Physiological Regulating Medicine in Immune and Endocrine … · 2014-05-27 · extra -cellular...

London Saturday October the 6th, 2012

_______________

Physiological Regulating Medicine in Immune and Endocrine Disorders

Alessandro Perra – Scientific Director of GUNA S.p.a.

Save your time!

Take your DIPLOMA of Specialist in

Physiological Regulating Medicine

www.prmacademy.org

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-)

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.

HOMEOSTASIS

DISEASE

DISEASE © Dipartimento Scientifico Guna S.p.a.

P N E I

•T° (inflammation; Immune System)

•pH •O2 •Glycemia

P N E I

PSYCHE

SOMA PSYCHE

P.N.E.I. NETWORK AND MESSENGER MOLECULES

INTERLEUKINS

HORMONES

NEUROPEPTIDES

HORMONES

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

Da: PsicoNeuroEndocrinoImmunologia. Francesco Bottaccioli – RED Edizioni

HPA AXIS

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

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.

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.

HEALTH

PHYSIOLOGICAL CONCENTRATION

DISEASE

HYPO-CONCENTRATION

HYPER-CONCENTRATION

4C – X6

C O P E Cytokines & Cells Online Pathfinder Encyclopedia

Version 26.7 (Spring 2011 Edition)

Messenger Molecules

Quality and Quantity

Not only the right

MESSAGE but also the right “VOLUME”.

TRANS-MEMBRANE RECEPTORS Up- and Down-Regulation

Cell-surface receptor

Soluble TNF receptor

Cell activation

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

The affinity of a receptor for the specific cytokine or the specific hormone is very

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

PROBLEM Is it possible to modulate the

action of interleukines and hormones?

IF DISEASES ARE EXPRESSIONS, CONSEQUENCES OF

CHANGED CONCENTRATION OF MESSENGER MOLECULES…

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.

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

Inflammatory diseases Allergy

THE CONCEPT OF BALANCE – RECIPROCITY of TH CELLS

How to use the messenger molecules

THE SCALES OF THE BODY

Th1 Th2

THE IMMUNE SYSTEM

Clinic use of low dose cytokines

Th-1/Th-2 BALANCE

RHEUMATOID ARTHITIS

ALLERGY

Th1 Th17

Th2 Th3

Th1 UP-REGULATION

Th2 DOWN-REGULATION Th1 DOWN-REGULATION

Th2 UP-REGULATION

Focus on:

Relationship among Th1-Th2-Th3

Th2 Th1

TGF-β DOWN-REGULATES DOWN-REGULATES

Plasticity and Rigidity of

Relationship among Th1-Th2-Th3

Single cytokines

SUPPORTIVE

THERAPY FOR

CANCER

Effects of low dose cytokines (IL-12)

on PBMC of human lung carcinoma

in vitro.

Torino

Accepted on May, 15th 2012 - In press: Journal of Cancer Therapy

IFN-gamma

Th1 IL-12 4C

T citotoxic Lymphocites

T suppressors Lymphocites

Th3 Responsable of immundeficiency during cancer

1.7 1.7

basale CH3 CH4 placebo IL12 10ng/ml

day 10

basale CH3 CH4 placebo IL12 10 ng/ml

Series1 46.7 67.4 69.7 69.9 66.1

CH3 CH4 placebo IL12 10ng/ml

Series1 49.8 66.1 62.6 34.6

Day 10

basale CH3 CH4 placebo IL12 10 ng/ml

Series1 30.7 19 48.4 48.3 4.8

CH3 CH4 placebo IL12 10 ng/ml

Series1 32.8 56 46.2 4.2

Day 10

Da: PsicoNeuroEndocrinoImmunologia. Francesco Bottaccioli – RED Edizioni

HPA AXIS

Effects of low dose cytokines (IFN-gamma) on PBMC of human colon carcinoma in vitro.

Torino –Dipartimento di Fisiopatologia Clinica

Preliminary data

IFN-gamma

NK-cells

Anti cancer activity

IFN-gamma 4C

ACTIVATION OF NK-cells IN CANCER PATIENTS

•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

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

INFLAMMATION

DRAINAGE

HOMEOSTASIS

HOMEOSTASIS INFLAMMATION AND

DRAINAGE

©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

GUNA-MATRIX TH

INFLAMMATION mother of all the diseases

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

EXTRA-

CELLULAR

MATRIX

MEMBRANE

RECEPTORS

VESSELS

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

SOL PHASE

GEL PHASE

INFLAMMATION

’70s

“Inflammation is a stereotyped 6 phases

pathologic process”

1. RELEASE OF INFLAMMATORY MEDIATORS due to nervous

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.

’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.

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.

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.

…in INFLAMMATION

•IL-1 •TNF-α •IL-6 •IL-8

Single cytokines

INFLAMMATION

52 © Dipartimento Scientifico Guna S.p.a.

Interleukin 1 (IL-1) cytokine secreted by macrophages, monocytes, dendritic cells, fibroblasts and endothelial cells.

IL-1 SUPPORTS INFLAMMATORY

PROCESSES

INTERLEUKINE-1 (α; ß)

IL-1 and the cell

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)

CONVENTIONAL DRUGS TO STOP INTERLEUKINE-1 EFFECTS

NSAIDs CORTISON ASA

- - - COX2 PGE2 NO

Low dose SKA-actived Antibody Anti Interleukins -1 (α and β) in Inflammation

Anti IL-1 IL-1

COX2 PGE2 NO

Anti Interleukins-1 (α; ß) act as NSAIDs, cortisone and, in part, as salicylates , without the negative side effects caused by these allopathic medicines.

“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.

CHRONOBIOLOGY of inflammation

Physiological trend

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…

…in INFLAMMATION

Inflammation Cytokines

ANTI-Inflammation Cytokines

•Anti-IL-1 •IL-10 •IL-4 •TGF-β 63

RECOVERING THE BALANCE IN INFLAMMATION

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.

• 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

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.

•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

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.

CHRONOBIOLOGY of inflammation

Pathological trend and restore of physiology through Guna meds

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

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

Focus on

INFLAMMATION

IN AUTOIMMUNE

DISEASES

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

…in Crohn’s disease

•TNF-α •IFN-γ •IL-17 •IL-12 •IL-8

RECOVERING THE BALANCE IN CROHN’S DISEASE

•Anti-IL-1 •IL-10 •(IL-4)

GUT MUCOSA

DIGESTIVE SYSTEM

HOMEOSTASIS

Why G.I. inflammation? -1

Inflammatory Bowel Diseases (IBD)

Ulcerative rettocolitis Crohn’s

Th17 Th1

IL-5 IL-13

Inflammatory Bowel

Diseases

Crohn’s

Disease

Th1/Th17 Mediated

TNF-α

IFN-γ

IL-8 Possibly

Infective causes

Ulcerative Colitis

Th2 Mediated IL-5

Possibly infective causes

Courtesy from Dr. I Bianchi

IMMUNOLOGICAL DIFFERENTIAL DIAGNOSIS (IBD)

• 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

• Involvement of the muscle und serum mucosa

• Focal inflammation with mucosa ulcerations

• Proximal start and distal discontinuous development

Perineal

inflammation

Fistulas formation

Symptomatology

Anatomy

Pathology

Proctoscopic

examination

Localization

Ulcerative colitis Crohn’s disease

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

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

Physiopathology of the mucosal damage in Crohn’s Disease

The intestinal antigen

determines the mucosal

production of IL-6 that inhibits T REG

Macrophage activation

Amplification of the Th1 e Th17

reaction

TNF a IFN g

Conditions of high stress Courtesy from Dr. I Bianchi

…in Crohn’s disease

RECOVERING THE BALANCE IN CROHN’S DISEASE

•Anti-IL-1 •IL-10 •(IL-4)

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

Submitted to: American Journal of Physiology-Gastrointestinal and Liver Physiology

Cytokines levels

Untr DSSDSS+Allop

DSS+4HC OM

DSS+4CH non OM

Untr DSSDSS+Allop

DSS+4HC OM

DSS+4CH non OM

Untr DSSDSS+Allop

DSS+4HC OM

DSS+4CH non OM

Untr DSSDSS+Allop

DSS+4HC OM

DSS+4CH non OM

IL-12* IFN-γ

TNF-α* IL-8

1 2 3 4 5

Cytokines levels

Untr DSSDSS+Allop

DSS+4HC OM

DSS+4CH non OM

Untr DSSDSS+Allop

DSS+4HC OM

DSS+4CH non OM

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

DSS (Dextran Sodium Sulphate) Anti Il-1 4CH + IL-10 4CH

BEFORE TREATMENT AFTER TREATMENT

We can say that

are a modern, effective,

no side effects Anti TNF-α

Guna Anti IL-1 4CH

Guna IL-10 4CH

GUT MUCOSA

DIGESTIVE SYSTEM

HOMEOSTASIS

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

Increase of immune-reactive P substance (visceral neurotransmitter) with inflammatory activity

Increase of pseudoaffective answer (miseaure of visceral pain)

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

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.

• 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

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

lostro

GUT MUCOSA

DIGESTIVE SYSTEM

HOMEOSTASIS

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

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**

ETIOPATHOGENESIS OF INTESTINAL

DYSBIOSIS

ALTERATION OF INTESTINAL MICROFLORA

IMMUNODEFICIENCY

REDUCTION OF INTESTINAL DRAINAGE

INTESTINAL FERMENTATION

AND PUTREFACTION

EUBIOFLOR

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

EUBIOFLOR

•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

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

Cytokines and Symptoms

IL-1 Stimulus

Prostaglandins

TNF Stimulus

Metalloproteinasis

IL-6 Systemic symptoms:

Myalgias

Weight loss

Rheumatoid Arthritis: Cytokinic

structure

Pathogenetic cytokines for the

Osteolysis

TNF-α

Cytokines that inhibit

Osteolysis

GM-CFS

IFN-γ

108 Prof. Ivo BIANCHI

MONOCYTES/

MACROPHAGES

FIBROBLASTS

PROLIFERATION CHONDROCYTES OSTEOBLASTS

INFLAMMATION SYNOVIAL PANNUS

FORMATION

CARTILAGE BREAKDOWNS

BONE RESORPTION

RHEUMATOID ARTHRITIS

IMMUNOLOGICAL HYPERACTIVATION

Pathologic inflammatory status

Inhibitory therapy of hyperexpressed cytokines

Anti IL-1 4C

Physiological anti-inflammatory response

Boosting of this stimulus

TGF-β 4C

•ANTI IL1: 20 drops twice a day for 2-4 months

+ •IL4 4CH: 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

+ •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

Verum Placebo N=15 MEDIA

PASI SCORE A T=0 7,67

DLQI A T=0 5,87

N=15 MEDIA

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

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

DLQI A T=0 8,0

N=14 MEDIA

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

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)

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.

Th2Th1

EXPOSURE SENSITIZATION

ALLERGIC PUZZLE

Th2Th1 REBALANCE

DRAINAGE ASPECIFIC AND SPECIFIC

DE-SENSITIZATION

ALLERGIC PUZZLE

THE THERAPEUTIC AETIOLOGIC SOLUTION

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)

…IN ALLERGY: SWITCH Th1/Th2

•IL-4 •IL-5

ALLERGY

THERAPEUTIC STEPS

DRAINAGE

Th1/Th2 REBALANCE

SPECIFIC AND ASPECIFIC

DESENSITATION

TREATMENT OF

SYMPTOMS

AETIOLOGIC

TREATMENT

SYMPTOMATIC

TREATMENT

•IL-4 •IL-5

ATOPY – SWITCH Th1/Th2– ALLERGIC TERRAINE

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

Th2 Th1

INF-γ, IL-12 IL-4

INHIBITS

STIMULATES STIMULATES

INHIBITS

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

INF-γ 4CH

IL12 4CH

STIMULATES

HINIBITS © Dipartimento Scientifico Guna S.p.a.

Effects of low dose cytokines in treatment of inflammatory pathologies: use in an animal

model of allergic asthma

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

EXPERIMENTAL PROTOCOL

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

100 [I

l) 120

UNTR OVA UNTR OVA

BALF – after treatment with egg albumin and Al (OH)3

Asthma © Dipartimento Scientifico Guna S.p.a.

Legend •1-Untr=healthy mouse •2-OVA=allergic mouse

Untr OVA OVA+Allo OVA+4CH OVA+4CHn OVA+30CH

Level of IL-4 and IL-5 in mice sera on day 7th of treatment

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

Untr OVA OVA+Allo OVA+4CH OVA+4CHn OVA+30CH

Level of IL-12 and INF-γ in mice sera on day 7th of treatment

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

Unit of measurement… …the mystery… that is not a mystery

4CH 1 fg/mouse

we give… …we detect in the blood

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)

Eosinophil numbers in mouse BALF (bronchoalveolar lavage fluid)

on day 20 of treatment

IL-12 versus association of IL-12+IFN-g

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

Untr OVA+100ng/die OVA+4CH din

ma] (p

Safety of clinical use of SKA treated low doses of interleukines

Preliminary datas

•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.

•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-BOWEL: 20 drops twice a day for 2-4 months (especially for allergic asthma)

ALLERGY

THERAPEUTIC STEPS

DRAINAGE

Th1/Th2 REBALANCE

SPECIFIC AND ASPECIFIC

DESENSITATION

TREATMENT OF

SYMPTOMS

AETIOLOGIC

TREATMENT

SYMPTOMATIC

TREATMENT

•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.

Constitutional core

Symptom core

P.N.E.I. core.

Trace elements core

Organ preparation

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

• 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

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

• 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

Aralia racemosa

Ribes n.*

Plantago* Euphorbium*

Allium cepa* Histaminum*

IL 12**

ING-gamma**

+ •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

• 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

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

P.R.M. in RESPIRATORY DISEASES

COLD AND FLU

•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

Prevention and treatment of flu

and cold syndromes

IMMUNESTIMULATION CORE

SYMPTOMATIC CORE

NK Cells Tc Lymphocites

IMMUNESTIMULATION CORE

Subnucleus of Specific Immunity

Gamma-interferon

Subnucleus of Aspecific Immunity

SINERGISM

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).

GUNA-COMPLEX 1

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

ENT PATHOLOGIES

Inflammation

Acute GUNA-FLAM

Recurrent GUNA-SINUS

Nose Spray

Hypertrophy

Sub acute GUNA-LYMPHO

Chronic GUNA-MATRIX

•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

BACTERIAL TONSILLITIS

•GUNA-LYMPHO 10-20 drops twice a day

over an extended period of time (6-7 months)

RECURRENT TONSILLITIS

•GUNA-FLAM 10-20 drops twice a day

•ANTI IL-1 4C 10-20 drops 2-3 times a day for 2 months at least

•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

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.

•Th2 Response

LYMPHATIC ENLARGEMENT

•Th1 Response

RECURRENT INFECTIONS

TONSILLAR HYPERTROPHY

•GUNA-MATRIX 10-20 drops twice a day

•GUNA-LYMPHO 10-20 drops twice a day

•IFN-γ 4C 10-20 drops 2-3 times a day for 2 months at least

ADENOIDS HYPERTROPHY

•GUNA-SINUS Nose Spray

2 spray in each nostril 2-3 times a day for 2 months at

• IFN-γ 4C 10-20 drops 2-3 times a day for 2 months at least

•GUNA-MATRIX 10-20 drops twice a day

•CITOMIX 5-10 pellets twice a day in acute phase (10-15 days)

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**

•Histidine 2X**

•Prolactine 6X***

GUNA-MATRIX

•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

•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

•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

• 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**

SINUSITIS • Two types of inflammation occur in sinusitis, contributing variably to the

clinical expression of disease.

CHRONIC SINUSITIS

Allergic component

Infectious component

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

• IL-2 4C 10-20 drops 2-3 times a day for 2 months at least

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)

GUNA METHOD HORMONAL DISORDERS

HYPERESTROGENISM

PROGESTERONE D6

HYPOPHYSIS

Sensitization of the

hypophyseal

receptors for

progesterone (-)

Negative feedback

Clinic use of homeopatic Hormones

Decreased hypophyiseal gonadotropins

synthesis

Decreased estrogen synthesis

Clinic use of low dose hormones

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

GUNA-FEM

PINEAL GLAND

MELATONIN

HYPOTHALAMUS

HYPOPHYSIS

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

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

PINEAL GLAND

MELATONIN

HYPOTHALAMUS

HYPOPHISIS

GUNA-MALE

Preliminary data

Serum Progesterone

(a, b: p< 0.001)

(a, b: p< 0.05)

Serum Estradiol

•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

•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

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)

HYPOTHYROIDISM

Overweight

•GUNA T4 6X

20 drops twice a day over an extended

period of time

Hyperglicemia

•GUNA T3 6X

20 drops twice a day over an extended period

of time

•GUNA-Fem/Male

period of time

•GUNA-Lympho and/or GUNA-

Matrix

period of time

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

+ •ACTH D6

period of time

HASHIMOTO’S

THYROIDITIS

Increase of

IFN-γ

Relative deficiency of

Cytokinic structure Autoimmune Thyroiditis

+ •T4 D6: 20 drops twice a day for 4-6 months

+ •T3 D6: 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

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

• 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.

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

GUNA- FLAM (IL-10 4CH)

SON Formula T4 D6

Protective interleukins for Metabolic Syndrome

• Anti IL-1

• IL-4

• IL-10

•GUNA-FLAM

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.

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

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

• 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

•OMEOFORMULA 1 1 i.m. injection once a week over an

•GUNA-FEM/MALE 20 drops twice a day over an extended

period of time

GUNA-MATRIX 20 drops twice a day over an

•GUNA-T4 6X 10-20 drops twice a

day over an extended period of time

METABOLIC SYNDROME

•SON Formula 3-5 tablets every

•GUNA-FLAM

•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

•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

+ •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-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

+ •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)

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

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

Calcium is kept

inside the bone The synergistic

action of BONE,

MAP and the 3

CALCAREE

improves the

hystologic structure

of the bone

OSTEOBIOS PATHOGENETIC EVOLUTION OF OSTEOPOROSIS AND RATIONALE

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.

PORCINE

Substrata and

stimulation of protein

synthesis of bone

matrix

Regulation of

calcium

metabolism

CALCAREACARBONICA

CALCAREA

PHOSPHORICA

CALCAREA FLUORICA

OSTEOBIOS

+ •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-VENUS: 1 dose a day for 2-4 months. •GUNA-MOOD: 20 drops twice a day (mood instability)

LOW LIBIDO (female)

•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)

•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

ANTI AGING THERAPIES

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

Trophic effect

Anti aging

Catabolic effect

Anti cancer

Melatonin

Somatostatin

•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-CELL: 20 drops twice a day for 2-4 months

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**

•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**

•Histidine 2X**

•Prolactine 6X***

GUNA-MATRIX

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

Ca-gluc. 3X

Fe fumar. 3X

Cu sulph. 3X

Zn-gluc. 3X

K-aspart. 3X

• 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

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.

WHY GUNA GERIATRICS IS THE BASIC REMEDY FOR AGING ?

Basic Oral anti Aging Remedy: Guna Geriatrics

Suis-Organs

NT3 NT4 Melatonin

Hormones Neurotrophins

Plumbum

metallicum

frontalis

Glandula

suprarenalis

Hypothalamus Baryta

carbonica

Homeopathic Remedies

Phenilalanine

Thyrosine

Oxitocine

ACTH Acidum

DL-malicum

Catalysts

Acidum

pyruvicum

Hormones

Parabenzochinon

Baryum

oxalsuccinicum

Arnica

Aminoacids

Herbals

(Arnica montana)

Catalysts and aminoacids

Growth factors

Hormones Courtesy from Dr. I Bianchi

Aging and hormones and cytokines

Anti Aging Hormones

Melatonin Insulin

Growth Factor ACTH

• In animals longlife is correlated with:

–High levels of :

• IGF-1

•Melatonin

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.

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.

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.

Anti aging Hormones

Oxitocine TRH LH-RH

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.

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.

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.

Suis-Organs

NT3 NT4 Melatonin

Plumbum

metallicum

frontalis

Glandula

suprarenalis

Hypothalamus Baryta

carbonica

Phenilalanine

Thyrosine

Oxitocine

ACTH Acidum

DL-malicum

Catalysts

Acidum

pyruvicum

Hormones

Parabenzochinon

Baryum

oxalsuccinicum

Arnica

Aminoacids

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).

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

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

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

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

Suis-Organs

NT3 NT4 Melatonin

Plumbum

metallicum

frontalis

Glandula

suprarenalis

Hypothalamus Baryta

carbonica

Phenilalanine

Thyrosine

Oxitocine

ACTH Acidum

DL-malicum

Catalysts

Acidum

pyruvicum

Hormones

Parabenzochinon

Baryum

oxalsuccinicum

Arnica

Aminoacids

Anti aging Amino Acids

Thyroxine Fenilalanilne

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.

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

Suis-Organs

NT3 NT4 Melatonin

Plumbum

metallicum

frontalis

Glandula

suprarenalis

Hypothalamus Baryta

carbonica

Phenilalanine

Thyrosine

Oxitocine

ACTH Acidum

DL-malicum

Catalysts

Acidum

pyruvicum

Hormones

Parabenzochinon

Baryum

oxalsuccinicum

Arnica

Aminoacids

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

•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

Physiological Regulating Medicine in Immune and Endocrine … · 2014-05-27 · extra -cellular...

Documents

Human Protease/Protease Inhibitor Array Kit · as cancer. The Human Protease/Protease Inhibitor Array is a rapid, sensitive, and economical tool to simultaneously detect protease

Year 9 Human Biology Mastery Matrix › uploaded › ... · 4.4 Link carbohydrase (amylase), protease, lipase & bile to the breakdown of particular food groups, identifying where

Acid Hydrolysis

39045286 Protease Papain

DIAZONIUM SALTSspiroacademy.com/pdf-notes/study-meterials/Chemical/...(1) Hydrolysis (a) Hydrolysis of cyanides: complete hydrolysis Partial hydrolysis (b) Hydrolysis by isocyanide

2018 Hydrolysis Redox kb regulatedforprintesisresearch.org/Uploads/Documents/2018_hydrolysis_redox_kb_4slide.… · 19.02.2018 2 •hydrolysis in h+medium •hydrolysis in oh‐medium

Starch Hydrolysis

Condensation & Hydrolysis

Optima of Trypsin-Catalyzed Hydrolysis and Its Inhibition ... · As a protease produced mainly in animals, trypsin is an important digestive enzyme. So far trypsin is diffusely applied

Hydrolysis with Cucurbita ficifolia serine protease reduces antigenic ... · 1 3 DOI 10.1007/s00726-015-2013-2 Amino Acids (2015) 47:2335–2343 ORIGINAL ARTICLE Hydrolysis with Cucurbita

Protease alcalina

Protease-Catalyzed Oligomerization of Hydrophobic Amino ...homepages.rpi.edu/~grossr/literature/8. protease-catalyzed oligomerization.pdf · Protease-Catalyzed Oligomerization of

Protease enzymes

Protease Phylogeny

Protease s

Serine protease

Alkaline protease

A serine-type protease activity of human lens βA3-crystallin is … · 2010. 11. 1. · released p-nitroaniline (yellow) on its hydrolysis by βA3-protease, which was monitored at

Monitoring and simulations of hydrolysis in epoxy matrix

Fundamental Principles of Biogas Product - ijser.in.pdf · is catalyzed by protease. The amide on hydrolysis yield carboxylic acid and an amine. The carboxylic acid gains the OH-