Claire Haresnape Shorter Version (3)

1© Claire Haresnape

HomotoxicologyClaire Haresnape

Research Student, Registered Homotoxicologist

�


Agenda

• A little about me• What is homotoxicology?• What evidence exists?• A different kind of remedy. • The importance of the ECM.• New scientific techniques that cast

light on possible mechanisms of action• Issues of trial design


Claire Haresnape

• Biology Graduate• Science and Art background• Homeopathy/Homotoxicology Training• Practicing 10 years• Research Project at Barts and The

London


PhD

• PhD project centres around the use of homotoxicology to treat female infertility (WHO Class II)

• Hypothesis that using homotoxicology will allow lower doses of ovulation induction agents to be given

• Improve fertility outcomes


1796

1952

1994

HOMEOPATHY BIRTH

H.H. RECKEWEG ENUNCIATES THE HOMOTOXICOLOGIC

PRINCIPLES

IN ITALY ORIGINATES THE PHYSIOLOGICAL

REGULATING MEDICINE (GUNA Method)

New acquisitions about Psycho-Neuro-Endocrino-Immunology outline innovative scenarios in

Homeopathy

New interpretation of the homeopathic principles from an immunologic and biochemical point of view

From homeopathic empiricism to

homotoxicologic scientific nature

Overcoming of the mostly organicistic and

mechanistic (homotoxin-homotoxicosis) vision of

Homotoxicology

© Dipartimento Scientifico Guna S.p.a.5


What from HOMOTOXICOLOGICAL PHARMACOLOGY for the P.R.M. THERAPEUTIC STRATEGY?

Catalysts

Nosodes

Suis organ preparations

METABOLIC STIMULI

FUNCTION REGULATION

IMMUNE STIMULI

© Dipartimento Scientifico Guna S.p.a.


P.N.E.I.

A) REGULATION OF THE NEURO-ENDOCRINE

HOMEOSTASIS

B) RESTORATION OF THE IMMUNOLOGIC EFFICIENCY

•HOMEOPATHIC HORMONES

•NEUROPETIDES•“Suis” organ preparations

•Nosodes

•CYTOKINES•New immunostimulating

substances

ESSENTIAL POINTS OF THE THERAPY


What from:

7


Homotoxicology

• A review of RCT was carried out by Ernst in 2003

• Published in the Eur J Clin Pharmacol 2004

• He concluded that the trials failed to demonstrate the efficacy of this therapeutic approach


Werner Frase

• VP of Int Soc Homotoxicology• Responded in Eur J Clin Pharmacology

2005• Questioned the exclusion of 5 RCT

trials• Homotoxicology is in the process of

being updated and modernised• Questions the conclusion of the review


Since then...

• A group of Italian and European doctors exploring the use of homeopathic doses of biological molecules such as Neuropeptides, Hormones, Cytokines and Growth Factors

– With the support of GUNA S.p.a. –• A new common ground is emerging –• Recent achievements in the field of Psycho-

Neuro-Endocrine-Immunology (P.N.E.I.) • Created a climate for innovation


www.guna.it/research

• Clinical trial on Eubioflor 1 and Mycox effectiveness in the treatment of dysbiosis.

• Treatment of wrinkles and skin slackening using the intradermal injection of a complex homeopathic remedy (Made Omeo Wrinkle). Results of a cohort clinical study on 681 patients.

• Transfactor 11 in HPV viral pathologies (160 cases) • Melatonin. Clinical trial of homeopathised melatonin in

40 cases. • Guna Flu prevention of upper respiratory infections in

paediatrics. A controlled, multicentre clinical trial. • Clinical report on the effectiveness of Guna Throat

http://www.gunainc.com/C_Common/Download.asp?file=/doc/upload/EUBIOFLOR_MICOXOK.pdf

http://www.gunainc.com/C_Common/Download.asp?file=/doc/upload/MADEOK.pdf

http://www.gunainc.com/C_Common/Download.asp?file=/doc/upload/TRANFACTOROK.pdf

http://www.gunainc.com/C_Common/Download.asp?file=/doc/upload/Melatonin.pdf

http://www.gunainc.com/C_Common/Download.asp?file=/doc/upload/GUNA FLU.pdf

http://www.gunainc.com/C_Common/Download.asp?file=/doc/upload/GUNA THROAT.pdf


Research Topics• The experimental use of G-CSF in immunobiotherapy (Study of 33 clinical cases on the use

of Granulocyte Colony-Stimulating Factor (G-CSF) in homeopathic dilution)• Homeomesotherapy for Pain Management in primary chronic coxarthrosis with a

Homeopathic Injectable Formulation (Result of a cohort, randomized, controlled clinical trial)

• Functional and iatrogenic secondary corticohypothalamic amenorrhea in P.N.E.I. Dynamics• Polyglucosamine - action on oxidised lipids and dyslipidemias.• Treatment of allergic manifestations with Transfer Factor (TF). • The matrix tetrametric code: hormones, cytokines, neuropeptides, melatonin.• Preliminary reports on complex homeopathic therapy in patients suffering from post-

menopausal osteoporosis. • The use of cytokines in Homeopathy. The fractal dynamics at the root of our bodies

functioning. • Homotoxicology and basic regulation: Bystander reaction therapy.• The importance of oxidative stress as a risk factor for morbidity.• Homeopathic immunomodulators: principles and clinical cases. The informative role of

cytokines in fractal dynamics.• The role of food intolerance in the pathogenesis of atopic dermatitis.

http://www.gunainc.com/C_Common/Download.asp?file=/doc/upload/1Malzac.pdf

http://www.gunainc.com/C_Common/Download.asp?file=/doc/upload/1Malzac.pdf

http://www.gunainc.com/C_Common/Download.asp?file=/doc/upload/2Milani.pdf



http://www.gunainc.com/C_Common/Download.asp?file=/doc/upload/3Ferranti.pdf

http://www.gunainc.com/C_Common/Download.asp?file=/doc/upload/4Cornelli.pdf

http://www.gunainc.com/C_Common/Download.asp?file=/doc/upload/5Conti.pdf

http://www.gunainc.com/C_Common/Download.asp?file=/doc/upload/6Turco.pdf

http://www.gunainc.com/C_Common/Download.asp?file=/doc/upload/Sanseverino.pdf

http://www.gunainc.com/C_Common/Download.asp?file=/doc/upload/Sanseverino.pdf

http://www.gunainc.com/C_Common/Download.asp?file=/doc/upload/Citokines.pdf

http://www.gunainc.com/C_Common/Download.asp?file=/doc/upload/Citokines.pdf

http://www.gunainc.com/C_Common/Download.asp?file=/doc/upload/mb_ing_04_1_01.pdf






Publications since 2004

• Homotoxicological remedies vrs desmopressin vrs placebo in the treatment of enuresis: a randomised, double-blind, controlled trial– Pietro Ferrara, Giuseppina Marrone, Valentina

Emmanuele, Alessandro Nicoletti, Antonio Mastrangelo, Eloisa Tiberi, Antonio Ruggiero, Alfonso Fasano, Fabrizia Paolini Paoletti

– Pediatr Nephrol (2008) 23:269-274


Conclusion

– 151 children randomised – Homotoxicology shown to be superior to

placebo (P<0.0001) with regard to the number of children attaining 14 consecutive dry nights during treatment

– Homotox shown to be safe and effective even if it is significantly less effective than desmopressin in this clinical condition


Mercurius Heel

• Nickel Gluconate-Mercurius Heel-Potentised Swine Organ Preparations: a new therapeutical approach for the primary treatment of pediatric ranula and intraoral mucocele

• Salvatore Garofalo, Vito Briganti, Sebastiano Cavallaro, Ernesto Pepe, Marina Prete, Liana Suteu, Paolo Tavormina

• International Journal of Pediatric Otorhinolaryngology (2007) 71, 247-255


Conclusions

• This preliminary study evaluates the effectiveness of Nickel Gluconate-Mercurius Heel-Potentised Swine Organ preparations as the primary treatment of Pediatric ranula and intraoral mucocele

• 18 children treated• 89% ranulas and 67% labial mucoceles

completely responded to the therapy• Therapy was shown to be an effective primary

treatment .


Belladonna/Echinacea

• Effects of Atropa belladonna and Echinacea angustifolia in homoeopathic dilution on experimental peritonitis

• C.M.V. Pedalino, F.F. Perazzo, J.C.T. Carvalho, K.S. Martinho, C.de Massoco, and L.V Bonamin

• Homeopathy, Volume 93, Issue 4, October 2004. Pages 193-198


Conclusion

• Belladonna and Echinacea are used in homotoxicology as modulator of inflammatory processes

• Evaluates their effects on leukocyte migration and macrophage activity induced by experimental peritonitis in vivo (mice)

• Found to modulate peritoneal inflammatory reactions and have a cytoprotective effect on leukocytes


Molecules of emotion

• Candace B Pert PhD• Journal of Immunology 1985• ‘A major conceptual shift in neuroscience has

been wrought by the realisation that brain function in modulated by numerous chemicals in addition to classical neurotransmitters. Many of these informational substances are neuropeptides, originally studied in other contexts as hormones, gut peptides or growth factors.’


The birth of PNEI

• ‘Neuropeptide receptors occur on mobile cells of the immune system....Neuropeptides and their receptors thus join the brain, glands, and immune system in a network of communication between brain and body, probably representing the biochemical substrate of emotion.’


PRM

• Restoring physiology through communicating molecules such as hormones, interleukines, neuropeptides and growth factors

• Prepared in homeopathic dilutions, which are the same physiological concentration as the body.

1© Claire Haresnape22

TM

10-3

10‐6

10‐15

10-30

MINIMAL EFFECTIVE PHARMACOLOGICAL DOSE

TOXIC CONCENTRATIONmg/ml

PHARMACOLOGICAL CONCENTRATIONmcg/ml

PHYSIOLOGICAL CONCENTRATIONng‐pcg/ml

ULTRA LOW DOSE CONCENTRATION

TOXIC EFFECT

SIDE EFFECTS

WITHOUT DYNAMIZATION: NO BIOLOGICAL

EFFECTS

PHARMACOLOGICAL EFFECTS

WITH DYNAMIZATION: BIOLOGICAL/PHYSIOLOGICAL

EFFECTS

NO BIOLOGICAL

EFFECTS WITH OR WITHOUT

DYNAMIZATION

EFFECTS OF DIFFERENT DOSES OF CYTOKINES

MINIMAL EFFECTIVE PHYSIOLOGICAL DOSE



• Aconitin 10-5 M Fibrillation

• Aconitin 10-7 M Bradycardia

• Aconitin 10-18 M No effect on healthy heart

Rythm normalization on preintoxicated heart

Aconitin experimentation Pennec, J.P., Aubin, M (1984) – Effect of Aconitum and Veratrum

on the isolated and perfused heart of the common eel. Comp. Biochem, Physiol. 776:367.

Different effects of Aconitin concentrations on isolated and perfused eel heart:

X5

X7

X18



HOMEOPATHICALLY DILUTED HORMONE

Sensitization of receptors (Backup

receptors)

ADENYL CYCLASE ACTIVATION

CAMP ACTIVATION



Low Doses

• The response of a cell to a messenger depends on the number of receptors occupied.

• A typical cell may have about 1000 receptors.

• Only a small fraction (10%) of the receptors need to be occupied to get a large (50%) response.

25© Dipartimento Scientifico Guna S.p.a.


Mechanism of Action

• Sensitization or activation of some units of cellular or plasmatic receptors

• 10-6 (microgramm) or 10-9 (nanogramm) for the cytokines and 10-12 (picogram) for the hormones

• Restoration of autoregulatory homoeostatic mechanism.

• Source: Guna Scientific Department


Malzac and Melatonin

• Malzac J. La melatonina –Sperimentazione clinica su 40 casi della melatonina omeopatizzata

• La Med Bio Suppl al No 3/1995 23-25Investigates the use of melatonin 4CH in 140 patients presenting with various pathologies

• Pathologies including depression• Reports clinically ‘encouraging’ results


Micro Autoradiography

• W.E Stumpf (2005) • J of Pharmacol and Toxicological methods 51 (2005)

25-40• Drug localization and targeting with

receptor microscopic autoradiography• Low dose substances interact with the

cell nucleus• Higher concentrations trigger a cellular

response at cytoplasmic level


Hormesis

• Low dose stimulatory effects of toxic compounds

• Studies require attention to detail, patience and high resolution-high sensitivity approaches

• Valuable information can be gained with micro autoradiography

• With radiolabeled compounds of high specific activity target sites of low dose deposition and action can be identified


Nuclear receptor binding

• With near physiological doses nuclear receptor binding could be well recognised

• With elevated doses, nuclear uptake became saturated and extra nuclear deposition increased

• Due to initial binding and saturation of primary sites


James L. Oschman

• PhD, biophysics and biology• Research at different

universities• In depth research on the

peculiaritiesof the matrix, more precisely the energetic aspects

• Modern research on living matrix andhis scientific base for complementaryholistic medicine

31

Presenter

Presentation Notes

Oschman has both the academic credentials and the background in alternative therapies to carry out his explorations. He has degrees in Biophysics and Biology from the University of Pittsburgh. He has worked in major research labs around the world. These include Cambridge University in England, Case-Western Reserve University in Cleveland, Ohio, the University of Copenhagen, Northwestern University in Evanston, Illinois, where he was on the faculty, and the Marine Biological Laboratory in Woods Hole, where he was a staff scientist. His many scientific papers have been published in the world's leading journals.


James L. Oschman

• Extra-cellular matrix

• Intra-cellular matrix (cytoskeletonand other structures)

• Nuclear matrix

32

J. Oschman

Presenter

Presentation Notes

According to Oschman the living matrix is present at three levels, fading into each other. There is the environment of the cell, called the extra-cellular matrix, full of collagen, elastin, proteoglycans and glycosaminoglycans. There is the intra cellular matrix, representing the cytoskeleton. And finally in the centre of the cell there is the nuclear matrix. Although most toxins will be present and stored in the extracelluar matrix, their influence is often intra cellular and nuclear. For this reason we can‘t see the extra-cellular matrix as an isolated autonome interactive and informative structure but have to stay focused on the interactions between the different ‘levels’ of matrix in the living matrix


Hartmut Heineborn 1941

• Histologist• Histological preparation of

an acupuncture point (1987)• Further research on ECM, especially

on proteoglycans and glucosaminoglycans• Basic research on autoregulatory processes

in ECM• Immunological Bystander Reaction as

a possible working mechanism behind antihomotoxic medications (IBR)

Presenter

Presentation Notes

The German histologist, Prof. H. Heine did a lot of scientific research in biological medicine. He was the first to describe an acupuncture point in histological way after some microscopic observations of histological preparations. He brought complementary medicine a broad knowledge on the microscopic structure of the ECM that he described in detail in different publications. Thanks to the work of Heine we better understand the regulating processes in the ECM. In the inflammation process he proved in full blood cultures that micro dosages of organic material (plants, suis organ extracts) can trigger an immunological bystander reaction. Over motif formation on regulating Th-3 cells, pro inflammatory Th-1 and Th-2 cells are inhibited by the release of TGF-β.


Synonyms of the ECM

• The terrain: Claude Bernard• The mesenchyme: old regular terminology• Connective tissue: old regular terminology (histological) without

any physiological value• The Ground Regulating System (GRS): Pischinger• The Basic Bio Regulating System (BBRS): Lamers, Van Wijk and

Linnemans• The Extra-Cellular Matrix (ECM): current terminology• The Living Matrix: new terminology in complementary medicine

thanks to the work of James Oschman

Presenter

Presentation Notes

In literature a lot of synonyms are used to point at the same system. In fact, ‘extra-cellular matrix’ (ECM) is the only correct scientific term. The others mentioned on the slide above are synonyms that have been used by certain authors. Although BBRS is the most correct term to name and define the function of the ECM it is porely used and certainly not internationally accepted. ECM is the current terminology and should be overall used.


Histology of the ECM

• The ECM is built up like a 3-dimensional network

• Apart from the proteoglycans and glucosaminoglycans, the collagen, elastin and other basic fibers, it contains capillaries, lymphatic and nerve ends, defense cells and basal membranes

• It is present all over the organism and is the main pathway for vicariation

Presenter

Presentation Notes

Conclusion: The extracellular matrix is a three dimensional web-like structure, surrounding in any dimension the organ cells. His structure is made in such a way it can fulfil his physiological task of biophysical filter. The main components of the ECm are collagen, elastin, proteoglycans and glycosaminoglycans. The ECM is the place where arterial capillaries ends and venous capillaries begins. Also the lymphatic system collects his content out of the ECM and is by this a parallel system transporting system of the venous one. Nerves ends and begins in the ECM, triggering with nerve signals or collecting information. All over between this different compounds and structures defence cells like macrophages and mast cells are present to take care, cleanse and defend the organism. As homotoxins can travel over the ECM to other locations, the matrix becomes the main pathway for disease and health evolutions.


ECM

• The ECM is the transmitter area and main area of action of mediators in the human body

• It is part of the living matrix and not to be seen as a separate communication system

• It is the terrain where the organism deals with homotoxins in inflammatory or storage pathways

• The ECM guarantees the quality of life of the cell and is therefore crucial for the organ function

Presenter

Presentation Notes

To take awayfrom this lecture: The ECM is the transmission are for many substances that travel from bloodstream to cell and vice versa. It is also the main terrain of interaction between the different regulation systems. The ECM is also the main area where homotoxins will be stored (deposition phases) or will be eliminated by inflammatory processes (inflammation phases). As direct micro-environment of the cell, the ECM guarantees under normal conditions the life quality of the cell. The ECM is therefore crucial for cell surviving and is a main terrain of action for biological medical therapies. In the ECM present or stored homotoxins will disturb in minor or major degree the cell function and should therefore be avoided at any time to keep the organism in full health.


Chronicdisease

ECMintoxication

Cellhypoxia

Celldysfunction

Physiologicaldisruption

Cellintoxication

Homotoxins

Presenter

Presentation Notes

The cascade of the origin of a chronic disease goes over an ECM intoxication that causes a cell hypoxia. It is a question of time before the cell gets intracellular intoxicated or dysregulated and shows serious dysfunction. The more cells in the same tissue that are concerned, the more physiological disruption will be present in the tissue function. As there is more or less a long term physiological fall out installed, a chronic disease is born.


THE CONNECTIVE TISSUE (sec. Physiological Regulation Medicine)

Morpho-functional unity: vessel-matrix-membrane receptor

MATRIX

MEMBRANE RECEPTORS

VESSELS



Cytokines

• Biological response is achieved with the occupation of a minimal quantity of receptors

• 1%-2% for IL-1• With characteristically low-dose and

low titred physiological dilutions below Avogadro’s Number– Source: L Milani Inflammation and

Physiological Regulating Medicine (2007)


The concept of BALANCE and the use of the cytokines.

Talking about cytokines it’s useful to talk about BALANCE, in particular of balance Th1-Th2.

In case of pathologies there is an imbalance; for example, in the acute inflammatory pathologies the Th1 scale pan is heavier: in

these cases the therapy should make heavier the Th2 (IL4, IL10, TGF -beta) scale pan in order to redress the balance.

On the contrary, in the allergic pathologies the Th2 scale pan isheavier: in these cases the therapy should make heavier the Th1

(IL12, INF -gamma) scale pan in order to redress the balance.

The appropriate “rebalancing” cytokines will play their role workingon the cell receptors.



Th17 cells in Inflammatory Conditions

• Anne Cook has produced a short review• CD4+ T cells have been subdivided into

different subsets largely on the basis of the cytokines they produce.

• Th17 cells produce IL-17• New studies have recognised the role of

Th17 cells in inflammatory conditions such as arthritis and inflammatory bowel disease


• Elevated levels of IL-17 have been detected in rheumatoid synovium and associated with MS, psoriasis and systemic lupus erythematosis.

• The role of Th17 in mediating autoimmune disease is being researched

• Previously it was thought that these were Th1 mediated diseases.


New Therapy??

• IL-12 regulates Th1• IL-4 regulates Th2• TGF-Beta and IL-6 are required for

Naive CD4+ cells to differentiate into Th17 cells

• This differentiation is facilitated by the absence of INF-Gamma and IL-4


Th0

Th1 Th3 TReg Th2 Th17

IL1, INF‐γ, IL2, TNF‐α, IL6, IL8, IL12

IL 10, TGF‐βIL4, IL5, IL6, IL9, IL10, IL13, IL 17

Autoimmunity Trigger

IL 10, TGF‐β

AUTOIMMUNE PATOLOGIESIn autoimmune pathologies it is generally possible to detect low levels of INF-γ e IL4; since these interleukines don’t stimulate the Th0 to differentiate into Th1 or Th2, enable the IL6 to stimulate the Th17 to produce IL17, the real trigger interleukine in autoimmune diseases. According with PRM it’s important tu use opposite citokines; therefore, to slow down the IL6 it is important to use IFN-γ 4CH e IL4 4CH

The central role of Th17 and IL23 and IL17 in autoimmune diseases

From: The Review of Diabetic Studies (2006) 3:72‐75© Dipartimento Scientifico Guna S.p.a.


Th0

Th2Th1

IL1, INF‐γ, IL2, TNF‐α, IL6, IL8, IL12

IL4, IL5, IL6, IL9, IL10, IL13,TGF‐β

INHIBITION

INHIBITION

INDUCTIONINDUCTION

THE CONCEPT OF BALANCEThe cytokines in a cell population stimulate the secretion of the same cytokines and the differentiation of other T helper lymphocytes in the same way.At the same time, Th1 cytokines inhibit the function and the reproduction of Th2 lymphocytes and vice versa

45© Dipartimento Scientifico Guna S.p.a.


THE BALANCE TH1-TH2

TYPICAL SITUATION IN

CASE OF ALLERGY

TIPICAL SITUATION IN CASE OF ACUTE INFLAMMATION




GCSF

IL1

IL2

INF-gammma

IL6

IL8

TNF-alfa

IL12

IL10

TGF beta

IL4

IL5

IL6

IL7

IL9

IL13

47

Th3

TOLERANCE

TGF-β

IL10

Th1 Th2

PRO

INFLAMMATORY

ANTI

INFLAMMATORY



CYTOKINE

THE USE OF CYTOKINES according to PRMSTRENGTHENING SLOW-DOWNING

OPPOSITE CYTOKINE

GCSF GCSF 4CH IL 10 4CH/IL 4 4CH

INF alpha/gamma INF alfa/gamma 4CH IL 4 4CH

IL 1 IL 1 4CH Anti IL 1 4CH/IL 10 4CH

IL 2 IL 2 4CH IL 11 4CH


IL 4 IL 4 4CH INF alfa and gamma 4CH/IL 12 4CH

IL 5 IL 5 4CH TGF-beta 4CH

IL 6 IL 6 4CH Acute inflammation:IL4 4CH/INF-γ 4CH

Chronic inflammation: IL 6 4CHIL 7 IL 7 4CH IL 10 4CH/ TGF-β 4CH

IL 8 IL 8 4CH IL 10 4CH/FGF 4CH


IL 10 IL 10 4CH IL 1 4CH/TNF-alfa 4CH/IL 6 4CH


IL 12 IL 12 4CH IL 4 4CH/IL10 4CH

TGF-beta TGF-beta 4CH IL 5 4CH/IL 7 4CHTNF-alpha Tnf-alfa 4CH IL 6 4CH/IL12 4CH/IL 4 4CH48

© D

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ento

Sci

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•Rheumatoid Arthritis (IL1, IL6, IL2,TNF-α, IL17)

•Multiple Sclerosis (IL12, INF, TNF-α)

•Diabetys type I (IL1, TNF-α, INF-γ, IL17)

•Tuberculosis (IL12, IL18)

• Autoimmune endocrine pathologies

•IBD (IL1, IL6, TNF-α, IL23, IL17)

•Allergy (IL4-IL5-IL13)

•Asthma (IL4-IL10)

•Atopic dermatitis (IL4-IL10)

•LES (IL10-IL6, IL17)

•Sclerodermia (IL17-IL6)

•HIV


Th1 Hypercativation

Diseases

Th2 Hypercativation

diseases




•…

Th1 Hypercativation

Diseases

Th2 Hypercativation

diseases

•Psoriasis (IL12, IL23)

•Crohn D. (IL12 IL6, TNF-α, IL18)

•Alopecia (IL1, TNF-alfa, IL8)



Trial Design Issues

• Choice of an appropriate methodology• Internal and external validity• Even qualitative changes can be

subjected to validated methods of quantification


Trial Design Issues

• Clinical outcome measures must reflect the ‘whole person’ approach

• Quality of Life assessment is as important as physical health determinants.

• Qualitative studies followed by pilot studies and RCT.


Summary

• We have explored a new frontier in terms of the use of PNEI and biological molecules

• New techniques are becoming available to study a possible mechanism of action

• Further research is needed, trial design must have rigor and reflect CAM aims


Contact DetailsClaire Haresnape

Bed (Hons)Research Student

Registered Homotoxicologist

�Charterhouse Square

London, EC1M 6BQ, [email protected]

0772 006 0116

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