activity
IFN-gamma 4C
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ACTIVATION OF NK-cells IN CANCER PATIENTS
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•INF-gamma 4CH: 20 drops twice a day for 2-4 months (to stimulate CD8+ cells)
+ IL-12: 20 drops twice a day for 2-4 months (to down-regulate Th3) •MELATONIN 4CH: 20 drops twice a day for 2-4 months (to inhibit GH) •SOMATOSTATINE 4CH: 20 drops twice a day for 2-4 months (to inhibit GH)
•GUNA RERIO: 40 3 times a day for very long time
THERAPEUTIC PROPOSAL FOR CANCER
•GUNA-MATRIX: 20 drops twice a day for 2-4 months
+ GUNA-CELL: 20 drops twice a day for 2-4 months
© Dipartimento Scientifico Guna S.p.a.
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GUNA-RERIO
GUNA-RERIO
ONCOGENS ONCOGENIC SUPPRESSORS
SUPPRESSION INDUCTION
P.M. Biava, A. Carluccio – Attivazione dell’antioncogene p53 su differenti tipi di cellule tumorali in vitro a seguito del trattamento con estratti embrionari purificati in diversi stadi di differenziamento cellulare. La Medicina Biologica 1997/2 supplemento
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INFLAMMATION
DRAINAGE
HOMEOSTASIS
HOMEOSTASIS INFLAMMATION AND
DRAINAGE
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©Dipartimento Scientifico Guna S.p.a. EXOGENOUS OR
ENDOGENOUS STRESSOR
HUMAN BODY
HOMEOSTATIC
ALTERATION ADAPTATION
HEALING
RECOVERY
PATHOLOGIC PROCESS
STRESSOR ACCUMULATION
(MATRIX AND CELL
INTOXICATION )
“HYPER” OR “HYPO”
COMPENSATIVE PRODUCTION
OF HORMONES,
INTERLEUKINS,
NEUROTRANSMITTERS
INFLAMMATION 40
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© Dipartimento Scientifico Guna S.p.a.
GUNA-MATRIX TH
E LI
NK
BET
WEE
N D
RA
INA
GE
AN
D
INFL
AM
MA
TIO
N
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INFLAMMATION mother of all the diseases
© Dipartimento Scientifico Guna S.p.a.
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INFLAMMATORY HOMEOSTASIS
DISEASE
DISEASE © Dipartimento Scientifico Guna S.p.a.
P N E I
Collins S M, Bercik P. The Relationship Between Intestinal Microbiota and the Central Nervous
System in Normal Gastrointestinal Function and Disease. GASTROENTEROLOGY 2009;136:2003–2014
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EXTRA-
CELLULAR
MATRIX
MEMBRANE
RECEPTORS
BLOOD
AND
LYMPH
VESSELS
EX
TR
A-C
ELLU
LA
R M
AT
RIX
TH
E F
IELD
OF B
AT
TLE
OF I
NFLA
MM
AT
ION
© Dipartimento Scientifico Guna S.p.a.
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EXTRA -CELLULAR MATRIX HOMEOSTASIS
•HYDROLYSIS OF MATRIX PROTEINS •PROTEASE ACTIVITY •MATRIX REMODELLING •SOL PHASE •INCREASE OF TEMP° •HISTAMINE ACTIVITY •MYELOID TENDENCY •SYMPATHETICOTONY •ACIDOSIS
•RE-SYNTHESIS OF MATRIX PROTEINS •ANTI-PROTEASE ACTIVITY •REBUILDING OF MATRIX •GEL PHASE •DECREASING OF TEMP° •LYMPHOID TENDENCY •VAGOTONY •ALKALOSIS
© Dipartimento Scientifico Guna S.p.a.
SOL PHASE
GEL PHASE
INFLAMMATION
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’70s
“Inflammation is a stereotyped 6 phases
pathologic process”
1. RELEASE OF INFLAMMATORY MEDIATORS due to nervous
input
2. VESSEL DILATATION
3. INCREASE OF VESSEL PERMEABILITY AND FORMATION
OF EXUDATION
4. LEUCOCITES MIGRATION DUE TO CHEMIOTAXIS
5. LYMPHOCITES MIGRATION
6. ELIMINATION due to leucocytes’ phagocitosys, OF TOXINS AND
CATABOLITES OF INFLAMMATORY REACTION.
© Dipartimento Scientifico Guna S.p.a.
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© Dipartimento Scientifico Guna S.p.a.
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’80s-’90s
“Inflammation is a physio-pathologic
process guided in a psyco-neuro-
endocrine-immune way (PNEI)”
• Inflammation is not an immunological phenomenon only but it is
guided by NEURO-IMMUNE-ENDOCRINE MECHANISMS.
• Takes place the concept that inflammation is an opportune
biological process, which has not to be suppressed but
MODULATED.
• Guna-Flam and Guna Low Dose Cytokines don’t block the
inflammatory process but modulate its evolution CONTROLLING
AND REDUCING symptomatology and resolution time.
• Guna-Flam and Guna Low Dose Cytokines don’t block
physiological pathways of inflammation, preserving the self-defense
capability of the body.
© Dipartimento Scientifico Guna S.p.a.
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P N E I
CENTRAL NERVOUS SYSTEM &
NEUROVEGETATIVE SYSTEMS
IMMUNE SYSTEM
ENDOCRINE SYSTEM
Homeostatic control systems
Ader, R. Psychoneuroimmunology, IV edition, vol. 1 e 2, Academic Press, Amsterdam 2007. It is the classical text on the matter, pubblished for the first time in 1981. © Dipartimento Scientifico Guna S.p.a.
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50
PITUATARY GLAND
GH (Growth hormone)
ACTH (Adrenocorticotrope hormone)
ADRENAL CORTEX Desossicorticosterone
(mineralcorticoid)
Cortisol (glucocorticoid)
INFLAMMATION NATURAL SUPPRESSION
OF INFLAMMATION © Dipartimento Scientifico Guna S.p.a.
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Th2
Th1
…in INFLAMMATION
© Dipartimento Scientifico Guna S.p.a.
•IL-1 •TNF-α •IL-6 •IL-8
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Single cytokines
and
INFLAMMATION
52 © Dipartimento Scientifico Guna S.p.a.
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Interleukin 1 (IL-1) cytokine secreted by macrophages, monocytes, dendritic cells, fibroblasts and endothelial cells.
IL-1 SUPPORTS INFLAMMATORY
PROCESSES
© Dipartimento Scientifico Guna S.p.a.
INTERLEUKINE-1 (α; ß)
53
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54
IL-1 and the cell
© Dipartimento Scientifico Guna S.p.a.
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IL-1 (α; ß) ACTION MECHANISM
IL-1 (α; ß) activates: 1. cyclooxygenase type 2 (COX2) 2. prostaglandin E2 (PGE2) 3. prostaglandin D2 (PGD2) 4. nitric oxide (NO)
© Dipartimento Scientifico Guna S.p.a. 55
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CONVENTIONAL DRUGS TO STOP INTERLEUKINE-1 EFFECTS
© Dipartimento Scientifico Guna S.p.a.
NSAIDs CORTISON ASA
- - - COX2 PGE2 NO
56
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Low dose SKA-actived Antibody Anti Interleukins -1 (α and β) in Inflammation
© Dipartimento Scientifico Guna S.p.a.
Anti IL-1 IL-1
COX2 PGE2 NO
-
BLOCK
Anti Interleukins-1 (α; ß) act as NSAIDs, cortisone and, in part, as salicylates , without the negative side effects caused by these allopathic medicines.
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2000s
“Infiammation is studied by a Molecular
Biology point of view”
1. They don’t only identify the UP-REGULATED
CYTOKINES involved in the inflammatory process
but…
2. They discover the CHRONOBIOLOGY
of inflammatory process and understand and define the
BIO-REGULATORY PROCESSES of inflammation.
© Dipartimento Scientifico Guna S.p.a.
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CHRONOBIOLOGY of inflammation
Physiological trend
© Dipartimento Scientifico Guna S.p.a.
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PROBLEM Is it possible to correct the excess or the deficiency of
cytokines, hormones, neuropeptides in inflammation?
IF INFLAMMATION IS EXPRESSION, CONSEQUENCES OF
CHANGED CONCENTRATION OF MESSENGER MOLECULES…
© Dipartimento Scientifico Guna S.p.a.
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Th2
Th3
Th1
…in INFLAMMATION
© Dipartimento Scientifico Guna S.p.a.
•IL-1 •TNF-α •IL-6 •IL-8
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© D
ipa
rtim
en
to S
cie
nti
fico
Gu
na
S.p
.a.
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63
Inflammation Cytokines
© Dipartimento Scientifico Guna S.p.a.
ANTI-Inflammation Cytokines
•IL-1 •TNF-α •IL-6 •IL-8
•Anti-IL-1 •IL-10 •IL-4 •TGF-β 63
RECOVERING THE BALANCE IN INFLAMMATION
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THERAPEUTIC APPROACH WITH LOW DOSE S.K.A. ANTIBODY ANTI IL-1, IL-10, IL-4 & TGF-β
IN INFLAMMATIONS IN GENERAL AND IN MUSCLE-SKELETAL PAIN MANAGEMENT
• Anti IL-1 4CH Decrease of acute inflammation. • IL-10 4CH Decrease of chronic inflammation. • IL-4 4CH Control of autoimmune diseases trigger. •TGF-β 4CH Resolution phase and restitutio ad integrum.
© Dipartimento Scientifico Guna S.p.a. 64
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• Modulation of the neurogenic phase of inflammation*.
• Sensitization of the beta-endorphin peripheral receptors**.
• RES stimulation and hindrance to the possible septic progression of the inflammatory process.
The 3 pillars… in a drug
GUNA-FLAM
© Dipartimento Scientifico Guna S.p.a.
Aconitum* Belladonna*
Ferrum phosphoricum* Apis*
Bryonia* Pyrogenium* Phytolacca*
Natrium pyruvicum* Acidum citricum*
Cu-gluconate*
Anti IL 1-alfa** TGF 1 beta***
IL 10***
• Modulation of the neurogenic, vasal exudative phases of the inflammatory process*.
• Hindrance to the inflammation start point**.
• Potentiation of the immunologic anti-inflammatory activity having Th2-Th3 polarity***.
Aconitum* Beta-endorphin**
Hepar sulfuris
Pyrogenium
Ferrum phosphoricum
Melatonin 4C
Hypophysis porcine 200X
Pineal Gland 6X
Conjunctive tissue 12X
• Regulation of the extracellular matrix function through the modulation of the hypophysary hormons action and the pineal gland stimulation.
65
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•Belladonna
•Apis
•Ferrum phosph.
•Bryonia
•Anti IL-1
•Belladonna
•Apis
•Ferrum phosph.
•Aconitum
•Beta-endorphin
•Bryonia
•Phytolacca
•Β-endorphin
•Belladonna
•Apis
•Phytolacca
All the
remedies
GUNA-FLAM
© Dipartimento Scientifico Guna S.p.a.
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WHY GUNA MEDICATIONS ARE SO
PHYSIOLOGICAL, BIOLOGICAL AND
EFFECTIVE IN INFLAMMATORY
DISEASES MANAGEMENT?
Guna-Flam and Guna Low Dose
Cytokines re-establish the bio-regulatory
capability of the body,
RESINCRONIZING the chronobiology
of inflammation.
© Dipartimento Scientifico Guna S.p.a.
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CHRONOBIOLOGY of inflammation
Pathological trend and restore of physiology through Guna meds
© Dipartimento Scientifico Guna S.p.a.
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GUNA-FLAM
FIRST 72-96 HOUR (Acute inflammation)
+
GUNA Anti IL-1
Chronic inflammation +
GUNA IL-10
Chronic inflammation in chronic degenerative
diseases +
GUNA IL-10 and GUNA TGF-β
AUTOIMMUNE DISEASES: + GUNA IL-4
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GUNA-FLAM and SINGLE CYTOKINES
DIRECTIONS
•10 drops 3 times a day (or 20 drops twice a day)
•ACUTE SYMPTOMATOLOGY: 10 drops every 30 minutes for 2
hours (Guna-Flam and/or Guna Anti IL-1 4CH)
•Children under 6 years: half of the dosage of adults
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Focus on
INFLAMMATION
IN AUTOIMMUNE
DISEASES
© Dipartimento Scientifico Guna S.p.a.
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Th0
Th1 Th3 Th2 Th17
IL1, INF-γ, IL2, TNF-α, IL6, IL8, IL12
IL 10, TGF-β IL4, IL5, IL6, IL9, IL10, IL13, IL 17
Autoimmunity Trigger
AUTOIMMUNE PATOLOGIES Th subsets cross-regulate the expansion and functions of one another. IL-4 stimulates Th2 differentiation and inhibits differentiation of Th1 cells and
inhibits the development of Th17.
- Bettelli E. et al. Th17: the third member of the effector T cell trilogy. Current Opinion in Immunology 2007, 19: 652-657
The central role of Th17 and IL-23 and IL-17 in autoimmune diseases
© Dipartimento Scientifico Guna S.p.a.
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Th2
Th1
Th17
…in Crohn’s disease
© Dipartimento Scientifico Guna S.p.a.
•TNF-α •IFN-γ •IL-17 •IL-12 •IL-8
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74 74
Inflammation Cytokines
© Dipartimento Scientifico Guna S.p.a.
RECOVERING THE BALANCE IN CROHN’S DISEASE
ANTI-Inflammation Cytokines
•Anti-IL-1 •IL-10 •(IL-4)
•TNF-α •IFN-γ •IL-17 •IL-12 •IL-8
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GUT MUCOSA
DIGESTIVE SYSTEM
HOMEOSTASIS
Why G.I. inflammation? -1
© Dipartimento Scientifico Guna S.p.a.
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Inflammatory Bowel Diseases (IBD)
Ulcerative rettocolitis Crohn’s
Th17 Th1
•TNF-α •IFN-γ •IL-17 •IL-12 •IL-8
IL-5 IL-13
Th2
© Dipartimento Scientifico Guna S.p.a.
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Inflammatory Bowel
Diseases
Crohn’s
Disease
Th1/Th17 Mediated
TNF-α
IFN-γ
IL-17
IL-12
IL-8 Possibly
Infective causes
Ulcerative Colitis
Th2 Mediated IL-5
IL-13
Possibly infective causes
Courtesy from Dr. I Bianchi
IMMUNOLOGICAL DIFFERENTIAL DIAGNOSIS (IBD)
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• Sudden (often)
• Diarrhea with bleeding
• Sometime
• Absent
• Diffuse involvement of the mucosa
• Diffused inflammation and friable colon mucosa
• Distal start with proximal diffusion; it can affect left colon or whole colon
• Gradual
• Diarrhea with few or without bleeding
• Common
• Common
• Involvement of the muscle und serum mucosa
• Focal inflammation with mucosa ulcerations
• Proximal start and distal discontinuous development
Start
Perineal
inflammation
Fistulas formation
Symptomatology
Anatomy
Pathology
Proctoscopic
examination
Localization
Ulcerative colitis Crohn’s disease
Courtesy from Dr. I Bianchi
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Symptomatology: clinical features of Crohn’s Disease
• Manifestations – Diarrhea
– Abdominal pain
– Cachexia, anemia
– Intestinal obstruction
– Fissuration and fistulas : anal/perineal, internal/cutaneous
– Systemic manifestations: joints pain, arthritis, iritis, liver diseases, skin damage
Courtesy from Dr. I Bianchi
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Possible aethiologic causes of Crohn’s Disease
• Infectious agents – Mycobacteria
– Viruses
• Altered sensitivity of the host – Altered cell-mediated immunity
– Altered activity of T-suppressor lymphocytes
– Monocytes-macrophage disfunction
– Neutrophiles disfunction
• Immune-mediated intestinal damage – Antibody reactions: autoantibodies
– Antigen-antibody Immunecomplexes
– Immediate hypersensitivity
– Alterations mediated by lymphocytes
• Psychological factors
• Dietetic-environmental factors Courtesy from Dr. I Bianchi
TNF-α
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Physiopathology of the mucosal damage in Crohn’s Disease
The intestinal antigen
determines the mucosal
production of IL-6 that inhibits T REG
cells
Macrophage activation
IL-12
IL-23
Amplification of the Th1 e Th17
reaction
TNF a IFN g
Conditions of high stress Courtesy from Dr. I Bianchi
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Th2
Th1
Th17
…in Crohn’s disease
© Dipartimento Scientifico Guna S.p.a.
•TNF-α •IFN-γ •IL-17 •IL-12 •IL-8
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84 84
Inflammation Cytokines
© Dipartimento Scientifico Guna S.p.a.
RECOVERING THE BALANCE IN CROHN’S DISEASE
ANTI-Inflammation Cytokines
•Anti-IL-1 •IL-10 •(IL-4)
•TNF-α •IFN-γ •IL-17 •IL-12 •IL-8
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85
85
Effects of low dose cytokines (Anti IL-1 α and β; IL-10) in treatment of inflammatory pathologies: use in an animal model of
CROHN’S DISEASE
© Dipartimento Scientifico Guna S.p.a. in cooperation with:
Submitted to: American Journal of Physiology-Gastrointestinal and Liver Physiology
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Cytokines levels
Untr DSSDSS+Allop
DSS+4HC OM
DSS+4CH non OM
0
50
100
150
200
250
300
350
400
IL-1
2 p
g/m
l
Untr DSSDSS+Allop
DSS+4HC OM
DSS+4CH non OM
0
50
100
150
200
250
300
350
IFN
pg
/ml
Untr DSSDSS+Allop
DSS+4HC OM
DSS+4CH non OM
0
100
200
300
400
500
600
700
800
900
TN
F p
g/m
l
Untr DSSDSS+Allop
DSS+4HC OM
DSS+4CH non OM
0
100
200
300
400
500
600K
C p
g/m
l
IL-12* IFN-γ
TNF-α* IL-8
© D
ipa
rtim
en
to S
cie
nti
fico
Gu
na
S.p
.a.
1 2 3 4 5
1 2 3 4 5
1 2 3 4 5
1 2 3 4 5
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Cytokines levels
Untr DSSDSS+Allop
DSS+4HC OM
DSS+4CH non OM
0
200
400
600
800
1000
1200
1400
1600
1800
2000
IL-1
7 p
g/m
l
Untr DSSDSS+Allop
DSS+4HC OM
DSS+4CH non OM
0
200
400
600
800
1000
1200
1400
1600
1800
2000
2200
IL-1
0 p
g/m
l
IL-17
IL-10
© Dipartimento Scientifico Guna S.p.a.
1 2 3 4 5
1 2 3 4 5
Legenda: 1: valori nel topo sano 2: valori nel topo con Crohn 3: valori nel topo con Crohn dopo 7 giorni di trattamento con Anti IL-1+IL-10 a dosaggi farmacologici 4: valori nel topo con Crohn dopo 7 giorni di trattamento con Anti IL-1+IL-10 a concentrazione 4CH SKA 5: valori nel topo con Crohn dopo 7 giorni di trattamento con Anti IL-1+IL-10 a concentrazione 4CH non-SKA
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DSS (Dextran Sodium Sulphate) Anti Il-1 4CH + IL-10 4CH
60 x
BEFORE TREATMENT AFTER TREATMENT
© Dipartimento Scientifico Guna S.p.a.
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We can say that
are a modern, effective,
no side effects Anti TNF-α
© Dipartimento Scientifico Guna S.p.a.
Guna Anti IL-1 4CH
+
Guna IL-10 4CH
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GUT MUCOSA
DIGESTIVE SYSTEM
HOMEOSTASIS
Why G.I. inflammation? -2
© Dipartimento Scientifico Guna S.p.a.
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Commensal bacteria can influence the expression of genes that controll and regulate the function of
Nervous System.
They are also able to influence the enteroendocrine cells secerning tryptophan
CONSEQUENCES
The microbiota
© Dipartimento Scientifico Guna S.p.a.
Increase of immune-reactive P substance (visceral neurotransmitter) with inflammatory activity
Increase of pseudoaffective answer (miseaure of visceral pain)
IBS
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Influence of GI Physiology on the Microbiota
Collins S M, Bercik P. The Relationship Between Intestinal Microbiota and the Central Nervous
System in Normal Gastrointestinal Function and Disease. GASTROENTEROLOGY 2009;136:2003–2014
Under normal conditions, the GI tract provides a
stable habitat for commensal bacteria that supports its structural and functional integrity also
via a physiological, controlled
inflammation
i.e. immunetolerance
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Collins S M, Bercik P. The Relationship Between Intestinal Microbiota and the Central Nervous System in Normal Gastrointestinal Function and Disease. GASTROENTEROLOGY 2009;136:2003–2014
Influence of GI Physiology on the Microbiota
A change in GI physiology provides an altered habitat that in turn supports a different microbiota. This could be a basis for maintaining a state of G.I. dysfunction after perturbation of the microbiota; it could also explain the development and persistence of dysbiosis in conditions in which there is a primary disturbance of GI physiology.
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• Commensal bacteria instruct the immune and
physiologic systems throughout life and are
responsible for the presence of inflammatory
and immune cells in the healthy gut: so called
“physiologic” or “controlled” inflammation
• The physiologic inflammation refers to the
presence of inflammatory cells in the mucosa and
sub-mucosa of the healthy GI tract and reflects the
presence and immunologic accommodation (rather
than immune tolerance) of the intestinal
microbiota.
MICROBIOTA IN CONTROLLED AND UN-CONTROLLED INFLAMMATION
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Infection and loop of colonization and inflammation (AIEC) CEACAM6:
carcinoembryonic antigen-related cell adhesion molecule 6
CCL20: Chemokine ligand 20
Chassaing B, Darfeuille-Michaud A. The Commensal Microbiota and Enteropathogens in the Pathogenesis of Inflammatory Bowel Diseases. GASTROENTEROLOGY 2011;140:1720–1728
Loureiro I et al. Human colostrum contains IgA antibodies reactive to enteropathogenic Escherichia coli virulence-associated proteins: intimin, BfpA, EspA, and EspB. J. Pediatr. Gastroenterol. Nutr. 1998 Aug;27(2):166-71.
Guna-Interleukin 10
Colostro Noni Specific Ig
for EC- Lactoferrin
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Co
lostro
No
ni
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© Dipartimento Scientifico Guna S.p.a.
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GUT MUCOSA
DIGESTIVE SYSTEM
HOMEOSTASIS
Why G.I. inflammation? -3
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Stabilizing GUT integrity and physiology
The optimal therapy for these disorders would
stabilize both host physiology and the bacterial
composition of the GI tract
Colostro Noni
Guna-Bowel Eubioflor
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GUNA BOWEL
Laxative action
Consitutional rebalance
Hepatic stimulation
• Protection of epithelium*.
• Anti-putrefaction and anti-dysbiosis action **.
•Laxative action to treat episodes of irritation of intestinal mucosa.
• Stimulation of intestinal function in general.
• Stimulation of peristalsis.
• Decrease of rectal atony episodes.
• Reduction of portal stasis*.
•Choleretic and cholagogue action**.
Vitamin D* 2X
Skatolum** 6/10X
Aloe 2X
Rhamnus 2X
Rheum 2X
Alumina 6/8X
Bryonia 6/8X Nux vomica 6/8X
Vit. B1 4X, Vit. B3 2X
Vit. B5 2X Colon, porc. 6/12/30X
Rectum porc. 6/12/30X
Kali carb. 6/8/12X
Natrum carb. 6/8/12X
• Regulation of
constitutional proneness
to drainage insufficiency
of the digestive tract.
Carduus 2X*
Collinsonia 2X*
Chelidonium 2X**
Taraxacum off. 2X**
© Dipartimento Scientifico Guna S.p.a.
101
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ETIOPATHOGENESIS OF INTESTINAL
DYSBIOSIS
ALTERATION OF INTESTINAL MICROFLORA
IMMUNODEFICIENCY
REDUCTION OF INTESTINAL DRAINAGE
INTESTINAL FERMENTATION
AND PUTREFACTION
EUBIOFLOR
© Dipartimento Scientifico Guna S.p.a.
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EUBIOFLOR 1
RECOVERY OF INTESTINAL BALANCE
IMMUNOSTIMULATION
INTESTINAL DRAINAGE
ANTI-FERMENTATION E ANTI-PUTREFACTION ACTION ON THE
INTESTINE
•PINK TRUMPET TREE 4X
•CAT’S CLAW 4X
•OKOUBAKA 6X
•COLIBACILLINUM 6/12/30X
•PROTEUS 6/12/30X
•CANDIDA ALBICANS 6/12/30X
•VACCINIUM MYRTILLUS 4X
•PANCREAS SUIS 12X
•MERCURYAMALGAM 6/12/30D200X
•INDOLUM 6/12/30X
•SCATOLUM 6/12/30X
•AETHUSA CYNAPIUM 6X
•CARBO VEGETABILIS 6X
•COLON PORCINE 6/12/30X
•HEPAR SUIS 12X
•GAL BLADDER PORCINE 6X
•NUX VOMICA 6X
•VERATRUM ALBUM 6X
•ALTHAEA OFFICINALIS 4X
•CARDUUS MARIANUS 4X
•TARAXACUM 4X
© Dipartimento Scientifico Guna S.p.a.
EUBIOFLOR
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•IL10 4CH: 20 drops twice a day for 4-6 months
+ •ANTI IL1: 20 drops twice a day for 4-6 months
or GUNA-FLAM: 20 drops twice a day for 4-6 months •IL4 4CH: 20 drops twice a day for 4-6 months, to down-regulate expression of IL-17
•GUNA-BOWEL: 20 drops twice a day for 4-6 months
CROHN’S DISEASE
•GUNA MOOD: 20 drops twice a day for 4-6 months •COLOSTRO NONI: 2 sachets a day for 1-2 months
•EUBIOFLOR: 20 drops twice a day for 4-6 months
Excess of IL12, IL6, TNF-α; IL18
© Dipartimento Scientifico Guna S.p.a.
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Prof. Ivo BIANCHI 105
• Patients with Rheumatoid arthritis – apart from the therapy – have an hyperexpression of pro-inflammatory cytokines, such as TNF alpha, IL-1, IL-6, GM-CSF, and chemokines such as IL-8
• This is somehow compensated by the production of anti-inflammatory cytokines such as IL10 and TGF beta above cytokine’s inhibitors such as IL-1ra and soluble
TNF-R. • However this regulating mechanism is not sufficient to
neutralize TNF alfa and IL-1 hyperproduction.
• TNF alfa is IL-1 regulating factor and is the main pathogenetic factor of inflammation
Rheumatoid Arthritis
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Cytokines and Symptoms
IL-1 Stimulus
Prostaglandins
TNF Stimulus
Metalloproteinasis
IL-6 Systemic symptoms:
Fever
Myalgias
Weight loss
Prof. Ivo BIANCHI 107
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Rheumatoid Arthritis: Cytokinic
structure
Pathogenetic cytokines for the
Osteolysis
IL-1
IL-7
TNF-α
IL-17
Cytokines that inhibit
Osteolysis
IL-4
IL-10
GM-CFS
IFN-γ
108 Prof. Ivo BIANCHI
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IL -1
MONOCYTES/
MACROPHAGES
FIBROBLASTS
PROLIFERATION CHONDROCYTES OSTEOBLASTS
INFLAMMATION SYNOVIAL PANNUS
FORMATION
CARTILAGE BREAKDOWNS
BONE RESORPTION
© Dipartimento Scientifico Guna S.p.a. 109
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RHEUMATOID ARTHRITIS
IMMUNOLOGICAL HYPERACTIVATION
Pathologic inflammatory status
Inhibitory therapy of hyperexpressed cytokines
with
Anti IL-1 4C
Physiological anti-inflammatory response
Boosting of this stimulus
TGF-β 4C
IL-10
Prof. Ivo BIANCHI 110
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•ANTI IL1: 20 drops twice a day for 2-4 months
+ •IL4 4CH: 20 drops twice a day for 2-4 months
•GUNA-MATRIX: 20 drops twice a day for 2-4 months
AUTOIMMUNE DISEASES -RHEUMATOID ARTHRITIS (Theoretical)
•GUNA-FLAM: 20 drops twice a day for 2-4 months •GUNA POLYARTHRITIS (injectable therapy) : according to the Pain Management protocols
Excess of IL1, IL6, IL2, TNF-α, IL17
© Dipartimento Scientifico Guna S.p.a.
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•IL4 4CH: 20 drops twice a day for 4-6 months
+ •IL10 4CH: 20 drops twice a day for 4-6 months
+ •IL11 4CH: 20 drops twice a day for 4-6 months •GUNA MOOD: 20 drops twice a day for 2-4 months
•GUNA-LIVER: 20 drops twice a day for 2-4 months
+ •GUNA-CELL: 20 drops twice a day for 2-4 months (or ACIDUM FUMARICUM INJEEL FORTE: 1 ampoule per os twice a week for 4-6 months)
PSORIASIS
•TAMANU ARNICA: a thin coat of cream on the affected areas twice a day
Excess of IL1α and β, IL8, IL6, IL12, IL 23, IL2, INF-α, IL17
© Dipartimento Scientifico Guna S.p.a.
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Verum Placebo N=15 MEDIA
PASI SCORE A T=0 7,67
DLQI A T=0 5,87
N=15 MEDIA
PASI SCORE A T=3 6,40
DLQI A T=3 4,33
∆PASI(T3-T0) -1,27
∆%PASI(T3-T0) -12,3%
∆DLQI(T3-T0) -1,53
∆%DLQI(T3-T0) -20,8%
N=15 MEDIA
PASI SCORE A T=6 5,20
DLQI A T=6 4,0
∆PASI(T6-T0) -2,47
∆%PASI(T6-T0) -28,3%
∆DLQI(T6-T0) -1,87
∆%DLQI(T6-T0) -26,2%
Placebo Verum N=14 MEDIA
PASI SCORE A T=0 6,36
DLQI A T=0 8,0
N=14 MEDIA
PASI SCORE A T=3 4,21
DLQI A T=3 3,64
∆PASI(T3-T0) -2,14
∆%PASI(T3-T0) -29,3%
∆DLQI(T3-T0) -4,,36
∆%DLQI(T3-T0) -35,7%
N=14 MEDIA
PASI SCORE A T=6 4,36
DLQI A T=6 4,43
∆PASI(T6-T0) -2,0
∆%PASI(T6-T0) -27,7%
∆DLQI(T6-T0) -3,57
∆%DLQI(T6-T0) -42,9%
TREATMENT OF PSORIASIS VULGARIS WITH LOW DOSE CYTKINES (IL-10+IL-4+IL-11)
Dipartimento Scientifico Guna S.p.a.
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Patient 45
T0 222.000.000
T3 months 29.000.000
T6 months FU 25.000.000
Patient 51
T0 11.000.000
T3 months 8.000.000
T6 months FU 6.000.000
HCV CHRONIC HEPATATIS. PILOT STUDY, CASE CONTROL.
TREATMENT WITH LOW DOSE ACTIVATED CYTOKINES. EFFICACY AND SAFETY ANALYSIS.
VIREMIA: UI/ml Dipartimento Scientifico Guna S.p.a.
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©2003 Dipartimento Scientifico Guna S.r.l.
ATOPY
Th2Th1
EXPOSURE SENSITIZATION
ALLERGIC PUZZLE
115
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©2003 Dipartimento Scientifico Guna S.r.l.
Th2Th1 REBALANCE
DRAINAGE ASPECIFIC AND SPECIFIC
DE-SENSITIZATION
ALLERGIC PUZZLE
THE THERAPEUTIC AETIOLOGIC SOLUTION
116
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IMMUNE SYSTEM DISEASE
SWITCH Th1/Th2 : THE REAL “ORIGINAL SIN” OF ALLERGY
WHY? •GENETIC PREDISPOSITION •ENVIROMENTAL FACTORS(Hygenic Hypothesis,
enviroment, indoor and outdoor exposure, diet, vaccine
adjuvants)
© Dipartimento Scientifico Guna S.p.a.
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Th2
Th1
…IN ALLERGY: SWITCH Th1/Th2
© Dipartimento Scientifico Guna S.p.a.
•IL-4 •IL-5
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ALLERGY
THERAPEUTIC STEPS
DRAINAGE
Th1/Th2 REBALANCE
SPECIFIC AND ASPECIFIC
DESENSITATION
TREATMENT OF
SYMPTOMS
AETIOLOGIC
TREATMENT
SYMPTOMATIC
TREATMENT
+
+
© Dipartimento Scientifico Guna S.p.a.
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Th2
Th1
© Dipartimento Scientifico Guna S.p.a.
•IL-4 •IL-5
ATOPY – SWITCH Th1/Th2– ALLERGIC TERRAINE
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The great innovative element brought by PRM is to be able to act on SWITCH Th1/Th2 through mechanisms of immune regulation operated by natural substances (Vicetoxicum hirundinaria or trace elements – see
Guna Alllergy Prev) or messenger molecules (IL-12 e IFN-γ) in physiological low dose (0,01pg/ml) SKA1 able to cross regulate the
immune balance
THAT’S THE DEEP MEANING OF OUR AETIOLOGIC/PREVENTIVE THERAPY FOR ALLERGIES
1. Gariboldi S. et al. – Low dose oral administration of cytokines for treatment of allergic asthma,
Pulmonary Pharmacology & Therapeutics 22 (2009) 497-510, doi: 10.1016/j.pupt.2009.05.002
© Dipartimento Scientifico Guna S.p.a.
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Th0
Th2 Th1
INF-γ, IL-12 IL-4
INHIBITS
STIMULATES STIMULATES
INHIBITS
IL-12
INF-γ
THE CONCEPT OF BALANCE Developing Th subsets results in cross-regulation. While IL-4 stimulates Th2 differentiation and inhibits diffentiation of Th1 cells, IL-12 and IFN-γ stimulates Th1 differentiation and inhibits the development of Th2 cells.
Cooke , A. Th17 in Inflammatory Conditions. 2006, Rev Diabetic Stud 3: 72-7
- Bettelli E. et al. Th17: The third member of the effector T cell trilogy. Current Opinion in Immunology 2007, 19: 652-657
IL-4
© Dipartimento Scientifico Guna S.p.a.
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Th1
Th2
INF-γ 4CH
IL12 4CH
STIMULATES
HINIBITS © Dipartimento Scientifico Guna S.p.a.
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124
124
Effects of low dose cytokines in treatment of inflammatory pathologies: use in an animal
model of allergic asthma
© Dipartimento Scientifico Guna S.p.a. in cooperation with:
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Reviewer #1: INTRUIGING WORK: Low dose oral administration of IL-12 plus IFN-gamma for treatment in murine model of allergic asthma. solve BHR. Anti-asthmatic activity for 8- 15 days confirmed by histological analysis of lungs and balfluid cell count, it is convincing for this murine model. Serum OVA-specific IgE also inhibited by this low-dose activated cytokines solution, SUGGESTING A NOVEL APPROACH.
Low dose oral administration of cytokines for treatment of allergic asthma Volume 22, Number 6, pp 497-510, December 2009 Silvia Gariboldi, Marco Palazzo, Laura Zanobbio, Giuseppina F Dusio, Valentina Mauro, Umberto Solimene, Diego Cardani, Martina Mantovani, Cristiano Rumio and S.G.M.P. contributed equally to this work
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EXPERIMENTAL PROTOCOL
DAY 1
Injection of 1 mg of egg-albumin + 5 mg Al(OH)3 in PBS (IP)
DAY 7
Injection of 1 mg of egg-albumin + 5 mg Al(OH)3 in PBS (IP)
DAY 13
Aerosol of 1 mg of egg-albumin + 5 mg Al(OH)3 in PBS
from DAY 18 until DAY 38 Blood drawing
TREATMENT WITH IL-12+IFN-γ
LUCKY MOUSE
ALLERGIC MOUSE
DAY 27 Injection of 1 mg of egg-albumin + 5 mg Al(OH)3 in PBS (IP)
DAY 30 5% egg-albumin in PBS 0,5. (Aerosol)
DAY 38 Bronchoalveolar
lavage fluid
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0
10
20
30
40
50
60
[IL-
4]
(pcg
/ml)
0
20
40
60
80
100 [I
L-5
] (p
cg/m
l) 120
140
160
180
UNTR OVA UNTR OVA
BALF – after treatment with egg albumin and Al (OH)3
Asthma © Dipartimento Scientifico Guna S.p.a.
Th2
Th1
Legend •1-Untr=healthy mouse •2-OVA=allergic mouse
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Untr OVA OVA+Allo OVA+4CH OVA+4CHn OVA+30CH
0
10
20
30
40
50
60
70
IL-4
pg
/ml
Untr OVA OVA+Allo OVA+4CH OVA+4CHn OVA+30CH
0
20
40
60
80
100
120
140
160
180
IL-5
pg/
ml
Level of IL-4 and IL-5 in mice sera on day 7th of treatment
© Dipartimento Scientifico Guna S.p.a.
1 2 3 4 5
1 2 3 4 5
Treatment plan of allergic mouse with the 2 anti-allergic interleukines in association
(IL-12+IFN-γ) Legenda •1-Untr=healthy mouse •2-OVA=allergic mouse •3-OVA+ALLO=IL-12+IFN-γ in pharmacological concentration •4-OVA+4CH=IL-12+IFN-γ in physiological concentration (4CH) diluted and dinamized •5-OVA+4CHn=IL-12+IFN-γ in physiological concentration (4CH) only diluted but not dinamized
Levels of IL-4
Levels of IL-5
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Untr OVA OVA+Allo OVA+4CH OVA+4CHn OVA+30CH
0
500
1000
1500
2000
2500
IL-1
2 pg
/ml
Untr OVA OVA+Allo OVA+4CH OVA+4CHn OVA+30CH
0
1000
2000
3000
4000
5000
6000
IFN
gam
ma
pg/m
l
Level of IL-12 and INF-γ in mice sera on day 7th of treatment
© Dipartimento Scientifico Guna S.p.a.
1 2 3 4 5
1 2 3 4 5
Treatment plan of allergic mouse with the 2 anti-allergic interleukines in association
(IL-12+IFN-γ) Legenda •1-Untr=healthy mouse •2-OVA=allergic mouse •3-OVA+ALLO=IL-12+IFN-γ in pharmacological concentration •4-OVA+4CH=IL-12+IFN-γ in physiological concentration (4CH) diluted and dinamized •5-OVA+4CHn=IL-12+IFN-γ in physiological concentration (4CH) only diluted but not dinamized
Levels of IL-12
Level of IFN-γ
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pg fg
Unit of measurement… …the mystery… that is not a mystery
4CH 1 fg/mouse
© Dipartimento Scientifico Guna S.p.a.
we give… …we detect in the blood
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UNTREATED 0
OVA=CONTROL (ALLERGIC MOUSE) 20,188±0,613
OVA+ALLO (PHARMACOLOGICAL TREATMENT) 0
OVA+4 CH (4 CH SKA-ACTIVITED TREATMENT) 0
OVA+4 CH n (4 CH not-SKA-ACTIVITED TREATMENT) 19,567±0,685
OVA+30 CH (30 CH SKA-ACTIVITED TREATMENT) 20,788±0,416
Number of cells expressed in cells/BALF (x104)
© Dipartimento Scientifico Guna S.p.a.
Eosinophil numbers in mouse BALF (bronchoalveolar lavage fluid)
on day 20 of treatment
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132
IL-12 versus association of IL-12+IFN-g
0,00
100,00
200,00
300,00
400,00
500,00
600,00
IL-12 IFN-g
OVA+4CH din
OVA+4CH din associazione
association
Blood levels of IL-12 and IFN-γ
Only IL-12
Association IL-12 + IFN-γ
© Dipartimento Scientifico Guna S.p.a.
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IL-12
0,00
5,00
10,00
15,00
20,00
25,00
30,00
Untr OVA+100ng/die OVA+4CH din
[IL
-12]
(pg
/ml)
0
5
10
15
20
25
30
35
40
45
50
Untr OVA+100ng/die OVA+4CH din
[IF
Ng
am
ma] (p
g/m
l)
IFN-g
Safety of clinical use of SKA treated low doses of interleukines
Preliminary datas
© Dipartimento Scientifico Guna S.p.a.
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•Regulation of Th1 – Th2 balance.
•Increase of basophil and mast cell tolerance toward allergic stimuli
•Specific desensitization to Compositae*, Grass** and Urticaceae*** families.
•Modulation of allergic symptoms: edema, redness, itching.
TREATMENT OF ALLERGIC TERRAIN
NON-SPECIFIC DESENSITIZATION
SPECIFIC DESENSITIZATION
SYMPTOM
CONTROL
•Regulation of allergic diasthesis. •Regulation of allergic
metabolic status.
IL 12 4C
INF g 4C
•Vincetoxicum 6X
•Sulphur 12/30/200X
•Natrum sulphur. 12/30/200X
•Mn-gluconate 4X
Citricum ac. 6X
•Natrum pyruvicum 6X
•Succinicum ac. 6X
•Histaminum 12/30/200X
•Serum anguillae 12/30/200X
Ambrosia artemisiae folia 18X**
Wyethia helenioides 18X**
Phleum pratense 18X*
Arundo mauritanica 18X*
Urtica urens 18X***
Parietaria officinalis 18X***
•Black currant bark 1x
• Viburnum opulus T
• Histaminum 12/30/200X
• Sulphur 12/30/200X
GUNA-ALLERGY PREV © Dipartimento Scientifico Guna S.p.a.
134
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•GUNA-ALLERGY-PREV: 20 drops twice a day for 2-4 months
•GUNA-ALLERGY-TREAT: 20 drops twice a day for 2-4 months. As shock therapy: 10 drops every 30” for 2 hours •GUNA-RHINO NOSE SPRAY: 2 sprays in each nostril 4-5 times a day; Acute phase: 2 sprays in each nostril every 30” for 2-3 hours (allergic rhino-conjunctivitis)
RESPIRATORY ALLERGY THERAPY ACCORDING TO THE PRM TRIANGLE OF THERAPY
•GUNA-MATRIX: 20 drops twice a day for 2-4 months
+ •GUNA-BOWEL: 20 drops twice a day for 2-4 months (especially for allergic asthma)
© Dipartimento Scientifico Guna S.p.a.
135
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ALLERGY
THERAPEUTIC STEPS
DRAINAGE
Th1/Th2 REBALANCE
SPECIFIC AND ASPECIFIC
DESENSITATION
TREATMENT OF
SYMPTOMS
AETIOLOGIC
TREATMENT
SYMPTOMATIC
TREATMENT
+
+
© Dipartimento Scientifico Guna S.p.a.
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•Regulation of Th1 – Th2 balance.
•Increase of basophil and mast cell tolerance toward allergic stimuli
•Specific desensitization to Compositae*, Grass** and Urticaceae*** families.
•Modulation of allergic symptoms: edema, redness, itching.
TREATMENT OF ALLERGIC TERRAIN
NON-SPECIFIC DESENSITIZATION
SPECIFIC DESENSITIZATION
SYMPTOM
CONTROL
•Regulation of allergic diasthesis. •Regulation of allergic
metabolic status.
IL 12 4C
INF g 4C
•Vincetoxicum 6X
•Sulphur 12/30/200X
•Natrum sulphur. 12/30/200X
•Mn-gluconate 4X
Citricum ac. 6X
•Natrum pyruvicum 6X
•Succinicum ac. 6X
•Histaminum 12/30/200X
•Serum anguillae 12/30/200X
Ambrosia artemisiae folia 18X**
Wyethia helenioides 18X**
Phleum pratense 18X*
Arundo mauritanica 18X*
Urtica urens 18X***
Parietaria officinalis 18X***
•Black currant bark 1x
• Viburnum opulus T
• Histaminum 12/30/200X
• Sulphur 12/30/200X
GUNA-ALLERGY PREV © Dipartimento Scientifico Guna S.p.a.
137
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Constitutional core
Symptom core
P.N.E.I. core.
Trace elements core
Organ preparation
core
GUNA ALLERGY TREAT
Apis 200X
Cuprum aceticum 12/30/200X
Allium cepa 12/30/200X
Sabadilla 12/30/200X
•Reduction of rhinorrhea, hyperlacrimation, sneezing. •Bronchospasm
Ammonium carb. 12/30/200X
Arsenicum alb. 12/30/200X
Natrum muriat. 12/30/200X
•Regulation of constitutional proneness to allergy
Adrenalinum 6X
Gl. suprarenalis suis 6/12/ 30X
• Overcoming of “allergic stress”
Bronchus porcine 200X
Mucosa nasalis suis 200X
• Modulation of tissue hyperreactivity
Manganese gluconate 4X
•Regulation of constitutional proneness to allergy according to Oligotherapy
Scilla 12/30/200X
Galphimia glauca 12/30/200X
Luffa op. 12/30/200X
Blatta orient. 12/30/200X
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• Modulation of acute
phlogosis* and
hindrance to necrosis
and proliferation
conditions**
•Drainage and recovery of
skin metabolic function*.
Hindrance to proliferation
episodes (fibroblast
hyperfunction)**
•Activation of the RES
and macrophage
function. Defence
against bacterial
overinfections.
• Stimulation of dermis
function. Immune
endocrine rebalance in
autoimmune skin diseases.
GUNA-DERMO
ANTIINFLAMMATORY ACTION
DRAINING AND FUNCTION
STIMULATING ACTION
ANTISEPTIC ACTION
P.N.E.I. REBALANCE
© Dipartimento Scientifico Guna S.p.a.
Belladonna 6C*
Plantago 4C*
Echinacea 6C*
Arsenicum album 6C**
Sulphur 6C
Dulcamara 6C*
Graphites 6C**
Echinacea 6C
Plantago 4C
Melatonin 4C
IL1-beta 7C
IL2 4C
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• Reduction of the muco-respiratory phlogosis* and in particular of the aedema**.
• Reduction of the phlogosis according to the oligotherapy***
• Stimulation on the Th2/Th3 polarity having anti-inflammatory action****
• Control of the vasal congestion and or hypersecretion phenomena (serous and sero-mucous rhinitis)
• Control of the allergic symptomatology*
• Modulation of the Th2 activity by means of theTh1 with reduction of the IL 4 and IL5 activity**
• Hypertonic saline solution causing an immediate local reduction of the nasal congestion due to the osmotic effect of the extracellular substance
GUNA-RHINO
(Nose spray)
ANTI-INFLAMMATORY ACTION
VASOMOTORIC
SYMPTOMATOLOGY
ALLERGIC
SYMPTOMATOLOGY
MEDIUM
Argentum nitricum*
Rosa canina*
Sambucus*
Plantago*
Apis**
Histaminum**
Cu-gluconate***
IL 10****
Melilotus
Cistus
Euphorbium
Apis
Aralia racemosa
Ribes n.*
Plantago* Euphorbium*
Allium cepa* Histaminum*
IL 12**
ING-gamma**
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•IL12 4CH: 20 drops twice a day for 2-4 months
+ •INF-γ 4CH: 20 drops twice a day for 2-4 months
•GUNA-MATRIX: 20 drops twice a day for 2-4months
+ •GUNA-LIVER: 20 drops twice a day for 2-4 months
ATOPIC DERMATITIS
•GUNA-DERMO: 20 drops twice a day for 2-4 months
+ •EUBIOFLOR: 20 drops twice a day for 2-4 months
© Dipartimento Scientifico Guna S.p.a.
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• Modulation of acute
phlogosis* and
hindrance to necrosis
and proliferation
conditions**
•Drainage and recovery of
skin metabolic function*.
Hindrance to proliferation
episodes (fibroblast
hyperfunction)**
•Activation of the RES
and macrophage
function. Defence
against bacterial
overinfections.
• Stimulation of dermis
function. Immune
endocrine rebalance in
autoimmune skin diseases.
GUNA-DERMO
ANTIINFLAMMATORY ACTION
DRAINING AND FUNCTION
STIMULATING ACTION
ANTISEPTIC ACTION
P.N.E.I. REBALANCE
© Dipartimento Scientifico Guna S.p.a.
Belladonna 6C*
Plantago 4C*
Echinacea 6C*
Arsenicum album 6C**
Sulphur 6C
Dulcamara 6C*
Graphites 6C**
Echinacea 6C
Plantago 4C
Melatonin 4C
IL1-beta 7C
IL2 4C
142
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P.R.M. in RESPIRATORY DISEASES
© Dipartimento Scientifico Guna S.p.a.
COLD AND FLU
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•CITOMIX: 10 granules a week for 6-8 weeks. Repeat the cycle after 45 days
•GUNA-FLU: 1 dose a week for 6-8 weeks. Repeat the cycle after 45 days
INFLUENZA
•GUNA-RHINO NOSE SPRAY: 2 sprays in each nostril twice a day for 2 months •COLOSTRO NONI: 1 sachet a day for 1-2 months
© Dipartimento Scientifico Guna S.p.a.
144
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Prevention and treatment of flu
and cold syndromes
© Dipartimento Scientifico Guna S.p.a.
IMMUNESTIMULATION CORE
SYMPTOMATIC CORE
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NK Cells Tc Lymphocites
© Dipartimento Scientifico Guna S.p.a.
IMMUNESTIMULATION CORE
Subnucleus of Specific Immunity
Gamma-interferon
Subnucleus of Aspecific Immunity
SINERGISM
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Anas barbariae 200K
Influenzinum 9C
Vincetoxicum 5C
ECHINACEA 3C
CUPRUM 3C
BELLADONNA 5C
ACONITUM 5C
SYMPTOMATIC REMEDIES CORE
Remedy for the initial phases of the acute fever reaction,
with quick, violent and sudden onset.
Acute local inflammations, in the initial phase. Evolution of Aconitum symptomatology.
Anti-inflammatory and antiseptic
action.
Influential myalgia. Antipyretic activity due to
heat dispersion (convection).
© Dipartimento Scientifico Guna S.p.a.
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© Dipartimento Scientifico Guna S.p.a.
GUNA-COMPLEX 1
GUNA-COMPLEX 1
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P.R.M. in OTOLARYNGOLOGY
•Viral Rhinitis •Allergic Rhinitis •Nasal Polyps •Chronic Sinusitis •Bacterial Tonsillitis •Infectious Mononucleosis •Recurrent Tonsillitis •Tonsillar Hypertrophy •Adenoids Hypertrophy •Otitis media
© Dipartimento Scientifico Guna S.p.a.
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ENT PATHOLOGIES
Inflammation
Acute GUNA-FLAM
Recurrent GUNA-SINUS
Nose Spray
Hypertrophy
Sub acute GUNA-LYMPHO
Chronic GUNA-MATRIX
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•GUNA-FLAM 20 drops twice a day
•CITOMIX 5-10 pellets twice a day
•GUNA-LYMPHO 20 drops twice a day for 2
months at least
•IL-8 4C 10-20 drops twice
a day
BACTERIAL TONSILLITIS
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•GUNA-LYMPHO 10-20 drops twice a day
over an extended period of time (6-7 months)
RECURRENT TONSILLITIS
•CITOMIX 5-10 pellets twice a day
over an extended period of time (6-7 months)
•GUNA-FLAM 10-20 drops twice a day
over an extended period of time (6-7 months)
•ANTI IL-1 4C 10-20 drops 2-3 times a day for 2 months at least
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•Lymphagogue action and stabilization of the vasal walls
tone with consequent reduction of the extudate and
the lymphoedema.
•Hindrance to the proliferative proneness of the
lymphoepitelial tissues •Humoral immunity
stimulation and inhibitory modulation of the
excessive cell mediated compensatory response
•Reduction of the local phlogosis on the
lymphoepithelial tissues.
• Reduction of the lymphatic spasm on inflammatory basis
with following restoration of the lymphatic circulation.
GUNA-LYMPHO
REACTIVATION OF THE
LYMPHATIC
CIRCULATION
HYPERTROPHY AND HYPERPLASY
OF THE LYMPHATIC ORGANS
STRENGHTENING OF THE
IMMUNE DEFENCE
ANTI-INFLAMMATORY
ACTIVITY ON THE
LYMPHOEPITELIAL TISSUES
© Dipartimento Scientifico Guna S.p.a.
Hydrastis 1X Juglans 3X
Graphites 6/12/30/200X
Magnesium phosphoricum 6/12/30/200X
Juglans regia 3X
Calendula 1X Phytolacca 3X
Apis 8X Magnesia phosph.
Myosotis 3X Equisetum 3X Hydrocotile 1X Taraxacum 1X Sarsaparilla 3X
Lymphatic vessel 6X Capillary tisssue 6X
L-Thyroxin 6/12X Vein porcine 6X
D-L Malic Ac./Fumaricum Ac./Pyruvicum Ac. Trychinoil/Natrium oxalac.
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•Th2 Response
LYMPHATIC ENLARGEMENT
•Th1 Response
RECURRENT INFECTIONS
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TONSILLAR HYPERTROPHY
•GUNA-MATRIX 10-20 drops twice a day
over an extended period of time (6-7 months)
•CITOMIX 5-10 pellets twice a day
over an extended period of time (6-7 months)
•GUNA-LYMPHO 10-20 drops twice a day
over an extended period of time (6-7 months)
•IFN-γ 4C 10-20 drops 2-3 times a day for 2 months at least
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ADENOIDS HYPERTROPHY
•GUNA-SINUS Nose Spray
2 spray in each nostril 2-3 times a day for 2 months at
least
• IFN-γ 4C 10-20 drops 2-3 times a day for 2 months at least
•GUNA-MATRIX 10-20 drops twice a day
over an extended period of time (4-5 months)
•CITOMIX 5-10 pellets twice a day in acute phase (10-15 days)
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Matrix drainage Action against toxin
impregnation
Lymphatic drainage
•Stimulation of the energetic
mitochondrial activity.*
•Matrix acidification (promoting
the connective reactivity).**
•Ac. D-L malicum 6X*
•Natrium oxal. 6X*
•Natrium pyruv. 6X*
•NADID 6X*
•Trychinoil 6X*
•Vit. C 2X*
•Ac. L(+) lacticum3X**
•Deactivation (through
inflammation) and neutralization
of the impregnation toxins*.
•Synergic action with Fucus of the
thyroid hormons activating the
sympatheticotonic nervous
system**.
•Pyrogenium 12X*
•Fucus 3X*
•Tyrosine 2X**
•Phenilalanine 2X**
•Histidine 2X**
•Inactive toxins canalization towards the lymphatic circle for the drainage
•Lymphatic vessel 6X
•Matrix hydrolysis*
•Action against the constitutional proneness to a matrix impregnation and to the development of a Dysmetabolic Mesenchymopathy (Sycosis).**
•Matrix solubilization.***
•Hyaluronidase 6X*
•Thuja 6/8/12/30/200X**
•Natrium sulfuricum 6/8/12/30/200X **
•Prolactine 6X***
•DHEA 6X***
•Increase of the Fundamental Substance cynetics (protein hydrolysis, hyper-ionicity, histaminic activity, > temperature) and of the matrix turnover.*
•Sympatheticotonic stimulation.**
•Vagotonic slowdown.***
•IL 6 4C*
•DHEA 6X*
•Pyrogenium 12X*
•Conjunctive Tissue 6X*
•Tyrosine 2X**
•Phenilalanine 2X**
•Histidine 2X**
•Prolactine 6X***
GUNA-MATRIX
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•CITOMIX: 10 granules a week for 6-8 weeks. Repeat the cycle after 45 days
•GUNA-FLU: 1 dose a week for 6-8 weeks. Repeat the cycle after 45 days
IRR
•GUNA-BOWEL: 20 drops twice a day for 2-4 months •GUNA-LYMPHO: 20 drops twice a day for 2-4 months •COLOSTRO NONI: 1 sachet a day for 1-2 months
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•GUNA-RHINO Nose Spray
2 spray in each nostril 2-3 times a day
•GUNA-FLU 1 dose every 8 hours for 2-
3 days
•GUNA-LYMPHO 20 drops twice a day
•IL-10 4C 10-20 drops 2-3
times a day
VIRAL RHINITIS
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• Reduction of the muco-respiratory phlogosis* and in particular of the aedema**.
• Reduction of the phlogosis according to the oligotherapy***
• Stimulation on the Th2/Th3 polarity having anti-inflammatory action****
• Control of the vasal congestion and or hypersecretion phenomena (serous and sero-mucous rhinitis)
• Control of the allergic symptomatology*
• Modulation of the Th2 activity by means of Th1 with reduction of the IL 4 and IL5 activity**
• Hypertonic saline solution causing an immediate local reduction of the nasal congestion due to the osmotic effect of the extracellular substance
GUNA-RHINO
(Nose spray)
ANTI-INFLAMMATORY ACTION
VASOMOTOR
SYMPTOMATOLOGY
ALLERGIC
SYMPTOMATOLOGY
MEDIUM
Argentum nitricum 10X*
Rosa canina 1X*
Sambucus 2X*
Plantago 2X*
Apis 6/12/30/200X**
Histaminum30/200X**
Cu-gluconate 4X***
IL 10 4C****
Melilotus 3X
Cistus 4X
Euphorbium 4X
Apis 6/12/30/200X
Aralia racemosa 1X
Ribes n. MG*
Plantago* Euphorbium*
Allium cepa 6/8/12X* Histaminum*
IL 12 4C**
INF-gamma 4C**
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SINUSITIS • Two types of inflammation occur in sinusitis, contributing variably to the
clinical expression of disease.
CHRONIC SINUSITIS
Allergic component
IL-5
Infectious component
IL-8
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CHRONIC SINUSITIS
•GUNA-FLAM 20 drops twice a day for 2
months at least
•GUNA-LYMPHO 20 drops twice a day for 2
months at least
•GUNA-SINUS Nose Spray
2 sprays in each nostril 2-3 times a day for 2 months at
least
• IL-2 4C 10-20 drops 2-3 times a day for 2 months at least
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Secretions fluidification
Immune stimulation
Secretions drainage
•Control of the phlogosis signs and symptoms of the respiratory
mucosa*
• Reduction of the sinuses inflammation (in particular frontal
sinuses) according to the acupuncture laws
•Argentum nitr. 10X*
•Plantago 2X*
•Pulmonaria 2X*
•Black currant bark MG*
•Allium cepa 6/8/12X*
•Echinacea 3X*
•Pulsatilla 6/8/12X*
Urinary bladder. 10/30/200X**
•Mn-Cu 3X*
•Vit. C 2X*
•Hypertonic saline solution causing an immediate local reduction of the nasal congestion due to the osmotic effect of the extra-cellular substance
•Vicariating drainage towards the nose cave and the pharinx due to centrifugation of the fluidificated secretions
•Mucosa nasalis 6/12/30x
•Pulsatilla 6/8/12x
•Silicea 6/8/112x
•Antibacterial protection due to the RES stimulation*
•Hindrance to the infective progression of sinusitis**
•Echinacea 3x*
•Thymus gland 6/12/30x*
•Hepar sulfuris 6/8/12x*
•Lachesis 12/30/200x**
•Secretolytic and mucoregulating action.
•Secretions fluidification, in particular viscous secretions.
•Kalium bichromicum 6/8/12x
•Hydrastis 6/8/12x
•Cinnabaris 6/8/12x
GUNA-SINUS (Nose spray)
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GUNA METHOD HORMONAL DISORDERS
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HYPERESTROGENISM
PROGESTERONE D6
HYPOPHYSIS
OVARY
Sensitization of the
hypophyseal
receptors for
progesterone (-)
(-)
Negative feedback
Clinic use of homeopatic Hormones
Decreased hypophyiseal gonadotropins
synthesis
Decreased estrogen synthesis
-
© Dipartimento Scientifico Guna S.p.a.
Clinic use of low dose hormones
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Hormones of PRM • Hypothalamus
– Somatostatine – Beta-Endorphin
• Hypophysis
– FSH – LH – ACTH – Prolactin – TSH
• Pineal Gland
– Melatonin
• Thyroid – TSH – Triiodohyronine (T3) – Thyroxine (T4) – Calcitonin
• Parathyroids – Parathormone (PTH)
• Ovary
– Beta-Estradiol – Progesterone
© Dipartimento Scientifico Guna S.p.a.
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GUNA-FEM
PINEAL GLAND
MELATONIN
HYPOTHALAMUS
HYPOPHYSIS
cAMP
GLANDULA SUPRARENALIS SUIS
THYMUS GLAND
THYROIDINUM
PANCREAS SUIS
–Regulation of thymic hormone synthesis (immune system strengthening)
•Regulation of cortisol and catecholamine synthesis (greater stress resistance).
•Stimulation of sex hormone synthesis
•Regulation of thyroid hormones (irregular under stress conditions)
Stimulation of gonad
function in women
Regulation of insulin response (irregular under
stress conditions)
OOPHORINUM
CORPUS LUTEUM SUIS
LILIUM
NEURO-ENDOCRINE
REPROGRAMMING
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GLANDULA SUPRARENALIS SUIS
THYMUS GLAND
THYROIDINUM
PANCREAS SUIS
–Regulation of thymic hormone synthesis (immune system strengthening)
•Regulation of cortisol and catecholamine synthesis (greater stress resistance).
•Stimulation of sex hormone synthesis
•Regulation of thyroid hormones (irregular under stress conditions)
Stimulation of gonad
function in men
Regulation of insulin response (irregular under
stress conditions)
ORCHITINUM
DAMIANA
NEURO-ENDOCRINE
REPROGRAMMING
© Dipartimento Scientifico Guna S.p.a.
PINEAL GLAND
MELATONIN
HYPOTHALAMUS
HYPOPHISIS
cAMP
GUNA-MALE
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Preliminary data
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Serum Progesterone
(a, b: p< 0.001)
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(a, b: p< 0.05)
Serum Estradiol
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•PROGESTERON D6: 20 drops twice a day from the 14° day to 21° day, for 2-4 months
+ FSH D6: 20 drops twice a day from 1° to 7° day of period for 2-4 months (for the reverse of the relationship LH/FSH) •MELATONIN 4CH: 20 drops at evening every day for 2-4 months
•GUNA LYMPHO: 20 drops at evening every day for 2-4 months
PCO
© Dipartimento Scientifico Guna S.p.a.
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•GUNA-FEM: 20 drops twice a day for 1° month of therapy
continue with
•G3: 20 drops twice a day from the 2° month of therapy
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TSH T4 T3 Interpretazione
Elevato Normale Normale
Ipotiroidismo moderato
(subclinico)
Elevato Basso Basso o normale
Ipotiroidismo
Basso Normale Normale Ipertiroidismo moderato
(subclinico)
Basso Elevato o normale
Elevato o normale
Ipertiroidismo
Basso Basso o normale
Basso o normale
Raro ipotiroidismo ipofisario (secondario)
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HYPOTHYROIDISM
Overweight
with
•GUNA T4 6X
20 drops twice a day over an extended
period of time
Hyperglicemia
with
•GUNA T3 6X
20 drops twice a day over an extended period
of time
•GUNA-Fem/Male
20 drops twice a day over an extended
period of time
•GUNA-Lympho and/or GUNA-
Matrix
20 drops twice a day over an extended
period of time
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HYPERTHYROIDISM
•Somatostatin 4C 20 drops twice a day over an
extended period of time
•Anti IL-1 4C 20 drops twice a day over an
extended period of time
+ •ACTH D6
20 drops twice a day over an extended
period of time
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HASHIMOTO’S
THYROIDITIS
Increase of
IL-6
IL-12
IFN-γ
IL-8
IL-1
Relative deficiency of
IL-10
IL-4
IL-2
Cytokinic structure Autoimmune Thyroiditis
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•IL4 4CH: 20 drops twice a day for 4-6 months
+ •T4 D6: 20 drops twice a day for 4-6 months
+ •T3 D6: 20 drops twice a day for 4-6 months
•GUNA-MATRIX: 20 drops twice a day for 4-6 months
AUTOIMMUNE DISEASES -Hashimoto Disease (TSH over 3 not treated with Eutirox)
•GLANDULA THYREOIDEA SUIS INJEEL: 1 ampoule a week for 4-6 months
Excess of IL17/IL2/IL5/IL6 Low level of: IL4
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METABOLIC SYNDROME
1.Central Obesity
2.High blood pressure
3.High tryglycerides
4.Low HDL-cholesterol
5.Insulin resistance
•25% of Men
•27% of Women
•14.000.000 of italians
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• Cos’è l’insulino-resistenza? In assenza di patologie i livelli di glucosio nel sangue sono mantenuti entro uno stretto intervallo; questo equilibrio è regolato soprattutto dagli ormoni pancreatici: in particolare all’aumento della glicemia si associa l’aumento del trasporto di glucosio nelle cellule ß-pancreatiche con conseguente rilascio in circolo di insulina. L’aumento di insulina a sua volta stimola il trasporto e l’utilizzazione del glucosio da parte dei tessuti periferici (in particolar modo il fegato, i muscoli scheletrici e il tessuto adiposo). Oltre agli effetti sull’omeostasi glicemica, l’insulina regola la crescita cellulare, favorisce la sintesi dei carboidrati, dei grassi, delle proteine e regola infine l’espressione di numerosi geni. L’insulino-resistenza è una condizione caratterizzata da una diminuzione degli effetti biologici dell’insulina; in altri termini, è una condizione nella quale le quantità fisiologiche di insulina producono una risposta biologica ridotta, specie a livello dell’omeostasi glicemica. L’iperglicemia persistente stimola il pancreas a secernere quantità maggiori di insulina, determinando così iperinsulinemia. La resistenza insulinica inoltre modifica il fisiologico metabolismo lipidico determinando un quadro di dislipidemia caratterizzato dall’aumento in circolo di trigliceridi, diminuzione dei livelli di colesterolo HDL e dalla presenza di particelle LDL più piccole e dense (sdLDL), fortemente aterogene. Oltre ad aumentare il rischio trombotico, l’insulino-resistenza determina anche sodio-ritenzione, causando quindi ipertensione arteriosa. L’insulino-resistenza non è di per sé una condizione clinica definita ma contribuisce significativamente alla patogenesi del diabete mellito tipo 2, dell’obesità, della dislipidemia, dell’ipertensione, della statosi epatica non alcolica e della sindrome dell’ovaio policistico (PCOS). Secondo alcuni ricercatori potrebbe esserci un legame tra l’insulino-resistenza ed alcune forme di cancro. Il meccanismo fisiopatologico di questa associazione non è noto. Nel 2001, l’ATPIII (Adult Treatment Panel III) ha definito la sindrome metabolica come “un insieme di fattori di rischio di natura metabolica, connessi all’insulino-resistenza” indicando l’importanza della stessa nello sviluppo della malattia cardiovascolare. Le cause che determinano insulino-resistenza non sono del tutto note. In tutti i casi appare come una realtà multifattoriale in cui pesano sia fattori genetici, inclusi fattori etnici, sia l’inadeguato stile di vita, in particolare una dieta ipercalorica accoppiata ad uno scarso esercizio fisico. Nella maggior parte dei pazienti l’iperinsulinemia compensa la resistenza insulinica anche per diversi anni. Quando la risposta insulinica non è più adeguata alle richiesta si instaura uno stato iperglicemico che può progressivamente evolvere verso il diabete mellito tipo 2.
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METABOLIC SYNDROME INSULIN-RESISTENCE HYPER-INSULINEMIA Cortisolo Stress HYPERGLICEMIA. THE EXCESS OF SUGAR IS TRANSFORMED IN FAT Insulin resistance modifies fat metabolism: INCREASE OF LDL/REDUCTION OF HDL AT LIVER LEVEL
OBESITY HYPERTROPHIC FAT CELLS - cholesterol level increased
- pro-inflammatory stimuli (IL-6, TNF-α)
- fat hyperoxidative processes ATEROSCLEROSYS
Somatostatin 4CH GUNA-MATRIX
Ω Formula/Guna-Liver
SON Formula
Ω Formula
Ω Formula
GUNA- FLAM (IL-10 4CH)
SON Formula T4 D6
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Protective interleukins for Metabolic Syndrome
• Anti IL-1
• IL-4
• IL-10
•GUNA-FLAM
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METABOLIC SYNDROME About Insulin resistance we can do some reasonings. As you know, insulin and GH are realated each other, it means that if you have high levels of GH you increase the amount of insulin in the blood. But we know that with a negative feedback, IGF-1 is able to slowing down the production of GH. So, our IGF-1 4CH could be good. Consider also to slow down GH the use of Somatostatine 4 CH From the point of view of interleukins it is important to reduce the pro-inflammatory ones (IL-6 especially but IL-1 and TNF-alfa also) for instance using the opposite cytokines like IL-10 and IL-4. It is important to drain the matrix because the problem is that insulin molecules don't arrive to the membrane receptor of the the cell's: Guna-Matrix Add Guna-Cell also. Use absolutely Guna-Liver, because you know that insuline resistance provoke an increase of LDL and a deacrease of HDL. Guna-Liver works very well in these conditions. Reduce stress (cortisol mobilize insuline). To control cortisol we can suggest T3 6X to slowing down cortsicosteroids activity And use SON Formula.
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METABOLIC SYNDROME
1.Central Obesity SON Formula/T4 6X
2.High blood pressure Guna-Hypertension
3.High tryglycerides Ω Formula/Guna-Liver
4.Low HDL-cholesterol Ω Formula/Guna-Liver
5.Insulin resistance Somatostatin 4C/Guna-Matrix
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DRAINING CORE
Taraxacum 2X*
Carduus 2X*
Chelidonium 2X**
Ceanothus 6X**
METABOLIC CORE
CONSTITUTIONAL CORE
• Stimulation of hepatic filter
function *.
• Choleretic and cholagogue
activity (direct
hyperbilirubinemia and
icterus)**.
Leptandra 6X*
Chionanthus 6X*
Lycopodium 6X**
Hepar suis 6X***
Gal Bladder 8X***
Pancreas suis 8X***
Spleen 8X***
Jejunum p. 8X***
FUNCTIONAL ACTIVATION
CORE
• Anti-inflammatory and anti-congestive activity on liver and gallbladder*.
• Stimulation of enzymatic function **.
• Stimulation of general function of the liver and organs belonging to the digestive system***
Ac. Fumaricum 4X* Vit. B1/B2/B3/B6/B12 *
Inositol 4X* Cholinum 4X**
Natrium oxalaceticum 4X*** Natrium pyruvicum 4X***
• Triglyceride hydrolysis stimulation and support in forms of hepatic steatosis*, (hereditary) hypercholesterolemia reduction (Inositol especially)*.
• Hepatic damage caused by alcohol**.
• Restoration of metabolic function of the hepatocytes and liver homeostasis***.
Kalium sulfuricum 6/8/12X
Natrium sulfuricum 6/8/12X
• Rebalancing of the
constitutional weakness of
the hepatic subject
GUNA-LIVER
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•OMEOFORMULA 1 1 i.m. injection once a week over an
extended period of time
•GUNA-FEM/MALE 20 drops twice a day over an extended
period of time
GUNA-MATRIX 20 drops twice a day over an
extended period of time
•GUNA-T4 6X 10-20 drops twice a
day over an extended period of time
METABOLIC SYNDROME
•SON Formula 3-5 tablets every
meal
•GUNA-FLAM
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•GUNA-FEM: 20 drops twice a day for 4-6 months
+ •β-ESTRADIOL D6: 20 drops twice a day for 4-6 months
+ •PROGESTERON D6: 20 drops twice a day for 4-6 months, every month from the 14° day of the month
•GUNA-MATRIX: 20 drops twice a day for 4-6 months
•ANTI AGE STRESS: 3-5 pellets 2-3 times a day for 4-6 months (for general neuro-vegetative regulation, Stress conditions)
+ •MELATONIN 4CH: 20 drops at evening every day for 4-6 months (usefull in cases of hyperprolactinemia; opposite action of prolactin)
SECONDARY AMENORRHEA
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•GUNA-FEM: 20 drops twice a day for 4-6 months
+ •FSH D6: 20 drops twice a day for from the 1° to the 5° day of the menstrual cycle for 4-6 months
+ •β-ESTRADIOL D6: 20 drops twice a day from the 5° to the 15° day of the menstrual cycle for for 4-6 months
+ •LH D6: 20 drops twice a day for from the 5° to the 15° day of the menstrual cycle for 4-6 months
+ •PROGESTERON D6: 20 drops twice a day for 4-6 months, every month from the 14° to 24° day of the month
•GUNA-MATRIX: 20 drops twice a day for 4-6 months
•GUNA-VENUS: i dose a day, every day for 2 months. •GUNA-MOOD: 10-20 drops 2-3 times a day for 4-6 months (for cyclic mood instability)
+ •MELATONIN 4CH: 20 drops at evening every day for 4-6 months
HYPOFERTILITY
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•GUNA-FEM: 20 drops twice a day for 4-6 months
+ •CALCITONIN D6: 20 drops twice a day for 4-6 months
•GUNA-MATRIX: 20 drops twice a day for 4-6 months •GUNA BASIC: 1 bag a day, at evening for 1-2 months (alcalynization of the ECM)
•OSTEOBIOS: 20 drops twice a day for 4-6 months
MENOPAUSE DISORDERS (Osteoporosis)
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OSTEOBIOS PATHOGENETIC EVOLUTION OF OSTEOPOROSIS AND RATIONALE
A reduced ovarian function
(typical of the peri-
menopausal phase) and a
consequent estrogenic
deficit affects the
parathyroid function
Without estrogenic
stimulation, the
parathormone alters the
phospho-calcium-
magnesium homeostasis
The Bone releases
calcium as a
consequence of the
activation of
osteoclasts
Onset of
osteoporosis
1
4
3
2
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PARATHYROID GLAND
10/30/200X
modulates the parathyroid
function and limits the
synthesis of
PARATHORMONE
CALCITONIN 6X limits
bone reabsorption and a
reduced level of
parathormone slows down
calcium release from the
bone
Calcium is kept
inside the bone The synergistic
action of BONE,
MAP and the 3
CALCAREE
improves the
hystologic structure
of the bone
1
4
3
2
© Dipartimento Scientifico Guna S.p.a.
OSTEOBIOS PATHOGENETIC EVOLUTION OF OSTEOPOROSIS AND RATIONALE
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Paratyroid gland
Control of parathyroid function and reduction of parathormone synthesis
CALCITONIN
Starter for the synthesis of autologous calcitonin; sensitization of bone cell receptors Modulation of
osteoclast activity.
Stimulation of
osteoblast activity.
MAP
BONE
PORCINE
Substrata and
stimulation of protein
synthesis of bone
matrix
Regulation of
calcium
metabolism
CALCAREACARBONICA
CALCAREA
PHOSPHORICA
CALCAREA FLUORICA
OSTEOBIOS
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•GUNA-FEM: 20 drops twice a day for 2-4 months
+ •LH D6: 20 drops at evening every day for 2-4 months
+ •ACTH D6: 20 drops at evening every day for 2-4 months
+ •SEROTONIN D6: 20 drops at evening every day for 2-4 months •Oxitocine
•GUNA-MATRIX: 20 drops twice a day for 2-4 months
•GUNA-VENUS: 1 dose a day for 2-4 months. •GUNA-MOOD: 20 drops twice a day (mood instability)
LOW LIBIDO (female)
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•GUNA-MATRIX: 20 drops twice a day for 2-4 months
•GUNA-MARS: 1 dose a day for 2-4 months •ANTI AGE STRESS: 3-5 pellets 2-3 times a day for 2-4 months (for general neuro-vegetative regulation, Stress conditions)
+ •MELATONIN 4CH: 20 drops at evening every day for 2-4 months (in case of strong stress only)
LOW LIBIDO (male)
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•GUNA-MALE: 20 drops twice a day for 2-4 months
+ •LH D6: 20 drops at evening every day for 2-4 months
+ •ACTH D6: 20 drops at evening every day for 2-4 months
+ •SEROTONIN D6: 20 drops at evening every day for 2-4 months •Oxitocine, Dopamine, alpha-Melanocite
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PRM
ANTI AGING THERAPIES
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Ivo BIANCHI M.D. ©
ELDERLY People
Low Reactivity
Cell Stimulation
GUNA Cell
Tissue Stimulation
GUNA Matrix
Hormonal Stimulation
GUNA Female/Male
Immune Stimulation
Citomix
High Level of Intoxication
Drainage
Generic
Specific
High Level of Inflammation
Anti Inflammation
GUNA Flam
IL-10
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Trophic effect
Anti aging
Catabolic effect
Anti cancer
Melatonin
T3
Somatostatin
IGF-1
DHEA
GH
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•GUNA-FEM/MALE: 20 drops twice a day for 2-4 months
+ •GUNA-FLAM: 20 drops twice a day for 2-4 months
•MELATONIN 4CH: 20 drops at evening every day for 2-4 months
+ •IGF1 4CH: 20 drops at evening every day for 2-4 months (anti-neoplastic and anti-oxidant action) •IL2 4CH: 20 drops twice a day for 2-4 months (it is the “amti-aging interleukine) •CNTF 4CH: 20 drops twice a day for 2-4 months (brain aging)
•CEREBRUM COMP.: 1 ampoul evry 2 days for 2-4 months (elderly people)
•GUNA-GERIATRICS: 20 drops twice a day for 2-4 months
ANTI AGING GENERAL STRATEGY
•GUNA-MATRIX: 20 drops twice a day for 2-4 months
+ •GUNA-CELL: 20 drops twice a day for 2-4 months
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Matrix liquification
and drainage
Action against toxin
impregnation
Lymphatic drainage
•Stimulation of
mitochondrial energy
production.*
•Matrix acidification
(promoting connective tissue
reactivity).**
•Ac. D-L malicum 6X*
•Natrium oxal. 6X*
•Natrium pyruv. 6X*
•NADID 6X*
•Trychinoil 6X*
•Vit. C 2X*
•Ac. L(+) lacticum3X**
•Deactivation (through
inflammation) and
neutralization of the
impregnated toxins*.
•Synergistic action with
Fucus and thyroid hormone
activating the
sympatheticotonic nervous
system**.
•Pyrogenium 12X*
•Fucus 3X*
•Tyrosine 2X**
•Phenilalanine 2X**
•Histidine 2X**
•Inactive toxins mobilized towards the lymphatic circle for drainage
•Lymphatic vessel 6X
•Matrix hydrolysis*
•Action against the constitutional tendency to impregnation of the matrix with toxins and to the development of Dysmetabolic Mesenchymopathy (psychcosis).**
•Matrix solubilization.***
•Hyaluronidase 6X*
•Thuja 6/8/12/30/200X**
•Natrium sulfuricum 6/8/12/30/200X **
•Prolactine 6X***
•DHEA 6X***
•Increase of Fundamental Substance kinetics (protein hydrolysis, hyper-ionicity, histaminic activity, increased temperature) and matrix turnover rate.*
•Sympatheticotonic stimulation.**
•Vagotonic inhibition.***
•IL 6 4C*
•DHEA 6X* •Pyrogenium 12X*
•Conjunctive Tissue 6X*
•Tyrosine 2X**
•Phenilalanine 2X**
•Histidine 2X**
•Prolactine 6X***
GUNA-MATRIX
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GUNA CELL
Vitamins
Increase of energetic
metabolism.
Coenzyme activity performing catalytic action on cell functions.
Catalytic action on enzyme functions.
• Carrier action*.
• Reprogramming of cell function**.
• 2nd function messenger***.
a-lipoic-ac. 3X
Succinic. ac. 3X
Fumaric. ac. 3X
Methyglyoxal 10X
Vit. E
Vit. C Vit. B1, B2, B3, B5,
B6, B9, B12
Colchicum 6/12/30X
Conium 6/12/30X
Podophyllum 6/12/30X
Methyglyoxal 10X
Anti-degenerative and
anti-aging action.
Ac.-L-carnitine* 2X
DNA** 6X
RNA** 6X
Collinsonia 2X***
cAMP 6X*** Mn-gluc. 3X
Mn-phosph. 6X
Mg-phosph. 3X
P 4X
Ca-gluc. 3X
Fe fumar. 3X
S 3X
Se 3X
Cu sulph. 3X
Zn-gluc. 3X
K-aspart. 3X
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• Modulation of the neurogenic phase of inflammation*.
• Sensitization of the beta-endorphin peripheral receptors**.
• RES stimulation and hindrance to the possible septic progression of the inflammatory process.
The 3 pillars… in a drug
GUNA-FLAM
© Dipartimento Scientifico Guna S.p.a.
Aconitum* Belladonna*
Ferrum phosphoricum* Apis*
Bryonia* Pyrogenium* Phytolacca*
Natrium pyruvicum* Acidum citricum*
Cu-gluconate* Anti IL 1-alfa** TGF 1 beta***
IL 10***
• Modulation of the neurogenic, vasal exudative phases of the inflammatory process*.
• Hindrance to the inflammation start point**.
• Potentiation of the immunologic anti-inflammatory activity having Th2-Th3 polarity***.
Aconitum* Beta-endorphin**
Hepar sulfuris
Pyrogenium
Ferrum phosphoricum
Melatonin 4C
Hypophysis porcine 200X
Pineal Gland 6X
Conjunctive tissue 12X
• Regulation of the extracellular matrix function through the modulation of the hypophysary hormons action and the pineal gland stimulation.
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WHY GUNA GERIATRICS IS THE BASIC REMEDY FOR AGING ?
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Basic Oral anti Aging Remedy: Guna Geriatrics
D6
D3
Suis-Organs
10 pg
NT3 NT4 Melatonin
Hormones Neurotrophins
Plumbum
metallicum
Hepar
Lobo
frontalis
Glandula
suprarenalis
Hypothalamus Baryta
carbonica
Homeopathic Remedies
Phenilalanine
Thyrosine
Oxitocine
TRH
LH-RH
ACTH Acidum
DL-malicum
Catalysts
Acidum
pyruvicum
Hormones
BDNF
Parabenzochinon
Baryum
oxalsuccinicum
Arnica
IGF-1
Aminoacids
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Herbals
(Arnica montana)
Catalysts and aminoacids
Growth factors
Hormones Courtesy from Dr. I Bianchi
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Aging and hormones and cytokines
Courtesy from Dr. I Bianchi
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Anti Aging Hormones
Melatonin Insulin
Growth Factor ACTH
Courtesy from Dr. I Bianchi
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• In animals longlife is correlated with:
–High levels of :
• IGF-1
•Melatonin
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Melatonin and Aging
• Circulating melatonin decreases with age and in recent years much interest has been focused on its immunomodulatory effect.
• Melatonin stimulates the production of progenitor cells for granulocytes-macrophages. It also stimulates the production of NK cells and CD4+ cells and inhibits CD8+ cells.
• The production and release of various cytokines from NK cells and T-helper lymphocytes also are enhanced by melatonin.
• Melatonin presumably regulates immune function by acting on the immune-opioid network, by affecting G protein-cAMP signal pathway and by regulating intracellular glutathione levels.
Melatonin has the potential therapeutic value to enhance immune function in aged people and in patients in immunecompromised conditions.
Courtesy from Dr. I Bianchi
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Insulin Growth Factor-1 and Aging
• Insulin-like growth factors (IGFs) are polipeptides with high sequence similarity to insulin
• IGF-1 is mainly secreted by the liver as a result of stimulation by GH.
• IGF-1 is important for both the regulation of normal physiology, as well as a number of pathological states, including cancer
• IGF axis has been shown to play roles in the promotion of cell proliferation and inhibition of apoptosis
• Factors that are known to cause variation in the levels IGF-1 in the circulation include an individuals genetic make-up, the time of day, age, sex, exercise, stress levels, genetics, nutrition level and body mass index (BMI), disease state, race, estrogen status and xenobiotic intake.
Courtesy from Dr. I Bianchi
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ACTH and Aging
• It was demonstrated that administration of ACTH led to facilitation of learning and strengthening of memory processes (conditioned reflex traces). ACTH promoted strengthening of movement, orientational-investigative, and intersignal activities, produced hyperalgesia, and blocked the effects of naloxone
• ACTH is involved in motivation, learning and memory. • ACTH restores the ability of hypophysectomised rats to acquire an
avoidance response in a shuttlebox.
Courtesy from Dr. I Bianchi
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Anti aging Hormones
Oxitocine TRH LH-RH
Courtesy from Dr. I Bianchi
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Oxitocin and Aging
• Oxytocin is a mammalian hormone that also acts as a neurotransmitter in the brain.
• Oxytocin is released during orgasm in both sexes.
• In the brain, oxytocin is involved in social recognition and bonding, and might be involved in the formation of trust between people, in generosity and in the reduction of fear
• Can impair memory retrieval in certain aversive memory tasks.
Courtesy from Dr. I Bianchi
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TRH and Aging
• The brain tripeptide thyrotropin-releasing hormone (TRH) has been demonstrated to facilitate cholinergic neurotransmission.
• TRH markedly attenuated scopolamine-induced impairment of some measures of memory, most notably on a selective reminding task.
• Cognitive study suggest a facilitatory role for TRH
in human memory processes. • Scientific studies suggest that stimulation of TRH
may be useful for treatment of age-related emotional disorders and memory disturbance in dementia.
Courtesy from Dr. I Bianchi
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LH-RH and Aging • Luteinizing hormone-releasing hormone (LH-RH), the key reproductive
hormone coordinating the major features of mammalian reproduction • The hypothalamic decapeptide can modulate immune functions directly,
through local paracrine–autocrine effects in immune cells, and indirectly through activation of the hypothalamic– pituitary–gonadal (HPG) axis
• LH-RH participates both at central and peripheral levels in the interaction between the neuroendocrine and immune systems.
• The reciprocity of the NEI signalling systems is further supported by the ability of sex steroids to modulate thymus-dependent immune function via direct effects on specific target genes involved in the development of sex-dimorphic immune responses, including the downregulation of the immune response observed during pregnancy.
Courtesy from Dr. I Bianchi
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Basic Oral anti Aging Remedy: Guna Geriatrics
D6
D3
Suis-Organs
10 pg
NT3 NT4 Melatonin
Hormones Neurotrophins
Plumbum
metallicum
Hepar
Lobo
frontalis
Glandula
suprarenalis
Hypothalamus Baryta
carbonica
Homeopathic Remedies
Phenilalanine
Thyrosine
Oxitocine
TRH
LH-RH
ACTH Acidum
DL-malicum
Catalysts
Acidum
pyruvicum
Hormones
BDNF
Parabenzochinon
Baryum
oxalsuccinicum
Arnica
IGF-1
Aminoacids
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Neurotrophins
• Neurotrophic factors are endogenous proteins that alter the survival, development, maintenance, and differentiation of neurons.
• Evidence has indicated that neurotrophic factors may be implicated in the normal functional activity of nerve cells.
• These molecules are generally small, soluble proteins with molecular weights between 13 and 24 kDa and are often active as homodimers (1,2).
Courtesy from Dr. I Bianchi
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Neurotrophins
• Brain Derived Neurotrophic Factor (BDNF) Supports motoneuron development and survival in animals and prevents naturally occurring death
• Neurotrophin 3 (NT-3) NT-3 is related to NGF and has homology with it. It is found in motorneurons, sympathetic neurons and some peripheral sensory organs.
• Neurotrophin 4 (NT-4) NT 4 also is related to NGF and has similar homology. NT-4 is produced in skeletal muscle but production of NT-4 was found to depend on muscle activity
Courtesy from Dr. I Bianchi
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Brain-Derived Neurotrophic Factor (BDNF)
• Acting on certain CNS neurons and on the peripheral nervous system
• Helps to support the survival of existing neurons and encourage the growth and differentiation of new neurons and synapses
• ACTIVE IN THE HYPPOCAMPUS, CORTEX, BASAL FOREBRAIN AREAS VITAL TO LEARNING, MEMORY, AND HIGHER THINKING.
• Although the vast majority of neurons in the brain are formed prenatally, parts of the adult brain retain the ability to grow new neurons from neural stem cells in a process known as Neurogenesis
• Various studies have shown possible links between low levels of BDNF and conditions such as : Depression, Schizofrenia, Obsessive Compulsive Disorders, Alzheimer Disease, Untington’s Chorea, Rett Syndrome, Dementia, Anorexia and bulimia Nervosa
Courtesy from Dr. I Bianchi
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Brain-Derived Neurotrophic Factor (BDNF)
• BDNF is one of the most active neurotrophins. Mice born without the ability to make BDNF suffer developmental defects in the brain and sensory nervous system, and usually die soon after birth, suggesting that BDNF plays an important role in normal neural development
• BDNF is actually found not only in the brain but also in a range of tissue and cell types : Retina, Motor neurons, Kidneys and Prostate.
• Various studies have shown possible links between low levels of BDNF and conditions such as : Depression, Schizofrenia, Obsessive Compulsive Disorders, Alzheimer Disease, Untington’s Chorea, Rett Syndrome, Dementia, Anorexia and bulimia Nervosa
Courtesy from Dr. I Bianchi
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NT-3 : synaptic potentiation NT-4 : synaptic plasticity
Neurotrophin-3 (NT-3) supports the SURVIVAL AND DIFFERENTIATION OF NEURONES IN THE CENTRAL AND PERIPHERAL NERVOUS SYSTEMS through a number of mechanisms that occur in a matter of hours or days. NT-3 may also have a more rapid mode of action that influences SYNAPTIC ACTIVITY IN MATURE NEURONES. NT-3, have been implicated in the regulation of synaptic transmission and plasticity.
Neurotrophin 4 (NT4) is required for the SYNAPTIC PLASTICITY mediating both tolerance and memory. NT4 may be involved in neural plasticity underlying opiate tolerance
Courtesy from Dr. I Bianchi
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Basic Oral anti Aging Remedy: Guna Geriatrics
D6
D3
Suis-Organs
10 pg
NT3 NT4 Melatonin
Hormones Neurotrophins
Plumbum
metallicum
Hepar
Lobo
frontalis
Glandula
suprarenalis
Hypothalamus Baryta
carbonica
Homeopathic Remedies
Phenilalanine
Thyrosine
Oxitocine
TRH
LH-RH
ACTH Acidum
DL-malicum
Catalysts
Acidum
pyruvicum
Hormones
BDNF
Parabenzochinon
Baryum
oxalsuccinicum
Arnica
IGF-1
Aminoacids
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Anti aging Amino Acids
Thyroxine Fenilalanilne
Courtesy from Dr. I Bianchi
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Thyrosine and aging
• Nonessential amino acid synthesized in the body from phenylalanine. As a building block for several important
brain chemicals, tyrosine is needed to make epinephrine, norepinephrine, serotonin, and dopamine, all of which work to regulate mood.
• Deficiencies in this amino acid is associated with depression. • Tyrosine also aids in the production of melanin and in the function of the adrenal, thyroid, and pituitary glands.
Tyrosine is also involved in the synthesis of enkephalins, substances that have pain-relieving effects in the body.
• Low levels of tyrosine have been associated with low blood pressure, low body temperature, and an under active thyroid.
• Because tyrosine binds unstable molecules (called free radicals) that can potentially cause damage to the cells and tissues, it is considered a mild antioxidant. Thus, tyrosine may be useful for people who have been exposed to harmful chemicals (such as from smoking) and radiation.
Courtesy from Dr. I Bianchi
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Phenylalanine and aging
• Phenylalanine is used to treat a variety of medical problems. Because some antidepressants work by raising
norepinephrine levels, phenylalanine has been used to treat depression
• Phenylalanine has been suggested as a treatment for chronic pain caused by rheumatoid arthritis, muscle pain, and osteoarthritis, as it blocks enkephalinase, an enzyme that may act to increase pain levels in the body. There is some evidence to support the use of phenylalanine to alleviate chronic pain
Courtesy from Dr. I Bianchi
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Basic Oral anti Aging Remedy: Guna Geriatrics
D6
D3
Suis-Organs
10 pg
NT3 NT4 Melatonin
Hormones Neurotrophins
Plumbum
metallicum
Hepar
Lobo
frontalis
Glandula
suprarenalis
Hypothalamus Baryta
carbonica
Homeopathic Remedies
Phenilalanine
Thyrosine
Oxitocine
TRH
LH-RH
ACTH Acidum
DL-malicum
Catalysts
Acidum
pyruvicum
Hormones
BDNF
Parabenzochinon
Baryum
oxalsuccinicum
Arnica
IGF-1
Aminoacids
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Suis organs in: GUNA-Geriatrics
Hepar suis
• Supports Digestive and Detoxicatory Functions
Suprarenal suis
• Opposing Age and Stress Related Endocrine disfunctions
Hypothalamus suis
• Resetting of biological clock
Lobus frontalis suis
• Antagonizing cognitive deterioration Courtesy from Dr. I Bianchi
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•GUNA-FEM/MALE: 20 drops twice a day for 2-4 months
+ •MELATONIN 4CH: 20 drops at evening every day for 2-4 months •NGF 4CH: 20 drops at evening every day for 2-4 months (memory disorders) •IL-1 b 20 drops before sleeping
•GUNA AWARENESS: 20 drops twice a day for 2-4 months • GUNA Geriatrics : 20 drops twice a day for up to 6 mounths •GUNA-BRAIN: 1 tablet twice a day for 2-4 months •Progesteron D6 20 drops morning and evening
COGNITIVE FUNCTIONS FAILURE AND MEMORY DISORDERS
•GUNA-MATRIX: 20 drops twice a day for 6-12 months •GUNA-CELL: 20 drops at evening every day for 2-4 months
© Dipartimento Scientifico Guna S.p.a.
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