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PHYSIOLOGICAL REGULATING MEDICINE 1/2007
INFLAMMATION AND
PHYSIOLOGICAL REGULATING
MEDICINE
– NEW IDEAS AND INNOVATIVE MEDICAL
PRODUCTS
Cytokines (CKs) are proteins secreted by cells
of both the innate Immune System (true mobi-
le Nervous System) and the acquired Immune
System in response to antigens that induce va-
rious responses according to the cell types in-
volved in the mechanisms of stress-immunity-
inflammation.
Due to their peculiarities as biological motors-
messengers-modifiers-modulators - oriented
toward coherent (homeostatic-homeodynamic)
equilibrium - and consequently to preservation
of the individual - CKs appear in the early sta-
ges of the history of life: the Epstein-Barr vi-
rus contains a homologous gene to IL-10; the
transduction mechanism of IL-1 is Toll type,
from the name of the same transduction me-
chanism discovered in Drosophila. The evolu-
tion of the species is nothing more than the
evolution of the Immune System. CKs have a
direct general mechanism of action on activa-
tion (differentiation + lymphocyte growth) and
implementation (elimination of the stressor).
CKs secretion is: 1) a brief and self-limiting
event; 2) pleiotropic, redundant, synergic, an-
tagonist. CKs influence the synthesis and ac-
tion of other CKs (immune cascade confirmed
by natural selection as the hormonal, coagu-
lation, and nervous cascade) requiring specific
target receptors boosted by external signals
to the target cells, which react by modifying ge-
ne expression (start-up of silent genes).
- A complete and effective targeted biological
response is achieved with the occupation of a
minimal quantity of receptors (e.g. no more
than 1% - 2% for IL-1) and with characteristi-
cally low-dose and low titred physiological di-
lutions all below Avogadro's Number. Molecu-
lar intelligence, coherence domains and elec-
tromagnetic superdomains are topics verified
and accepted by the international scientific
community. Together with the physiological di-
lutions (the same that operate in living orga-
nisms) they are administered with dedicated
and innovative medical products characteristic
of Physiological Regulating Medicine. They re-
present a major advance in homeopathy and
homotoxicology, by endorsing them as an ad-
vanced objective in progress workshops for fu-
ture developments of low-dose sciences.
- Immune Physiological Regulating Medicine -
resetting, promotion and coordination of the al-
tered immune language - includes the use of
PRM complex remedies.
In particular, the characteristics of Guna®
-Arth-
ro drops, Guna®
-Flam drops and Guna injecta-
ble ampoules for pain therapy are highlighted.
INFLAMMATION,
CYTOKINES, HOMEOPATHISED CYTOKINES,
PHYSIOLOGICAL REGULATING MEDICINE
SUMMARY
L. Milani
CLINICAL
19
KEY WORDS
INTRODUCTION
Inflammation is useful to the body as it
is aimed at the limitation, destruction
and elimination of etiologic agents or
cellular detritus produced following tis-
sue damage. The final effect is the re-
storation of the pre-existing state prior
to the stressor with repair of the dama-
ge. Peripheral memory traces of the
event remain at the dendritic level, at
the central level and in the macropha-
ges in the form of an electromagnetic
template.
- Inflammation is an essential defensi-
ve phenomenon whose development
and conditions are articulated by mo-
lecular events programmed according
to an encoded procedure through me-
chanisms of convergent evolution: 1)
the Epstein-Barr virus contains a homo-
logous gene to that of human IL-10 that
encodes a product with similar activity
to that of the natural cytokine. This ma-
kes it possible to see that the acquisition
by the virus of the IL-10 gene during
evolution has conferred on the virus the
capacity to inhibit the immune respon-
se of the host and, consequently, a se-
lective benefit for its own survival; 2) the
IL-1 transduction mechanism is Toll
type, named after the one found in Dro-
sophila melanogaster, the fruit fly;
3) IL-1 α and IL-1 ß share the same rib-
bon-like structure folded at 12 points li-
ke the growth bonds of heparin and the
Kunitz-type inhibitors of trypsin; 4) re-
ceptor similarity of a number of che-
mokines with the Duffy AG that media-
tes the penetration of Plasmodium vivax
into erythrocytes. These examples of
"molecular archaeology" demonstrate
how the phylogenetic continuum is ac-
complished through progressive, im-
perceptible transformations of the ar-
chaic genomes, but only for the essen-
tial functions - among them molecular
defense and protection - the base-mo-
del (pattern) has remained essentially
unchanged in comparison to the one
that was active millions of years ago.
This type of “immune reductionism” ne-
vertheless had to be put to the test, not
only by external transformations, but al-
so in man by transformations induced
by his “reading” of the world, by the in-
terpretation of phenomena, logical and
analogical abilities, the awareness of in-
tellectual superiority in comparison to
other animal creatures, the sensation of
being different and conscious, the un-
conscious feeling of carrying an effi-
cient and effective frontal neocortex.
- Tissue stress (infection, nonself, exo-
/endogenous toxicosis) of the inferior
Phyla turns into somatic stress involving
complex apparatuses and systems in
20
PHYSIOLOGICAL REGULATING MEDICINE 1/2007
fish, reptiles and birds leaving the field
open to the emotional stress specific to
mammals that turns into a typical
psychic and spiritual stress - real be-
cause it is at the highest point of the
evolutionary pyramid - in man.
The alerting of the non-specific and spe-
cific, local and systemic Immune
System (I.S.) through neuro-endocrine
mediation creates the basis for the sur-
vival of the individual and the species,
the condicio sine qua non for shaping -
by adapting it -the appropriate indivi-
dual response to internal and external
requirements (TAB. 1). The relationships
between the human Nervous System
and I.S. are numerous (Milani, 2006):
- Structural polyphormism
- Immaturity at birth
- Short- and long-term memory
- Amplification mechanisms of the
afferent stimuli
- Control of the stressors in excess
- Auto-inhibition
- Local and remote effects
- Various stereotyped responses.
The I.S. can be interpreted as a true mo-
bile Nervous System.
The junction where stress, immunity
and pain are sorted is represented by the
limbic brain which influences reactive
behaviour with the memory-affective-
emotional dimension (TAB. 2).
® Thus, the same, with an almost iden-
tical genome; but different, therefore,
due to the individuality of the cultural
and emotional experience.
Purposes that are, so to speak, “histori-
cal”, “phyletic”, almost mechanically
Synoptic table
illustrating the
different bonds,
correlations and
influences that the
single elements of
the P.N.E.I develop
in response to a
stressor in the
genesis of
inflammation.
Below: role of
Physiological
Regulating
Medicine that
unifies selected
concepts from
Homeopathy,
Homotoxicology and
basic and applied
scientific research,
promoting an
innovative,
preventive and
therapeutic method,
responding to the
needs of modern
biological medicine.
TAB. 1
21
PHYSIOLOGICAL REGULATING MEDICINE 1/2007
predetermined emerge in the N.E.I. re-
sponses of every individual into a com-
mon file; but it is really the P. the
acronym header that informs the subse-
quent N.E.I cascade by making each
one - in the biological sense - unique
and unrepeatable. This difference is
greatly valued by Physiological Regula-
ting Medicine: a standardized medical
therapy must always be integrated from
individualized therapeutic approaches,
which are varying, dynamic and dedi-
cated in accordance with the evolution
of the clinical condition. In such a con-
text, the concept of homeopathic simil-
limum fits perfectly with this statement,
demonstrating its puzzling modernity.
CYTOKINES AND
INFLAMMATION
Cytokines (CKs) are peptides produced
by different lines of cells of both the in-
nate and specific I.S. in response to a
wide variety of inducing stimuli, mainly
germs and antigens that produce va-
rious responses depending on the cell
types involved in inflammation and im-
munity. In some ways, they are similar
to the peptide hormones though these
are secreted by specific endocrine
structures: they partially share the cha-
racteristic of highly informative mole-
cules on target cells and tissues due to
their telecrine function, acting on tar-
gets at a site different to the one in
which they were produced (the CKs au-
tocrine action on the cell that has se-
creted it and paracrine action on va-
rious neighbouring cells are specific to
the CKs). This is a para-endocrine func-
tion as it is transported by the blood in
order to interact with the cells that ha-
ve the receptors they can bind with.
The functional characteristics of the
CKs are illustrated schematically, but in
essence, in TAB. 3. The second function
combines 4 effects: pleiotropism, the
capacity to affect more target cells, as
in the case of IL-4 (the response to the
stimulation varies according to the
cytotype with which they have reacted
through specific high-affinity receptors
expressed on the surface of the target
cells); antagonism as with IFN ␥ acti-
vating and IL-4 inhibiting macrophage
function; redundancy as with IL-2, IL-
4, IL-5 which induce the proliferation
of B lymphocytes; synergy as with IFN
␥ and TNF ␣ by activating the major hi-
stocompatibility complex (MHC) on
many cell types. An effect not suffi-
ciently exploited is the synergy of ac-
tion of the CKs (explosion of effects) in
sequence (cascade of CKs). One hour
after the inoculation of LPS (endotoxin
from Gram- bacteria) a peak TNF ␣
concentration is obtained experimen-
tally. While the TNF ␣ activity is beco-
ming exhausted, the activity of IL-1 is
boosted; as this declines, the activity of
IL-12 increases. The three CKs are se-
creted only by macrophages and NK
cells. The whole proinflammatory phe-
nomenon lasts 6 hours on average, en-
suring that a suitable status is maintai-
ned. The organic response is thereby
optimized by a steady, secure and ef-
fective plateau so that the host can ade-
TAB. 2
A stressor of
similar intensity
and duration
produces different
(sometimes
opposing) effects in
individuals differing
by the peculiarity of
the biological
unicum expressed
by each person.
To this is added a
common basic
stereotyped
response not
depending on
individual need but
on the behaviour of
the species.
22
PHYSIOLOGICAL REGULATING MEDICINE 1/2007
quately neutralize the cytolytic effect of
the LPS. Individually, none of the three
CKs is able to neutralize the LPS, even
in greater than physiological concen-
trations. On the contrary, they trigger
receptor down-regulation with inhibi-
tion of the specific goals.
Physiologically, CKs are not stored in
the cells; their synthesis requires the
transcription of genes that have been si-
lent until now and are activated after
stimulation of the cell. Such transcrip-
tion activation is transitory. The RNAm
that encode the CKs are unstable. Con-
sequently, the secretion of cytokines is
brief and self-limiting so the interven-
tion of more CKs “in relay” is necessary
to support a biologically targeted effect
(telenomy of the natural phenomena).
These 4 effects are responsible for the
Siedeck ternary rhythm: after a first
phase of activation in which lymphocy-
te differentiation and growth occur
(Phase A of Hoff's vegetative commu-
tation - proinflammation = Selye's
shock phase) follows the implementa-
tion phase through the attempt to eli-
minate the stressor (anti-inflammatory
Phase B of Hoff's vegetative commuta-
tion = Selye's counter-shock phase).
Acute inflammation includes three ma-
jor phenomena: 1) vascular alterations
- neurogenic inflammation (initial va-
soconstriction, active hyperemia, pas-
sive hyperemia and stasis) which invol-
ve the caliber and blood flow in arte-
rioles, venules and capillaries; 2) for-
mation of exudate; 3) migration of leu-
cocytes in the extracellular matrix
(ECM).The vasoconstriction induced by
adrenaline and the subsequent vasodi-
latation in which histamine, serotonin
and prostaglandins E2 and G2 are in-
volved, are equivalent to Selye's fight
phase. The allopathic use of antihista-
mines and COX-2 inhibitors (cyclooxy-
genase - lipoxygenase) inhibits the va-
sodilatation by stopping passive hype-
remia, diapedesis, formation of exuda-
te and phagocytosis, with a resulting
stand-by state and toxicosis of the ECM
due to the accumulation of antigen de-
tritus. The prolonged use of these drugs
may result in chronic and autoimmu-
ne pathologies. The angioinflammation
turns into histoinflammation.
- The Biological Division in the Recke-
weg Six Phases Table is nothing more
than the watershed between angio- and
histoinflammation. The sudden inter-
ruption of the phenomena following on
Phase A can indicate temporary aboli-
tion of the symptoms, resetting the
physiological course that is articulated
by a strict and predetermined timeta-
ble: a tissue that is not completely hea-
led (end of Phase B) represents - even
after years - a tissue of less resistance,
serious irritation for the CNS, a prodro-
me for various diseases, even involving
organs derived from different embryo-
nic germ layers from those from which
the organ originates that is the site of
the earlier pathology. In actual fact, the
recovery process is achieved when a
balance is established between Th1
andTh2 immunity regulated by Th3 im-
munity, immune tolerance - memory
that fights the plus-inflammation and
that becomes established as a result of
a functional deficit of the Th3 system.
- Terms such as “relapse”, “slow and
difficult recovery”, “chronification”,
“progressive vicariation” are different
expressions highlighting a single con-
cept: non-physiological recovery.
No therapy is really effective if it does
not respect the clock that million of
years have standardized.
KEY-LOCK - STEREOSCOPIC
COMPLEMENTARITY
CKs receptors are transmembrane pro-
tein structures with an external part and
an internal part that triggers the casca-
de of signals (transduction).
Two molecules are attracted only if they
resonate at the same frequency of oscil-
lation. CKs receptors are divisible into 5
families in accordance with their three-
dimensional morphology; each of them
induces a different mode of transduc-
TAB. 3
The “motors”
of the CKs.
23
PHYSIOLOGICAL REGULATING MEDICINE 1/2007
tion (TAB. 4). Several receptors are co-
upled to others control the amount of
information: an interesting analogy is
with the inhibitory corticospinal ner-
vous tract blocking an excess of peri-
pheral information, a type of protective
relay that interrupts the circuit so as not
to damage the apparatus.
A paradigmatic example is provided by
IL-1 R2 (IL-1 Ra, IL-1 ra), present only
on the B lymphocytes, which does not
translate any activation signal; it is a real
molecular trap, a decoy or false recep-
tor that blocks the excess IL-1 in order
to limit and circumscribe the inflam-
mation and prevent the B lymphocyte
from immediately producing IgGs, thus
allowing the inflammation to become
activated. This inhibitory receptor,
which is competitive-antagonist of the
real IL-1 receptor (IL-1R1) seems to ha-
ve evolved before the division of IL-1 in-
to the two subclasses IL-1 ␣ and IL-1 ␤.
- Anakinra, a recombinant IL-R2, eta-
nercept and infliximab which block the
TNF ␣ receptors have recently been in-
troduced in the conventional therapy of
rheumatoid arthritis.
These drugs have opened up interesting
therapeutic perspectives although the
negative side effects are particularly im-
pressive. For anakinra: pain, bruises,
bleeding at the injection site, which fre-
quently force the patients to discontinue
treatment (Cohen, 2002).
Other adverse reactions are headache
and abdominal pain (Cohen, 2002). For
etanercept and infliximab: neutropenia,
increased incidence of serious infec-
tions.
The receptors bind the CKs with high
affinity and a constant dissociation of
10-10
-10-12
M.
Consequently, to make a receptor per-
form its function, very low cytokine
concentrations are sufficient because
the number of receptors per cell is re-
latively low (≈ from 100 to 1000). Besi-
des the intrinsic characteristics, the con-
centrations of CKs are very important for
therapeutic purposes as different con-
centrations induce different effects.
For example, low plasma concentra-
tions of TNF and IL-1 (10-9
M) induce:
1) leucocyte activation, 2) secretion of
IL-1, chemokines and adhesion mole-
cules [local proinflammatory effects]; in
moderate concentration: 1) fever (hypo-
thalamic centre for temperature regula-
tion); 2) acute-phase proteins (liver); 3)
production of leucocytes (bone mar-
row); at plasma concentrations (≥ 10-7
M): septic shock with hypoglycaemia,
low endothelial resistance and forma-
tion of thrombosis, low cardiac output.
The similarities between the actions of
TNF and IL-1 depend on the common
transduction of the signal using similar
proteins, though they are structurally
different. The effect of the different con-
centrations of a biological active prin-
ciple had already been experimentally
highlighted (Pennec and Aubin, 1984):
10-5
M aconitine causes heart fibrilla-
tion; 10-7
M bradycardia; 10-18
M has no
effect on a healthy heart and there is a
normalization of the rhythm in the
preintoxicated, isolated and infused eel
heart (Anguilla anguilla Linn.). In a re-
cent micro-auto radiographic receptor
study (Stumpf, 2005) it was shown that
low-dose and low-titred substances in-
teract with the cell nucleus, while hi-
gher concentrations trigger a cellular re-
sponse at cytoplasmic level.
Chronologically, the effects of low-dose
immuno-modulants have been reported
by Poitevin et al. (1983), Wagner et al.
(1986), Poitevin et al. (1986), Wagner et
TAB. 4
The five family
types of CKs
receptors.
Some salient
characteristics
of the receptor of
the CKs are shown.
24
PHYSIOLOGICAL REGULATING MEDICINE 1/2007
al. (1988), Davenas et al. (1988), Poite-
vin et al. (1988), Daurat (1988), Enbergs
and Arndt (1993), Enbergs (1998), Belon
et al. (2004), Jäggi et al. (2005), Amadori
et al. (2007).
-There is no receptor turnover since the
receptor synthesis is regulated by ap-
propriate external signals to the cell:
the ligand CK and the specific receptor
are neosynthesised only if required and
simply do not exist when they are not
needed, complying closely with the na-
tural principle of parsimony.
CONTROL OF INFLAMMATION -
FROM PHYSIOLOGY TO THERAPY
-HOMEOPATHISED CYTOKINES
The control and the specific sequence
of the activator or suppressor stages of
the immune response are mediated by
cells through the release of proinflam-
matory and anti-inflammatory CKs:
- Th1 or proinflammatory: TNF ␣, IL-1
␣, IL-1 ␤, IL-2, IL-6, etc. (accepted to-
day: 13),
- Th2 or anti-inflammatory: IL-4, IL-10,
etc. (accepted today: 4).
The classic proinflammatory CK and the
first to be discovered is IL-1 (␣ and ␤ va-
riants). Once bound to the membrane
receptor - the ␣ barrel (12-stranded be-
ta-sheet structure) so-called from the
distinctive form of overlapped circles
spaced out by linear structures, a re-
ceptor shared with the M-CSF-Mono-
nuclear phagocyte colony stimulating
factor, of the cells of the endothelium,
epithelial keratinocytes, platelets, neu-
trophils and microglia, it enters the cyto-
plasm and binds to the NF-kb transcrip-
tion factor: this complex stimulates se-
veral signal molecules which can relea-
se several silent genes at nuclear level
allowing them to encode proinflamma-
tory proteins operating at the level of the
surrounding tissues.
The message also reaches the CNS by
inducing fever (endogenous pyrogen)
and alerting of the system (TAB. 5).
All the main functions of IL-1 ␣ and ␤
are illustrated synoptically in TAB. 6.
- On the whole, IL-1 (␣; ␤) activates type
2 cyclooxygenase (COX2) (effect 1),
prostaglandin E2 (effect 2), nitric oxide
(effect 3), activating and accelerating
the inflammatory process.
® Consequently, the Anti IL-1 (Anti IL-
1 ␣, Anti IL-1 ␤) inhibits effect 1 (like the
NSAIDs), effect 2 (like the corticoste-
roids) and effect 3 (like the salicylates),
without the negative side effects indu-
ced by these synthetic drugs.
The homeopathised Anti IL-1 ␣ and ␤
are therefore used successfully in the
therapy of the osteo-arthro-myofascial
pain (inflammation of joints and myofa-
scial structures) as according to the con-
cepts specific to Physiological Regula-
ting Medicine (PRM).
PRM IN INFLAMMATION AND
PAIN CONTROL
Patients suffering from painful and in-
flammatory diseases of orthopaedic,
rheumatologic and traumatologic natu-
re account for 25-35% of all patients
consulting a general practitioner.
A great resource for a general practitioner
is to be able to use effective medical pro-
ducts acting rapidly and with no negative
TAB. 5
Synoptic table
illustrating how
IL-1␣ and ␤ bind
to the IL-1 R1
receptor.
-This is the prime
mover of the
coding of proteins
and inflammatory
peptides.
25
PHYSIOLOGICAL REGULATING MEDICINE 1/2007
nor recurrent side effects. PRM is based
on a wide range of medical products ha-
ving all the above characteristics besides
being innovative in some respects.
̈ GUNA®
-ARTHRO drops
GUNA®
-ARTHRO is a PRM product
composed of 5 therapeutical cores:
Anti-inflammatory, Antidegenerative,
TAB. 6 Activity, phenomena, epiphenomena and proinflammatory effects of IL-1αα and ββ.
Metabolic, Trophic and PNEI core.
- Uses: Osteoarticular degenerative pro-
cess of small joints (e.g.: in combination
with Guna®
-Polyarthritis + Guna®
-
HandFoot) and large joints (e.g.: in co-
xarthrosis or gonarthrosis in combina-
tion with Guna®
-Hip + Guna®
-Muscle),
inflammatory disease of the joints (in as-
sociation with Guna®
-Flam), osteoporo-
sis (in association with Osteobios®
).
̈ GUNA®
-FLAM drops
GUNA®
-FLAM is a PRM product com-
posed of 4 therapeutic cores: Antiseptic,
Antalgic, Neuro-endocrine and Anti-in-
flammatory core.
The Anti-inflammatory core includes
1 nosode (Pyrogenium), 4 single reme-
26
PHYSIOLOGICAL REGULATING MEDICINE 1/2007
dies of plant origin (Aconitum, Bella-
donna, Bryonia, Phytolacca), 3 single re-
medies of mineral origin (Ferrum
phosph., Hepar sulph. calc., Copper
gluconate), 2 metabolites of Krebs cycle
(Natrium pyr., Citricum ac.), 1 single re-
medy of animal origin (Apis) and 4 spe-
cific PRM remedies (Anti IL-1α 4C,TGF
1β 4C, IL-10 4C, Melatonin 4C).
- Uses: acute and chronic inflamma-
tions, pain of inflammatory origin.
̈ GUNA INJECTABLE AMPOULES
FOR PAIN THERAPY
The 10 Guna injectable ampoules for
Pain Management are specific and se-
lective for osteo-arthro-myofascial pain
and pathologies of every single soma-
tic anatomic part: Guna®
-Neck, Guna®
-
Thoracic, Guna®
-Lumbar, Guna®
-Shoul-
der (shoulder and elbow), Guna®
-Hip
(hip and knee), Guna®
-HandFoot, Gu-
na®
-Ischial, Guna®
-Polyarthritis, Guna®
-
Muscle and Guna®
-Neural.
Nine out of 10 contain Beta Endorphin
4C; 8 out of 10 contain Anti IL-1α 4C
and Anti IL-1β 4C, having a great pain-
killing and anti-inflammatory effect.
The homeopathic physiological micro-
doses involve no negative side-effects,
and help avoid any trouble concerning
tolerance as well as pharmacological
catabolite overload in ECM and organs.
̈ Guna®
-Arthro, Guna®
-Flam and the
10 Guna injectable ampoules for Pain
Management may be used in combi-
nation in an outpatient or home treat-
ment according to the needs of every
single clinical case.
CONCLUSIONS
For more than 150 years, due to the in-
trinsic characteristic of symptomatic
medicine, even with the integration of
new pathogenesis, classic Homeopathy
has remained closely and structurally
anchored to its historical roots (Milani,
2007).
Medicine of symptoms, if not adequa-
tely integrated with the new advance-
ment of the low dose - low titred ho-
meopathic immunobiotherapy, is desti-
ned to disappear: it does not have a
chance of progressing.
By means of an ambitious project,
Physiological Regulating Medicine (PRM)
has fully achieved the theoretical propo-
sals of Prof. H. Wagner.
In the 3rd
Italian National Congress of Ho-
meopathy: “Physics, biology, medicine.A
unifying approach” organized by A.I.O.T
(Italian Medical Association of Homoto-
xicology) in 1988, he pointed out (I quo-
te) the “characteristics of the immuno-
therapies to achieve the strengthening of
the non-specific defenses” which must
have:
1) Normative or modulating property
2) Similarity with the "biological
response modifiers"
3) Results achieved through
microdoses
4) Therapeutic results depending on:
a) dosage
b) administration type
c) administration time
d) immune status.
̈ Moreover, PRM does not use units that
have “similarity with the modifiers of the
biological response” [point 2)].
It uses the real modifiers of the biologi-
cal response - those that work physiolo-
gically at those concentrations!
- The rational inclusion in therapeutic
practice of homeopathised CKs, hor-
mones, neurotransmitters and homeo-
pathised peptides at the same dilution
in which they are physiologically pre-
sent and active in the human body and
the formulation of innovative medical
products containing unitaries of which
we know the active principles and their
action in the healthy and sick person,
define and are inherent to PRM, which
does not deny the past but faces the fu-
ture strong in the consciousness that it
can always be updated and adapt to the
new ideas and new solutions that scien-
ce will provide. I
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10) Milani L. - I tre cerebrotipi umani: riflessioni sul-
la loro funzione neurobiologica. La Med. Biol.;
1994/3, 35-41.
11) Milani L. - Dal fegato vaticinatore alla Nuova
Tavola delle Omotossicosi. Dai Punti di Weihe al
same-same-but-different nella terapia della
steatoepatite non alcoolica. La Med. Biol.;
2006/4, 13-26.
12) Milani L., Buttignol M. - Sulla purezza de “Ma-
teria Medica Pura” di Samuel Hahnemann. La
Med. Biol.; 2007/2, 47-55.
13) Pennec J.P., Aubin M. - Effect of Aconitum and
Veratrum on the isolated perfused heart of com-
mon eel (Anguilla anguilla). Comp. Biochem.
Physiol, 1984, 776:367-69.
14) Poitevin B. et Al. - The effects of Belladonna and
Ferrum phosphoricum on the chemulumine-
scence of human poly-morphonuclear neutro-
phils. Ann. Homéop. Fr.; 1983, 3: 5-12.
(translated title from French)
15) Poitevin B. et Al. - Approccio all'analisi quanti-
tativa dell'effetto di Apis mellifica sulla degranu-
lazione dei basofili umani coltivati in vitro. Innov.
Tech. Biol. Med.; 1986, 7: 64-68.
(translated title from French)
16) Poitevin B. et Al. - In vitro immunological degra-
nulation of human basophils is modulated by
lung histamine and Apis mellifica. Brit. J. Clin.
Pharmacol.; 1988, 25: 439-444.
17) Stumpf W.E. - J. Pharmacol. Toxicol. Methods;
2005. 51, (1), 25.
18) Wagner H. et Al. - Actions of homeophatic pre-
parations on fagocyte activity of granulocytes. In
vitro tests and double blind controlled studies.
Arzneim. Forsch./Drug Res.; 1986, 36: 1424-
1425. (translated title from German)
27
PHYSIOLOGICAL REGULATING MEDICINE 1/2007
19) Wagner H. - Studi immunologici in vitro e in vi-
vo con farmaci vegetali a bassi dosaggi. Rivista
Italiana di Omotossicologica; 1988/3, 13-19.
20) Wagner H. et Al. - Stimolazione in vitro dei lin-
fociti e dei granulociti umani mediante quantità
espresse in picogrammi e femtogrammi di agen-
ti citostatici. Arzneim. Forsch./Drug Res.; 1988,
38: 273-275. (translated title from German)
In addition, the following were consulted:
1) Abbas K., Lichtman A.H., Pober J.S. - Cellular
and molecular immunology. Saundres Com-
pany, Philadelphia; 2000.
2) Bharat B. et Al. - Human cytokines handbook for
basic and clinical research. Aggarwal. Jordan u.
Guttermann; 1996.
3) Dinarello C.A. - Biological basis for interleukin-
1 in disease. Blood; 87: 2095-2147; 1996.
4) Luster A.D. - Chemokines-chemotactic molecu-
les that mediate inflammation. New England
Journal of Medicine. 338: 436-445; 1998.
5) Milani L. - Homeomesotherapy for pain mana-
gement in primary chronic coxarthrosis with a
homeopathic injectable formulation. Physiologi-
cal Regulating Medicine, 2006/1; 9-18.
® Tables 1, 2, 5, 6 are original by the Author;
Tables 3, 4, are adapted explanations by the
Author in relation to the updated bibliography.
Author's address
Prof. Leonello Milani, MD, PhD
- Vice President of A.I.O.T.
- Scientific director of
“La Medicina Biologica”
and “Physiological Regulating
Medicine”
- Professor h.c. of the Higher
Institute of Health Studies,
Rome; a collaborative Centre
for the WHO
- Lecturer and tutor in the School
of Homeopathy, Homotoxicology
and Integrated Disciplines
-Academy of Biological
Medicine.
Via Vanvitelli 6
I - 20129 Milano

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PHYSIOLOGICAL REGULATING MEDICINE RESETS IMMUNE LANGUAGE

  • 1. PHYSIOLOGICAL REGULATING MEDICINE 1/2007 INFLAMMATION AND PHYSIOLOGICAL REGULATING MEDICINE – NEW IDEAS AND INNOVATIVE MEDICAL PRODUCTS Cytokines (CKs) are proteins secreted by cells of both the innate Immune System (true mobi- le Nervous System) and the acquired Immune System in response to antigens that induce va- rious responses according to the cell types in- volved in the mechanisms of stress-immunity- inflammation. Due to their peculiarities as biological motors- messengers-modifiers-modulators - oriented toward coherent (homeostatic-homeodynamic) equilibrium - and consequently to preservation of the individual - CKs appear in the early sta- ges of the history of life: the Epstein-Barr vi- rus contains a homologous gene to IL-10; the transduction mechanism of IL-1 is Toll type, from the name of the same transduction me- chanism discovered in Drosophila. The evolu- tion of the species is nothing more than the evolution of the Immune System. CKs have a direct general mechanism of action on activa- tion (differentiation + lymphocyte growth) and implementation (elimination of the stressor). CKs secretion is: 1) a brief and self-limiting event; 2) pleiotropic, redundant, synergic, an- tagonist. CKs influence the synthesis and ac- tion of other CKs (immune cascade confirmed by natural selection as the hormonal, coagu- lation, and nervous cascade) requiring specific target receptors boosted by external signals to the target cells, which react by modifying ge- ne expression (start-up of silent genes). - A complete and effective targeted biological response is achieved with the occupation of a minimal quantity of receptors (e.g. no more than 1% - 2% for IL-1) and with characteristi- cally low-dose and low titred physiological di- lutions all below Avogadro's Number. Molecu- lar intelligence, coherence domains and elec- tromagnetic superdomains are topics verified and accepted by the international scientific community. Together with the physiological di- lutions (the same that operate in living orga- nisms) they are administered with dedicated and innovative medical products characteristic of Physiological Regulating Medicine. They re- present a major advance in homeopathy and homotoxicology, by endorsing them as an ad- vanced objective in progress workshops for fu- ture developments of low-dose sciences. - Immune Physiological Regulating Medicine - resetting, promotion and coordination of the al- tered immune language - includes the use of PRM complex remedies. In particular, the characteristics of Guna® -Arth- ro drops, Guna® -Flam drops and Guna injecta- ble ampoules for pain therapy are highlighted. INFLAMMATION, CYTOKINES, HOMEOPATHISED CYTOKINES, PHYSIOLOGICAL REGULATING MEDICINE SUMMARY L. Milani CLINICAL 19 KEY WORDS INTRODUCTION Inflammation is useful to the body as it is aimed at the limitation, destruction and elimination of etiologic agents or cellular detritus produced following tis- sue damage. The final effect is the re- storation of the pre-existing state prior to the stressor with repair of the dama- ge. Peripheral memory traces of the event remain at the dendritic level, at the central level and in the macropha- ges in the form of an electromagnetic template. - Inflammation is an essential defensi- ve phenomenon whose development and conditions are articulated by mo- lecular events programmed according to an encoded procedure through me- chanisms of convergent evolution: 1) the Epstein-Barr virus contains a homo- logous gene to that of human IL-10 that encodes a product with similar activity to that of the natural cytokine. This ma- kes it possible to see that the acquisition by the virus of the IL-10 gene during evolution has conferred on the virus the capacity to inhibit the immune respon- se of the host and, consequently, a se- lective benefit for its own survival; 2) the IL-1 transduction mechanism is Toll type, named after the one found in Dro- sophila melanogaster, the fruit fly; 3) IL-1 α and IL-1 ß share the same rib- bon-like structure folded at 12 points li- ke the growth bonds of heparin and the Kunitz-type inhibitors of trypsin; 4) re- ceptor similarity of a number of che- mokines with the Duffy AG that media- tes the penetration of Plasmodium vivax into erythrocytes. These examples of "molecular archaeology" demonstrate how the phylogenetic continuum is ac- complished through progressive, im- perceptible transformations of the ar- chaic genomes, but only for the essen- tial functions - among them molecular defense and protection - the base-mo- del (pattern) has remained essentially unchanged in comparison to the one that was active millions of years ago. This type of “immune reductionism” ne- vertheless had to be put to the test, not only by external transformations, but al- so in man by transformations induced by his “reading” of the world, by the in- terpretation of phenomena, logical and analogical abilities, the awareness of in- tellectual superiority in comparison to other animal creatures, the sensation of being different and conscious, the un- conscious feeling of carrying an effi- cient and effective frontal neocortex. - Tissue stress (infection, nonself, exo- /endogenous toxicosis) of the inferior Phyla turns into somatic stress involving complex apparatuses and systems in
  • 2. 20 PHYSIOLOGICAL REGULATING MEDICINE 1/2007 fish, reptiles and birds leaving the field open to the emotional stress specific to mammals that turns into a typical psychic and spiritual stress - real be- cause it is at the highest point of the evolutionary pyramid - in man. The alerting of the non-specific and spe- cific, local and systemic Immune System (I.S.) through neuro-endocrine mediation creates the basis for the sur- vival of the individual and the species, the condicio sine qua non for shaping - by adapting it -the appropriate indivi- dual response to internal and external requirements (TAB. 1). The relationships between the human Nervous System and I.S. are numerous (Milani, 2006): - Structural polyphormism - Immaturity at birth - Short- and long-term memory - Amplification mechanisms of the afferent stimuli - Control of the stressors in excess - Auto-inhibition - Local and remote effects - Various stereotyped responses. The I.S. can be interpreted as a true mo- bile Nervous System. The junction where stress, immunity and pain are sorted is represented by the limbic brain which influences reactive behaviour with the memory-affective- emotional dimension (TAB. 2). ® Thus, the same, with an almost iden- tical genome; but different, therefore, due to the individuality of the cultural and emotional experience. Purposes that are, so to speak, “histori- cal”, “phyletic”, almost mechanically Synoptic table illustrating the different bonds, correlations and influences that the single elements of the P.N.E.I develop in response to a stressor in the genesis of inflammation. Below: role of Physiological Regulating Medicine that unifies selected concepts from Homeopathy, Homotoxicology and basic and applied scientific research, promoting an innovative, preventive and therapeutic method, responding to the needs of modern biological medicine. TAB. 1
  • 3. 21 PHYSIOLOGICAL REGULATING MEDICINE 1/2007 predetermined emerge in the N.E.I. re- sponses of every individual into a com- mon file; but it is really the P. the acronym header that informs the subse- quent N.E.I cascade by making each one - in the biological sense - unique and unrepeatable. This difference is greatly valued by Physiological Regula- ting Medicine: a standardized medical therapy must always be integrated from individualized therapeutic approaches, which are varying, dynamic and dedi- cated in accordance with the evolution of the clinical condition. In such a con- text, the concept of homeopathic simil- limum fits perfectly with this statement, demonstrating its puzzling modernity. CYTOKINES AND INFLAMMATION Cytokines (CKs) are peptides produced by different lines of cells of both the in- nate and specific I.S. in response to a wide variety of inducing stimuli, mainly germs and antigens that produce va- rious responses depending on the cell types involved in inflammation and im- munity. In some ways, they are similar to the peptide hormones though these are secreted by specific endocrine structures: they partially share the cha- racteristic of highly informative mole- cules on target cells and tissues due to their telecrine function, acting on tar- gets at a site different to the one in which they were produced (the CKs au- tocrine action on the cell that has se- creted it and paracrine action on va- rious neighbouring cells are specific to the CKs). This is a para-endocrine func- tion as it is transported by the blood in order to interact with the cells that ha- ve the receptors they can bind with. The functional characteristics of the CKs are illustrated schematically, but in essence, in TAB. 3. The second function combines 4 effects: pleiotropism, the capacity to affect more target cells, as in the case of IL-4 (the response to the stimulation varies according to the cytotype with which they have reacted through specific high-affinity receptors expressed on the surface of the target cells); antagonism as with IFN ␥ acti- vating and IL-4 inhibiting macrophage function; redundancy as with IL-2, IL- 4, IL-5 which induce the proliferation of B lymphocytes; synergy as with IFN ␥ and TNF ␣ by activating the major hi- stocompatibility complex (MHC) on many cell types. An effect not suffi- ciently exploited is the synergy of ac- tion of the CKs (explosion of effects) in sequence (cascade of CKs). One hour after the inoculation of LPS (endotoxin from Gram- bacteria) a peak TNF ␣ concentration is obtained experimen- tally. While the TNF ␣ activity is beco- ming exhausted, the activity of IL-1 is boosted; as this declines, the activity of IL-12 increases. The three CKs are se- creted only by macrophages and NK cells. The whole proinflammatory phe- nomenon lasts 6 hours on average, en- suring that a suitable status is maintai- ned. The organic response is thereby optimized by a steady, secure and ef- fective plateau so that the host can ade- TAB. 2 A stressor of similar intensity and duration produces different (sometimes opposing) effects in individuals differing by the peculiarity of the biological unicum expressed by each person. To this is added a common basic stereotyped response not depending on individual need but on the behaviour of the species.
  • 4. 22 PHYSIOLOGICAL REGULATING MEDICINE 1/2007 quately neutralize the cytolytic effect of the LPS. Individually, none of the three CKs is able to neutralize the LPS, even in greater than physiological concen- trations. On the contrary, they trigger receptor down-regulation with inhibi- tion of the specific goals. Physiologically, CKs are not stored in the cells; their synthesis requires the transcription of genes that have been si- lent until now and are activated after stimulation of the cell. Such transcrip- tion activation is transitory. The RNAm that encode the CKs are unstable. Con- sequently, the secretion of cytokines is brief and self-limiting so the interven- tion of more CKs “in relay” is necessary to support a biologically targeted effect (telenomy of the natural phenomena). These 4 effects are responsible for the Siedeck ternary rhythm: after a first phase of activation in which lymphocy- te differentiation and growth occur (Phase A of Hoff's vegetative commu- tation - proinflammation = Selye's shock phase) follows the implementa- tion phase through the attempt to eli- minate the stressor (anti-inflammatory Phase B of Hoff's vegetative commuta- tion = Selye's counter-shock phase). Acute inflammation includes three ma- jor phenomena: 1) vascular alterations - neurogenic inflammation (initial va- soconstriction, active hyperemia, pas- sive hyperemia and stasis) which invol- ve the caliber and blood flow in arte- rioles, venules and capillaries; 2) for- mation of exudate; 3) migration of leu- cocytes in the extracellular matrix (ECM).The vasoconstriction induced by adrenaline and the subsequent vasodi- latation in which histamine, serotonin and prostaglandins E2 and G2 are in- volved, are equivalent to Selye's fight phase. The allopathic use of antihista- mines and COX-2 inhibitors (cyclooxy- genase - lipoxygenase) inhibits the va- sodilatation by stopping passive hype- remia, diapedesis, formation of exuda- te and phagocytosis, with a resulting stand-by state and toxicosis of the ECM due to the accumulation of antigen de- tritus. The prolonged use of these drugs may result in chronic and autoimmu- ne pathologies. The angioinflammation turns into histoinflammation. - The Biological Division in the Recke- weg Six Phases Table is nothing more than the watershed between angio- and histoinflammation. The sudden inter- ruption of the phenomena following on Phase A can indicate temporary aboli- tion of the symptoms, resetting the physiological course that is articulated by a strict and predetermined timeta- ble: a tissue that is not completely hea- led (end of Phase B) represents - even after years - a tissue of less resistance, serious irritation for the CNS, a prodro- me for various diseases, even involving organs derived from different embryo- nic germ layers from those from which the organ originates that is the site of the earlier pathology. In actual fact, the recovery process is achieved when a balance is established between Th1 andTh2 immunity regulated by Th3 im- munity, immune tolerance - memory that fights the plus-inflammation and that becomes established as a result of a functional deficit of the Th3 system. - Terms such as “relapse”, “slow and difficult recovery”, “chronification”, “progressive vicariation” are different expressions highlighting a single con- cept: non-physiological recovery. No therapy is really effective if it does not respect the clock that million of years have standardized. KEY-LOCK - STEREOSCOPIC COMPLEMENTARITY CKs receptors are transmembrane pro- tein structures with an external part and an internal part that triggers the casca- de of signals (transduction). Two molecules are attracted only if they resonate at the same frequency of oscil- lation. CKs receptors are divisible into 5 families in accordance with their three- dimensional morphology; each of them induces a different mode of transduc- TAB. 3 The “motors” of the CKs.
  • 5. 23 PHYSIOLOGICAL REGULATING MEDICINE 1/2007 tion (TAB. 4). Several receptors are co- upled to others control the amount of information: an interesting analogy is with the inhibitory corticospinal ner- vous tract blocking an excess of peri- pheral information, a type of protective relay that interrupts the circuit so as not to damage the apparatus. A paradigmatic example is provided by IL-1 R2 (IL-1 Ra, IL-1 ra), present only on the B lymphocytes, which does not translate any activation signal; it is a real molecular trap, a decoy or false recep- tor that blocks the excess IL-1 in order to limit and circumscribe the inflam- mation and prevent the B lymphocyte from immediately producing IgGs, thus allowing the inflammation to become activated. This inhibitory receptor, which is competitive-antagonist of the real IL-1 receptor (IL-1R1) seems to ha- ve evolved before the division of IL-1 in- to the two subclasses IL-1 ␣ and IL-1 ␤. - Anakinra, a recombinant IL-R2, eta- nercept and infliximab which block the TNF ␣ receptors have recently been in- troduced in the conventional therapy of rheumatoid arthritis. These drugs have opened up interesting therapeutic perspectives although the negative side effects are particularly im- pressive. For anakinra: pain, bruises, bleeding at the injection site, which fre- quently force the patients to discontinue treatment (Cohen, 2002). Other adverse reactions are headache and abdominal pain (Cohen, 2002). For etanercept and infliximab: neutropenia, increased incidence of serious infec- tions. The receptors bind the CKs with high affinity and a constant dissociation of 10-10 -10-12 M. Consequently, to make a receptor per- form its function, very low cytokine concentrations are sufficient because the number of receptors per cell is re- latively low (≈ from 100 to 1000). Besi- des the intrinsic characteristics, the con- centrations of CKs are very important for therapeutic purposes as different con- centrations induce different effects. For example, low plasma concentra- tions of TNF and IL-1 (10-9 M) induce: 1) leucocyte activation, 2) secretion of IL-1, chemokines and adhesion mole- cules [local proinflammatory effects]; in moderate concentration: 1) fever (hypo- thalamic centre for temperature regula- tion); 2) acute-phase proteins (liver); 3) production of leucocytes (bone mar- row); at plasma concentrations (≥ 10-7 M): septic shock with hypoglycaemia, low endothelial resistance and forma- tion of thrombosis, low cardiac output. The similarities between the actions of TNF and IL-1 depend on the common transduction of the signal using similar proteins, though they are structurally different. The effect of the different con- centrations of a biological active prin- ciple had already been experimentally highlighted (Pennec and Aubin, 1984): 10-5 M aconitine causes heart fibrilla- tion; 10-7 M bradycardia; 10-18 M has no effect on a healthy heart and there is a normalization of the rhythm in the preintoxicated, isolated and infused eel heart (Anguilla anguilla Linn.). In a re- cent micro-auto radiographic receptor study (Stumpf, 2005) it was shown that low-dose and low-titred substances in- teract with the cell nucleus, while hi- gher concentrations trigger a cellular re- sponse at cytoplasmic level. Chronologically, the effects of low-dose immuno-modulants have been reported by Poitevin et al. (1983), Wagner et al. (1986), Poitevin et al. (1986), Wagner et TAB. 4 The five family types of CKs receptors. Some salient characteristics of the receptor of the CKs are shown.
  • 6. 24 PHYSIOLOGICAL REGULATING MEDICINE 1/2007 al. (1988), Davenas et al. (1988), Poite- vin et al. (1988), Daurat (1988), Enbergs and Arndt (1993), Enbergs (1998), Belon et al. (2004), Jäggi et al. (2005), Amadori et al. (2007). -There is no receptor turnover since the receptor synthesis is regulated by ap- propriate external signals to the cell: the ligand CK and the specific receptor are neosynthesised only if required and simply do not exist when they are not needed, complying closely with the na- tural principle of parsimony. CONTROL OF INFLAMMATION - FROM PHYSIOLOGY TO THERAPY -HOMEOPATHISED CYTOKINES The control and the specific sequence of the activator or suppressor stages of the immune response are mediated by cells through the release of proinflam- matory and anti-inflammatory CKs: - Th1 or proinflammatory: TNF ␣, IL-1 ␣, IL-1 ␤, IL-2, IL-6, etc. (accepted to- day: 13), - Th2 or anti-inflammatory: IL-4, IL-10, etc. (accepted today: 4). The classic proinflammatory CK and the first to be discovered is IL-1 (␣ and ␤ va- riants). Once bound to the membrane receptor - the ␣ barrel (12-stranded be- ta-sheet structure) so-called from the distinctive form of overlapped circles spaced out by linear structures, a re- ceptor shared with the M-CSF-Mono- nuclear phagocyte colony stimulating factor, of the cells of the endothelium, epithelial keratinocytes, platelets, neu- trophils and microglia, it enters the cyto- plasm and binds to the NF-kb transcrip- tion factor: this complex stimulates se- veral signal molecules which can relea- se several silent genes at nuclear level allowing them to encode proinflamma- tory proteins operating at the level of the surrounding tissues. The message also reaches the CNS by inducing fever (endogenous pyrogen) and alerting of the system (TAB. 5). All the main functions of IL-1 ␣ and ␤ are illustrated synoptically in TAB. 6. - On the whole, IL-1 (␣; ␤) activates type 2 cyclooxygenase (COX2) (effect 1), prostaglandin E2 (effect 2), nitric oxide (effect 3), activating and accelerating the inflammatory process. ® Consequently, the Anti IL-1 (Anti IL- 1 ␣, Anti IL-1 ␤) inhibits effect 1 (like the NSAIDs), effect 2 (like the corticoste- roids) and effect 3 (like the salicylates), without the negative side effects indu- ced by these synthetic drugs. The homeopathised Anti IL-1 ␣ and ␤ are therefore used successfully in the therapy of the osteo-arthro-myofascial pain (inflammation of joints and myofa- scial structures) as according to the con- cepts specific to Physiological Regula- ting Medicine (PRM). PRM IN INFLAMMATION AND PAIN CONTROL Patients suffering from painful and in- flammatory diseases of orthopaedic, rheumatologic and traumatologic natu- re account for 25-35% of all patients consulting a general practitioner. A great resource for a general practitioner is to be able to use effective medical pro- ducts acting rapidly and with no negative TAB. 5 Synoptic table illustrating how IL-1␣ and ␤ bind to the IL-1 R1 receptor. -This is the prime mover of the coding of proteins and inflammatory peptides.
  • 7. 25 PHYSIOLOGICAL REGULATING MEDICINE 1/2007 nor recurrent side effects. PRM is based on a wide range of medical products ha- ving all the above characteristics besides being innovative in some respects. ̈ GUNA® -ARTHRO drops GUNA® -ARTHRO is a PRM product composed of 5 therapeutical cores: Anti-inflammatory, Antidegenerative, TAB. 6 Activity, phenomena, epiphenomena and proinflammatory effects of IL-1αα and ββ. Metabolic, Trophic and PNEI core. - Uses: Osteoarticular degenerative pro- cess of small joints (e.g.: in combination with Guna® -Polyarthritis + Guna® - HandFoot) and large joints (e.g.: in co- xarthrosis or gonarthrosis in combina- tion with Guna® -Hip + Guna® -Muscle), inflammatory disease of the joints (in as- sociation with Guna® -Flam), osteoporo- sis (in association with Osteobios® ). ̈ GUNA® -FLAM drops GUNA® -FLAM is a PRM product com- posed of 4 therapeutic cores: Antiseptic, Antalgic, Neuro-endocrine and Anti-in- flammatory core. The Anti-inflammatory core includes 1 nosode (Pyrogenium), 4 single reme-
  • 8. 26 PHYSIOLOGICAL REGULATING MEDICINE 1/2007 dies of plant origin (Aconitum, Bella- donna, Bryonia, Phytolacca), 3 single re- medies of mineral origin (Ferrum phosph., Hepar sulph. calc., Copper gluconate), 2 metabolites of Krebs cycle (Natrium pyr., Citricum ac.), 1 single re- medy of animal origin (Apis) and 4 spe- cific PRM remedies (Anti IL-1α 4C,TGF 1β 4C, IL-10 4C, Melatonin 4C). - Uses: acute and chronic inflamma- tions, pain of inflammatory origin. ̈ GUNA INJECTABLE AMPOULES FOR PAIN THERAPY The 10 Guna injectable ampoules for Pain Management are specific and se- lective for osteo-arthro-myofascial pain and pathologies of every single soma- tic anatomic part: Guna® -Neck, Guna® - Thoracic, Guna® -Lumbar, Guna® -Shoul- der (shoulder and elbow), Guna® -Hip (hip and knee), Guna® -HandFoot, Gu- na® -Ischial, Guna® -Polyarthritis, Guna® - Muscle and Guna® -Neural. Nine out of 10 contain Beta Endorphin 4C; 8 out of 10 contain Anti IL-1α 4C and Anti IL-1β 4C, having a great pain- killing and anti-inflammatory effect. The homeopathic physiological micro- doses involve no negative side-effects, and help avoid any trouble concerning tolerance as well as pharmacological catabolite overload in ECM and organs. ̈ Guna® -Arthro, Guna® -Flam and the 10 Guna injectable ampoules for Pain Management may be used in combi- nation in an outpatient or home treat- ment according to the needs of every single clinical case. CONCLUSIONS For more than 150 years, due to the in- trinsic characteristic of symptomatic medicine, even with the integration of new pathogenesis, classic Homeopathy has remained closely and structurally anchored to its historical roots (Milani, 2007). Medicine of symptoms, if not adequa- tely integrated with the new advance- ment of the low dose - low titred ho- meopathic immunobiotherapy, is desti- ned to disappear: it does not have a chance of progressing. By means of an ambitious project, Physiological Regulating Medicine (PRM) has fully achieved the theoretical propo- sals of Prof. H. Wagner. In the 3rd Italian National Congress of Ho- meopathy: “Physics, biology, medicine.A unifying approach” organized by A.I.O.T (Italian Medical Association of Homoto- xicology) in 1988, he pointed out (I quo- te) the “characteristics of the immuno- therapies to achieve the strengthening of the non-specific defenses” which must have: 1) Normative or modulating property 2) Similarity with the "biological response modifiers" 3) Results achieved through microdoses 4) Therapeutic results depending on: a) dosage b) administration type c) administration time d) immune status. ̈ Moreover, PRM does not use units that have “similarity with the modifiers of the biological response” [point 2)]. It uses the real modifiers of the biologi- cal response - those that work physiolo- gically at those concentrations! - The rational inclusion in therapeutic practice of homeopathised CKs, hor- mones, neurotransmitters and homeo- pathised peptides at the same dilution in which they are physiologically pre- sent and active in the human body and the formulation of innovative medical products containing unitaries of which we know the active principles and their action in the healthy and sick person, define and are inherent to PRM, which does not deny the past but faces the fu- ture strong in the consciousness that it can always be updated and adapt to the new ideas and new solutions that scien- ce will provide. I References 1) Amadori M. et Al. - Anti-inflammatory activity of low dose IFN-α. In vitro study on porcine leu- kocytes. Physiological Regulating Medicine, 2007/1; 29-35. 2) Belon P. et Al. - Histamine dilutions modulate ba- sophil activation. Inflamm Res 2004 May; 53 (5): 181-8. 4) Cohen S. et Al. - Treatment of rheumatoid arth- ritis with anakinra, a recombinant human inter- leukin 1 receptor antagonist. Arthritis Rheum.; 2002, 46: 614-624. 5) Daurat V. et Al. - Attività immunomodulante di basse dosi di interferone α e β nel topo. Biomed. Pharmacother; 1988, 42: 197-206. (translated title from French) 6) Davenas E. et Al. - Human basophil degranula- tion triggered by very diluted anti-serum against IgE. Nature; 1988, 333: 816-18. 7) Enbergs H., Arndt G. - Effects of different ho- meophatic potencies of Lachesis on lymphocy- te cultures obtained from rabbit blood. Biol.Tier; 1993, 4. (translated title from German) 8) Enbergs H. - Efficacia dei farmaci omeopatici Suis ed Arnica comp.-Heel® sull'attività dei lin- fociti e dei fagociti. La Med. Biol.; 1998/3, 5-14. 9) Jäggi R. et Al. - Doppia inibizione della 5-li- poossigenasi/cicloossigenasi con un farmaco omeopatico ricostituito. La Med. Biol.; 2005/1, 17-25. 10) Milani L. - I tre cerebrotipi umani: riflessioni sul- la loro funzione neurobiologica. La Med. Biol.; 1994/3, 35-41. 11) Milani L. - Dal fegato vaticinatore alla Nuova Tavola delle Omotossicosi. Dai Punti di Weihe al same-same-but-different nella terapia della steatoepatite non alcoolica. La Med. Biol.; 2006/4, 13-26. 12) Milani L., Buttignol M. - Sulla purezza de “Ma- teria Medica Pura” di Samuel Hahnemann. La Med. Biol.; 2007/2, 47-55. 13) Pennec J.P., Aubin M. - Effect of Aconitum and Veratrum on the isolated perfused heart of com- mon eel (Anguilla anguilla). Comp. Biochem. Physiol, 1984, 776:367-69. 14) Poitevin B. et Al. - The effects of Belladonna and Ferrum phosphoricum on the chemulumine- scence of human poly-morphonuclear neutro- phils. Ann. Homéop. Fr.; 1983, 3: 5-12. (translated title from French) 15) Poitevin B. et Al. - Approccio all'analisi quanti- tativa dell'effetto di Apis mellifica sulla degranu- lazione dei basofili umani coltivati in vitro. Innov. Tech. Biol. Med.; 1986, 7: 64-68. (translated title from French) 16) Poitevin B. et Al. - In vitro immunological degra- nulation of human basophils is modulated by lung histamine and Apis mellifica. Brit. J. Clin. Pharmacol.; 1988, 25: 439-444. 17) Stumpf W.E. - J. Pharmacol. Toxicol. Methods; 2005. 51, (1), 25. 18) Wagner H. et Al. - Actions of homeophatic pre- parations on fagocyte activity of granulocytes. In vitro tests and double blind controlled studies. Arzneim. Forsch./Drug Res.; 1986, 36: 1424- 1425. (translated title from German)
  • 9. 27 PHYSIOLOGICAL REGULATING MEDICINE 1/2007 19) Wagner H. - Studi immunologici in vitro e in vi- vo con farmaci vegetali a bassi dosaggi. Rivista Italiana di Omotossicologica; 1988/3, 13-19. 20) Wagner H. et Al. - Stimolazione in vitro dei lin- fociti e dei granulociti umani mediante quantità espresse in picogrammi e femtogrammi di agen- ti citostatici. Arzneim. Forsch./Drug Res.; 1988, 38: 273-275. (translated title from German) In addition, the following were consulted: 1) Abbas K., Lichtman A.H., Pober J.S. - Cellular and molecular immunology. Saundres Com- pany, Philadelphia; 2000. 2) Bharat B. et Al. - Human cytokines handbook for basic and clinical research. Aggarwal. Jordan u. Guttermann; 1996. 3) Dinarello C.A. - Biological basis for interleukin- 1 in disease. Blood; 87: 2095-2147; 1996. 4) Luster A.D. - Chemokines-chemotactic molecu- les that mediate inflammation. New England Journal of Medicine. 338: 436-445; 1998. 5) Milani L. - Homeomesotherapy for pain mana- gement in primary chronic coxarthrosis with a homeopathic injectable formulation. Physiologi- cal Regulating Medicine, 2006/1; 9-18. ® Tables 1, 2, 5, 6 are original by the Author; Tables 3, 4, are adapted explanations by the Author in relation to the updated bibliography. Author's address Prof. Leonello Milani, MD, PhD - Vice President of A.I.O.T. - Scientific director of “La Medicina Biologica” and “Physiological Regulating Medicine” - Professor h.c. of the Higher Institute of Health Studies, Rome; a collaborative Centre for the WHO - Lecturer and tutor in the School of Homeopathy, Homotoxicology and Integrated Disciplines -Academy of Biological Medicine. Via Vanvitelli 6 I - 20129 Milano