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PHYSIOLOGICAL REGULATING MEDICINE 2011
HOMEOMESOTHERAPY OF THE
PATHOLOGICAL SCARS
SUMMARY
S. Korkunda
RESEARCH AIMS
The aim of this research is to detect indi-
cations and efficiency, using the low
dose preparations Made®
and Guna®
-
Collagen (Guna Laboratories, Milan -
Italy) in mesotherapy on the pathologi-
cal scars of different origin and age in
comparison with traditional methods.
MATERIALS AND METHODS
Patients with pathological scars –
keloids, hypertrophic, and atrophic
scars (KS, HS, AS) – who were treated
at the Kharkiv Burn Center (Kharkiv-
Ukraine) from November 2009 to July
2011, were taken under clinical obser-
vations.
To the first (basic) group belonged
patients with pathological scars of dif-
ferent age which embrace different
areas; these only got mesotherapeutic
treatment with Made®
and Guna®
-
Collagen.
The second group was a control one.
Similar patients received a standard
treatment regimen. The efficiency of
treatment was estimated in accordance
with clinical characteristics of scar tis-
sue, patients’ subjective estimation,
laboratory blood analysis, and histo-
logical study of scar tissue before and
at the end of the treatment.
FINDINGS AND DISCUSSION
᭤ The basic group (30 patients aged be-
tween 10 and 62 years) was treated on-
ly with an intralesional injections
course of the preparations Made®
and
Guna®
-Collagen, 0.5-4 ml/week.
None of the patients was treated with
the compression therapy because of
scars location. The conservative thera-
py of joints desmogenic contracture was
not conducted. The medium term of
treatment was 115 days.
After 2 weeks of treatment the soften-
ing and flattening of HS and KS, the
minimization of vegetative reaction
were noticed; lightening of scar tissue,
disappearance of the scar tissues flab-
biness in patient with AS and color
changes from depigmentation to skin
color were noticed after 4 weeks.
After 2 weeks of treatment all the pa-
tients noticed pain and itch relief sub-
jectively. At the end of the treatment, the
scar tissue is soft, elastic, without any
pathological vegetative reaction and it
can be easily taken into a fold.
In patients with HS and KS the color of
the skin is from flesh to intensive pink
(in case of old KS); in patients with AS
the skin has a flesh color.
The most evident transformation of scar
tissue ensued in patients with fresh scars
(the beginning of treatment not later
than 1-2 months from the start of scar
tissue growth) in a period of 80 days, in
patients with old scars (the first visit took
place 8-12 months from the beginning
The results of this study concerning
homeomesotherapy of the pathological
scars demonstrate the high clinical ef-
ficacy compared to the traditional treat-
ment, such as:
1) Reducing treatment time at the average
by 93-146 days.
2) Reducing the costs of rehabilitation.
3) Achieving the best possible treatment
outcome in the basic group with early
start of treatment.
4) Getting clinically more full-fledged re-
sult, when working with biologically safe
medicines.
5) Determination of laboratory diagnostic
indicators, which make it possible to
control the treatment and make projec-
tions.
6) Identification of new trends in the treat-
ment of patients with pathological scars.
7) Reduction of indication for the further
conservative and surgical rehabilitation.
8) Improving the patients’ quality of life,
and optimization of social rehabilitation.
Mesotherapy of pathological scars with
Made®
and Guna®
-Collagen can achieve
significant functional and aesthetic
results in a shorter period of treatment;
it doesn’t have any complication or neg-
ative side effect, nor any special
requirements for equipment is needed.
The treatment course is not problemat-
ic fot the patients’ life and work activi-
ties, and the treatment helps to improve
their quality of life.
PATHOLOGICAL
SCARS, HOMEOMESOTHERAPY,
COLLAGEN, OXYPROLINE, GAGs,
MADE®
, GUNA®
COLLAGEN
KEY WORDS
23
THERAPEUTICS
From: http://www.scars1.com/gallery/images/3wk_
pre.jpg
Korkunda-A:Art. Del Giudice 15/12/11 09.22 Pagina 23
24
PHYSIOLOGICAL REGULATING MEDICINE 2011
of the scar tissue growth) in a period of
125 days.
Complications and side effects were not
found out; during the treatment proce-
dures the painfulness was moderate.
Clinically the scar tissue, which takes
up a small area, becomes hardly no-
ticeable, similar to the surrounding skin.
The extensive scar tissues slightly differ
in color from the not injured skin, but
functionally they are identical to it; which
shows itself by gaining of motion in the
joints with desmogenic contractures.
᭤ In the control group (15 patients aged
between 14 and 45 years) a standard
anti-scars therapy was performed: com-
pression therapy (elastic pressure band-
ages), ointment Contractubex, physio-
therapy courses, a course of Longidaza
N° 20 intramuscularly, gymnastics, in-
tralesional injections of steroid hor-
mones, sanatorium-and-spa treatment.
The medium term of treatment lasted
218 days.
Clinically, at end of the treatment, the
scar tissue is soft, with low-grade vege-
tative reaction, cannot be taken into a
fold on all the areas of the skin, color
varies from hyperpigmented to intensive
pink. Patients with AS present the fol-
lowing changes: increased flabbiness of
scar tissue, and persistent depigmenta-
tion remains in scars.
In the basic group, according to the
ultrasound scan results before the treat-
ment, the height of hypertrophic and
keloid scars averaged 4.31 mm; the depth
of the atrophic scars was 3.03 mm.
The presence of not uniform irregular-
shaped inclusions with reduced
echogenicity in the scar tissue was di-
agnosed in all the patients; there was
strong flattening or absence of a dermo-
epidermal junction line.
At the end of the treatment the scar
height (HS, KS) averaged 3.43 mm, the
depth of AS averaged 4.2 mm; the or-
der of fibers and the evident dermo-epi-
dermal junction line are observed in the
scars structure. Thereby the height re-
ducing of hypertrophic and keloid scars
averaged 0,872 mm (d < 0,05), and the
depth increase of AS averaged 1,15 mm
(d < 0,05).
Similar results have been observed in
the control group, treatment performed
at the same time, they maintain unim-
portant small difference in indexes
in patients with HS and KS, but they
differ significantly in patients with AS
(TAB. 1).
Thus, when using both the treatments,
the height reducing of HS and KS oc-
curs with a significant small difference;
when treating AS in the basic group of
treatment the volume filling of lost tis-
sue occurs, which is physiologically
positive.
– On the contrary, when treating with
standard methods, the atrophy of the
tissue gets worse.
Morphological examination of biopsy
materials of the old scar tissue in the ba-
sic group before the treatment (100,
200 and 400, hematoxylin eosin stain
and Van Gieson's stain): papillary layer
of dermis became thin, not full-blown,
a tough fibrous connective tissue with
occurrence of hyalinosis in the reticu-
lar dermis; almost complete absence of
vascular component attracts attention –
single large thick-walled vessels with
sclerosis and hyalinosis of their wall.
Reticular layer has a zonal structure
with the presence of beams of tough fi-
brous sclerosed fibers that are random-
ly woven and complete lack of cellular
elements (fibroblasts and fibrocytes);
these bundles are surrounded by a quite
dense and cellular connective tissue
and with a relatively large number of fi-
broblasts and a small amount of thin-
walled vessels. After the treatment the
reticular dermis is presented with a fi-
brous, soft, well vascularized connec-
tive tissue with a small amount of
coarse-fibered collagen.
The basis of well-defined, interlacing
collagen fibers is a large quantity of fi-
broblasts and fibrocytes.
Rather more of them can be observed
around small, thin-walled vessels. In this
case, the morphology of the dermis con-
nective tissue approximates to the struc-
ture of the skin with normal structure.
Morphological research in the control
group was carried out only at the end
of the treatment: hyperkeratosic lami-
nated pavement epithelium, flattening
of dermo-epidermal line, growth of the
coarse sclerosed fibers in the reticular
dermis, poor leucocytic infiltration, iso-
lated vessels, and fibroblasts.
– Histopathologic finding of biopsy in
the control group have expressed dif-
ferences from that in the basic group.
The purpose of the laboratory blood
analysis before and after treatment was
to study the metabolism of the connec-
tive tissue in the process of anti-scars
therapy, by the identification of poten-
Research
Groups
Basic group
Control group
* The differences are significant d < 0,05; ** The differences are significant between the groups.
Before
treatment, mm
After
treatment, mm
Changes in mm %
HS, KS
4,31
4,28
AS
3,03
2,89
HS, KS
3,43*
3,58*
AS
4,2**
2,32*
HS, KS
-0,872**
-20,42%
-0,70*
-16,36%
AS
+1,15**
+38,61%
-0,57*
-19,73%
Pathological scars before and after the treatment. Ultrasound scan results.
TAB. 1
Korkunda-A:Art. Del Giudice 15/12/11 09.22 Pagina 24
25
PHYSIOLOGICAL REGULATING MEDICINE 2011
tial diagnostic indicators of pathologi-
cal process cicatrization activity.
We studied the free and bound
oxyproline, total collagen, gly-
cosaminoglycans (GAGs), vitamin C,
flavin adenine dinucleotide, L-trypto-
phan, core-protein in both groups of
patients, who were receiving treat-
ment of pathological scars (TAB. 2).
Comparison was carried out with infor-
mation about laboratory norms of con-
ventionally healthy people.
One of the main indicators of collagen
metabolism is the content of oxyproline
in the blood.
– Oxyproline (proline derivative) is
one of the collagen basic amino acids;
this allows to consider it as a marker,
which reflects the catabolism of this
protein. About 20% of the peptides,
which contain oxyproline released
from the collagen molecules, are
excreted with the urine.
Only 1% of urine oxyproline is in free
form; the remaining 99% are the pep-
tides’ components.
In case of violation of collagen synthe-
sis the amount of cross-links in collagen
fibrils decreases, which leads to an in-
creased content of easily soluble colla-
gen.Therefore, in patients with impaired
metabolism of the connective tissue, the
excretion of oxyproline increases in
urine, the content of its free fraction in
the blood increases, and the content of
its bound fraction decreases.
– GAGs play an important role in the
transport and exchange of water, salts,
nutrients, and metabolites in tissues.
The study of the structural and meta-
bolic state of the connective tissue
demonstreted high activity of GAGs:
the amount was largely increased in the
blood plasma of patients in the 1st and
in the 2nd group respectively (57,5 ±
2,4 and 49,2 ± 1,3 micromole/l) after
our treatment, 1,5 and 1,2 times higher
- respectively - than the indexes of the
comparison group (conventionally
healthy patients).
– Collagenolytic activity (CLA) had sim-
ilar dynamics and didn’t depend on the
choice of therapeutic method.
The highest CLA values were recorded
in patients with the standard therapy
method (46,8 ± 2,3 micromole of
oxyproline l/h). Levels of plasma CLA
in this group exceeded the data of con-
ventionally healthy patients 7-8 times,
and in the main group of 4-5 times.
Thus this figure can be viewed as one,
which has an important diagnostic and
prognostic value in determining predis-
position to a pathological cicatrization
and, of course, to choose the method of
therapy.
The average of free oxyproline in both
groups before the treatment was 2,17
0,65 micromole/l, while in 12 persons
(41,5%), its concentration was in-
creased, in 8 patients (35,6%) it was re-
duced and in the rest of patients oxypro-
line level was 1,55±0.27 micromole/l,
which fitted the indicators of conven-
tionally healthy people.
Also in the 1st and 2nd group there was
a significant increase of bound oxypro-
line in serum compared to the indica-
tors of control individuals (27,3% and
46,6%), respectively (d < 0,001).
If we take into account that the level of
free oxyproline in the blood serum re-
flects the intensity of the collagen decay,
and the level of a protein-bind oxypro-
line reflects the activity of proliferative
Group
and method
of treatment
1st
Group
(basic) n = 27
2nd
Group
(control) n = 13
Conventionally
healthy people
n = 18
Indexes, M±m
* The differences are significant d < 0,05; ** The differences are significant between the groups.
free oxyproline
millimole/l
bind oxyproline
mole/l
GAGs
micromole/l
CLA (micromole of
oxyproline/l·h)
Before the
treatment
1,32±0,8
2,21±0,5
After the
treatment
1,57±0,3**
2,1±0,2*
Before the
treatment
7,35±1,4
9,5±1,0
After the
treatment
7,7±1,3**
9,2±1,3*
Before the
treatment
52,7±4,3*
41,5±1,9
After the
treatment
57,5±2,4*
49,2±1,3**
Before the
treatment
31,7±3,5
46,8±2,3
After the
treatment
39,6±4,2**
47,4±2,5*
1,49±0,12 6,28±0,19 38,2±1,2 male – 7,3±0,56
female – 7,6±0,43
Dynamic of biochemical parameters in patients with pathological scars, depending on the treatment method.
TAB. 2
Korkunda-A:Art. Del Giudice 15/12/11 09.22 Pagina 25
26
PHYSIOLOGICAL REGULATING MEDICINE 2011
processes in the connective stroma of
the organs (Kaminskaya G., Puryaeva
N.L., 1990; Sodikova N.B, 2002), the
indexes of the above mentioned mark-
ers in the pathogenesis of the patholog-
ical scars formation becomes clear.
The analysis of the research results of
these parameters allows us to get to
the following conclusions: the for-
mation of pathological scars is ac-
companied by profound metabolic
disorders of the connective tissue
and it is confirmed by a significant
increase of collagenolytic activity of
blood serum and glycosaminogly-
cans content in it.
Evaluative studies of oxyproline showed
the most pronounced changes of bind
oxyproline after the treatment, where-
as the rates of free oxyproline were mul-
tidirectional. Almost half of the patients
in the two groups showed an increase
of this index, which indicates an in-
creased level of connective tissue re-
modeling.
In other patients, against the back-
ground of basic therapy, the free
oxyproline levels were low, which - on
the contrary - reflects the reduction in
the intensity of collagen metabolism,
perhaps as a result of the therapy we
carried out.
The GAGs index may be a predictive
criterion for the selection of the thera-
peutic measures. The high correlation
between the dynamics of collagenolyt-
ic activity and the level of bind oxypro-
line of blood plasma allow us to use
them as monitoring criteria for the ef-
fectiveness of the conducted therapy.
Catabolism of the connective tissue is
carried out in the intercellular substance
under the influence of specific en-
zymes: collagenase, elastase, proteas-
es, glycosidases.
Peptide chains of collagen are formed
on polyribosomes, associated with the
membranes of the endoplasmic reticu-
lum (EPR). Simultaneously with the
translation of DNA, hydroxylation of
proline and lysine residues takes place
in peptide chains.
Ascorbic acid acts as a reducing agent,
which contributes to the hydroxylated
iron in the ferrous state.
Hydroxylation of proline is necessary
for the formation of a stable triple helix
structure of collagen. Hydroxylation of
lysine is necessary for the formation of
covalent bonds between molecules of
collagen in the formation of collagen
structures. Hydroxylysine residues are
sites of glycosylation.
– In case of vitamin C deficiency, the
collagen synthesis breaks down at the
stage of hydroxylation. Less strong and
less stable collagen fibers emerge.
As a result of our investigation, we es-
tablished that patients who were in the
basic treatment group had a signifi-
cantly important increase in the level of
vitamin C during the therapy, more than
the control group, and in both groups
without additional treatment (FIG. 1).
Proteins-proteoglycans are called core-
proteins. The protein part of proteogly-
cans, as well as of other secretory pro-
teins, is synthesized on the poliribo-
some EPR.
Peptide chain penetrates the membrane
and grows into the cavity of the EPR.
Here begins the synthesis of gly-
cosaminoglycans and proteoglycans
part. As a result of our study of core-pro-
tein before the treatment, we found out
that there is a qualitative positive reac-
tion in the two studied groups (posi-
tive/positive), whereas in the group of
conventionally healthy people, this re-
action was negative (negative/negative).
On the background of our therapy in
the 1st group submitted to the basic
treatment we saw reaction changes for
negative/positive.
In the 2nd group of patients reaction on
the core-protein remained unchanged
(positive/positive).
Our data indicate the impact of the
treatment on the first reactions of gen-
eration of the carbohydrate component
of proteoglycans, which occurs in the
EPR.
Most of the subsequent stages of gli-
cosamin chains synthesis and their
modifications occur in the Golgi appa-
ratus, where it is much harder to influ-
ence biochemical processes.
In the synthesis of GAGs participate cor-
responding nucleotide derivatives of
monosaccharides and highly specific
glycosyltransferase.To study their effect
we measured levels of FAD+ / FADH2
and copper content in the serum of pa-
tients before and after therapy.
As a result of our study we found out a
violation of metabolism oxidative stage
of connective tissue at the level of
FAD/FADH as mandatory participants
of redox reactions and regulators of tis-
sue respiration in the pentose-phos-
phate pathway, which runs at the mo-
ment of the pathological scars forma-
tion.
In the patients of both groups before the
treatment, an oxidized form increase of
coenzymes of flavin-dependent form.
At a deeper study of bioenergetic
processes in the cell, we analyzed the
ratio of FAD+ and FADH2, as regulators
of the mitochondrial respiratory chain.
In all the groups the reduction of FADH2
(0,0294±0.001 micromole/l) by the
0,45
0,4
0,35
0,3
0,25
0,2
0,15
0,1
0,05
0
Before
treatment
Considered
as healthy
1st
Group 2nd
Group
After
treatment
Vitamin C levels in patients with pathological
scars, depending on the treatment method.
FIG. 1
Korkunda-A:Art. Del Giudice 15/12/11 09.22 Pagina 26
27
PHYSIOLOGICAL REGULATING MEDICINE 2011
control values (0,054±0,005 micro-
mole/l) was observed.
The concentration of FAD+ (0,234±0,13
micromole/l) in both groups was signifi-
cantly higher (d <0,05) than in the group
of healthy patients (TAB. 3; FIGG. 2, 3).
– The correlation grows of FAD+/FADH2
lowers the activity of FADH2 depend-
ent enzymes in the cytosol and mito-
chondria. During the study of these
data before and after our treatment, we
found out that in the first group with
the basic treatment the rates of FAD+
and FADH2 tended to improve, while
in the second group they remained at
the same level.
All this may indicate a reduction of di-
hydroxyacetone phosphate, an inter-
mediate metabolite of glycolysis and
gluconeogenesis, which leads to a rate
reduction of gluconeogenesis and the
starting of the pentose phosphate path-
way, and consequently, to an increased
formation of pathological scars in the
second group of patients.
The growth of FADH2 concentration, in
comparison with FAD+, slows down the
oxidation in the pentose-phosphate
pathway, thereby the ratio of
lactate/pyruvate is increasing, which
further reduces the rate of gluconeoge-
nesis, and increases the lactate con-
centration in blood.
Oxidative decarboxylation of pyruvate is
accompanied by the formation of FADH2
and the kynurenic pathway and its end
products are directly dependened on the
concentration of FAD+, which is involved
in the mitochondrial respiratory chain
and provides the ATP cell.
It is known that the ratio of FAD+/FADH2
in the cell is a relatively stable rate and
that the reduction of FADH2 reduces the
speed of decarboxylation of pyruvate.
Thus, the rate of change in the ratio of
FAD+/FADH2 is an important factor,
which represents the energy needed by
cells to regulate the rate of oxidation in
the mitochondria and being responsible
for the mechanism of the pentose phos-
phate pathway regulation.
Tryptophan is a source of nicotinamide
coenzyme forms (NAD+
and NADP) of
vitamin B5; the tryptophan metabolism
is also associated with the formation of
biogenic monoamine serotonin, hor-
mone melatonin, inducer of cell differ-
entiation and proliferation – 5-hydrox-
yindoleacetic, 5-HIAA (5-hydroxy in-
dolic acid), which are able to influence
considerably the metabolism of various
organs and tissues.
– Analysis of scientific data shows that
the studies of the tryptophan metabo-
lism and pathogenic role of its meta-
bolic products in the mechanisms of
pathological scarring development
have not found the proper reflection in
the scientific literature now available.
This issue is of great scientific interest
to study the pathogenic mechanisms of
pathological scars formation, diagnos-
tic optimization of difficulty degree of
the process of cicatrization and devel-
opment of the appropriate treatment.
It is known that L-tryptophan is the sta-
bilizer of the enzymeTDO (tryptophan-
2, 3-dioxygenase).
It contributes to the formation of a sta-
ble conformational state, the TDO has
an absolute substrate specificity towards
the L-tryptophan and catalyzes the irre-
versible key reaction of amino acid ca-
tabolism in kynurenic pathway of its
metabolism with the formation of N-
formyl-L-kynurenine, and later one of
the key end-metabolites – NAD+
.
– This enzyme accelerates the incorpo-
Before
treatment
Considered
as healthy
1st
Group 2nd
Group
After
treatment
0
0,2
0,1
0,3
0,4
0,5
FAD+ levels in patients with pathological
scarring before and after the treatment.
FIG. 2
Before
treatment
Considered
as healthy
1st
Group 2nd
Group
After
treatment
0
0,02
0,01
0,03
0,04
0,05
0,06
FADH2 levels in patients with pathological
scarring before and after the treatment.
FIG. 3
* The difference is reliable by comparison
with the standard;
* * The difference is reliable between the groups.
Indexes
FAD+
FADH2
FAD+/ FADH2
Standard
0,243±0,13
0,054±0,005
0,09±0,02
1st Group
0,365±0,08*
0,0294±0,001*
0,12±0,035
2 nd Group
0,43±0,2*
0,0267±0,004*
0,15±0,028
The concentration of FAD+ and FADH2 in the serum of patients with pathological scars
(micromole/l) before the treatment.
TAB. 3
Korkunda-A:Art. Del Giudice 15/12/11 09.22 Pagina 27
28
PHYSIOLOGICAL REGULATING MEDICINE 2011
ration of molecular oxygen directly
into the molecule of L-tryptophan and
its catalyzed reaction is a factor which
limites the speed of reaction of the
conversion of the substrate.
The examination has found out the activ-
ity growth of the TDO and the L-trypto-
phan content in the serum in both groups
before the treatment (TAB. 4).
In these metabolic conditions the way of
increased synthesis of NAD+
and NADP+
coenzyme opens, needed to strengthen
the reducing syntheses of tissue differen-
tiation and proliferation.
The regulation of TDO is put into effect
by the feedback of kynurenic pathway fi-
nal products of L-tryptophan NAD+
and
NADP+
metabolism, whereas the en-
zyme activation is associated with an in-
crease of the substrate oxidation content
L-tryptophan.
Positive activators of theTDO enzyme are
Cu2+
ions, hematin, ferriheme and σ-
aminolevulinic acid (σ-ALA). Hemin is a
TDO. A significant increase in the TDO
activity allows to evaluate the reduction
of the protein synthesis function of con-
nective tissue in patients with pathologi-
cal scarring, and particularly about the
disturbance of hemoglobin synthesis,
which caused heme to oxidize by oxy-
gen in hemin, which is a coenzyme acti-
vator of this enzyme, and on the other
hand – the oxidized form of heme
(hemin) inhibits the activity of the mito-
chondrial enzyme σ-aminolevulinic,
which catalyzes the first reaction of heme
synthesis from succinyl-CoA and glycine,
σ- aminolevulinic acid.
The main suppliers of reduced substrates
are the central metabolic pathways – ox-
idative decarboxylation of pyruvic acid
and citric acid cycle.
Both of them are realized in the mito-
chondria matrix.
In the course of this processes reactions
of decarboxylation occur (the most part
of all the carbon dioxide produced in the
cells is produced here). In addition, as al-
ready mentioned, during these process-
es the reactions of substrate dehydro-
genation takes place, the reduced coen-
zyme forms NADP∙H+
and FADH2 are
generated, their hydrogen comes into the
respiratory chain of the internal mito-
chondria membrane, where its oxidation
by oxygen to water and synthesis of ATP
occurs. The growth of NAD+
/NADP,
FAD+
/FADH2 correlation indicates ener-
gy deficit, and it is a signal for the oxida-
tion acceleration in the Krebs cycle.
The main effect of the regulators is di-
rected on the activity of three key en-
zymes: citrate synthase, isocitrate dehy-
drogenase and α-ketoglutarate dehydro-
genase.
During the examination of L-tryptophan
metabolism in both groups before the
treatment, any statistically significant
changes in the dynamics of L-trypto-
phan content in serum and theTDO en-
zyme activity (d <0.05) were not found
out, although the stable dynamics in in-
creasing of L-tryptophan and TDO.
However, against the background of the
conducted therapy the parameters of L-
tryptophan and the enzyme TDO activ-
ity differed significantly in the patients
of the 1st group: they were 55,12 ± 2,3
micromole/l and 38,5 ± 2,1 nanomole
kynurenine/mg of protein∙1 hour for
the L-tryptophan and enzyme TDO ac-
tivity respectively, and in the 2nd group
59,192 ± 2,5 micromole/l and 40,1 ±
2,1 nanomole kynurenine/mg of protein
1 hour.
Analysis of the metabolic rates dynam-
ics of amino acid L-tryptophan metabo-
lism indicates (FIG. 4) that the availabili-
ty of L-tryptophan in serum is a signif-
icant diagnostic indicator of the possi-
ble pathological scarring.
These data confirm clearly the impor-
tant role of neuroendocrinal regulation
in the pathogenesis of pathological
scarring formation. However, the eval-
uation of metabolites of L-tryptophan
metabolism allows to make a predictive
conclusion about the level of activity
or probability of pathological cica-
trization.
Thus, the study of amino acid L-trypto-
* The differences are significant d < 0,05.
Indexes
Patients n = 32
69,18±3,6*
41,6±4,1*
L-tryptophan
(micromole/l)
TDO (nanomole
kynurenine/mg of
protein·1 hour)
Conventionally healthy peopleGroup of
observation, sex
Male
(n = 23)
51,8±2,3
37,5±2,3
Female
(n = 20)
50,5±3,0
35,8±3,4
Indexes of L-tryptophan metabolism in patients of the both groups with pathological scars before
the treatment (M ± m).
TAB. 4
Before
treatment
Considered
as healthy
1st
Group 2nd
Group
After
treatment
0
10
20
30
40
50
60
70
80
L-tryptophan levels in patients with
pathological scars before and after treatment,
according to the treatment groups.
FIG. 4
Korkunda-A:Art. Del Giudice 15/12/11 09.22 Pagina 28
29
PHYSIOLOGICAL REGULATING MEDICINE 2011
phan metabolism makes it possible to
confirm objectively the stage of patho-
logical scar development and monitor
the treatment process.
The monitoring indicators are: the test-
ing of L-tryptophan content in serum
and theTDO enzyme activity, which re-
flects one of the important links in the
structural and metabolic disorders dur-
ing the development of pathological ci-
catrization.
The laboratory study of the indexes of
connective tissue metabolism makes it
possible to optimize the pathogenetic
therapy of pathological scars, namely:
the inclusion of therapeutic and health
promotion programs, which are aimed
at normalization of the neuroendocrine
regulation of L-tryptophan metabolism,
organism detoxification, correction of
metabolic acidosis, increasing the lev-
el of antioxidant protection and inhibi-
tion of oxidative stress, increasing of the
immunological resistance in conjunction
with local impact. The efficiency control
of remedial measures can be realized by
studying the metabolites dynamics of the
amino acid L-tryptophan metabolism,
which has a great prognostic value of the
cicatrization process result.
CONCLUSIONS
The results of ths study demonstrate the
high clinical efficacy of the presented
mesotherapeutic treatment of patholog-
ical scars compared to the traditional
treatment, such as:
1) Reducing treatment time at the average
by 93-146 days.
2) Reducing the costs of rehabilitation.
3) Achieving the best possible treatment
outcome in the basic group with early
start of treatment.
4) Getting clinically more full-fledged re-
sult when working with biologically
safe medicines.
5) Determination of laboratory diagnostic
indicators, which make it possible to
control the treatment and make projec-
tions.
6) Identification of new trends in the treat-
ment of patients with pathological scars.
7) Reduction of indication for the further
conservative and surgical rehabilitation.
8) Improving the patients’ quality of life,
and optimization of social rehabilita-
tion.
Mesotherapy of pathological scars
with Made®
and Guna®
-Collagen can
achieve significant functional and aes-
thetic results in a shorter period of
treatment; it doesn’t have any compli-
cations or negative side effect, nor any
special requirements for equipment is
needed.
The treatment course is not problem-
atic for the patients’ life and work ac-
tivities, and treatment results to im-
prove the quality of life. í
author’s address
Dr. Svetlana Korkunda, PhD.
– Docent in the Department of Com-
bustiology, Reconstructive, and
Plastic Surgery of KhMAPE.
Kharkiv City Hospital Emergency
Medical Care.
Kharkiv - Ukraine
Korkunda-A:Art. Del Giudice 15/12/11 09.22 Pagina 29

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Tratamiento de homeomesoterapia en cicatrices con Guna

  • 1. PHYSIOLOGICAL REGULATING MEDICINE 2011 HOMEOMESOTHERAPY OF THE PATHOLOGICAL SCARS SUMMARY S. Korkunda RESEARCH AIMS The aim of this research is to detect indi- cations and efficiency, using the low dose preparations Made® and Guna® - Collagen (Guna Laboratories, Milan - Italy) in mesotherapy on the pathologi- cal scars of different origin and age in comparison with traditional methods. MATERIALS AND METHODS Patients with pathological scars – keloids, hypertrophic, and atrophic scars (KS, HS, AS) – who were treated at the Kharkiv Burn Center (Kharkiv- Ukraine) from November 2009 to July 2011, were taken under clinical obser- vations. To the first (basic) group belonged patients with pathological scars of dif- ferent age which embrace different areas; these only got mesotherapeutic treatment with Made® and Guna® - Collagen. The second group was a control one. Similar patients received a standard treatment regimen. The efficiency of treatment was estimated in accordance with clinical characteristics of scar tis- sue, patients’ subjective estimation, laboratory blood analysis, and histo- logical study of scar tissue before and at the end of the treatment. FINDINGS AND DISCUSSION ᭤ The basic group (30 patients aged be- tween 10 and 62 years) was treated on- ly with an intralesional injections course of the preparations Made® and Guna® -Collagen, 0.5-4 ml/week. None of the patients was treated with the compression therapy because of scars location. The conservative thera- py of joints desmogenic contracture was not conducted. The medium term of treatment was 115 days. After 2 weeks of treatment the soften- ing and flattening of HS and KS, the minimization of vegetative reaction were noticed; lightening of scar tissue, disappearance of the scar tissues flab- biness in patient with AS and color changes from depigmentation to skin color were noticed after 4 weeks. After 2 weeks of treatment all the pa- tients noticed pain and itch relief sub- jectively. At the end of the treatment, the scar tissue is soft, elastic, without any pathological vegetative reaction and it can be easily taken into a fold. In patients with HS and KS the color of the skin is from flesh to intensive pink (in case of old KS); in patients with AS the skin has a flesh color. The most evident transformation of scar tissue ensued in patients with fresh scars (the beginning of treatment not later than 1-2 months from the start of scar tissue growth) in a period of 80 days, in patients with old scars (the first visit took place 8-12 months from the beginning The results of this study concerning homeomesotherapy of the pathological scars demonstrate the high clinical ef- ficacy compared to the traditional treat- ment, such as: 1) Reducing treatment time at the average by 93-146 days. 2) Reducing the costs of rehabilitation. 3) Achieving the best possible treatment outcome in the basic group with early start of treatment. 4) Getting clinically more full-fledged re- sult, when working with biologically safe medicines. 5) Determination of laboratory diagnostic indicators, which make it possible to control the treatment and make projec- tions. 6) Identification of new trends in the treat- ment of patients with pathological scars. 7) Reduction of indication for the further conservative and surgical rehabilitation. 8) Improving the patients’ quality of life, and optimization of social rehabilitation. Mesotherapy of pathological scars with Made® and Guna® -Collagen can achieve significant functional and aesthetic results in a shorter period of treatment; it doesn’t have any complication or neg- ative side effect, nor any special requirements for equipment is needed. The treatment course is not problemat- ic fot the patients’ life and work activi- ties, and the treatment helps to improve their quality of life. PATHOLOGICAL SCARS, HOMEOMESOTHERAPY, COLLAGEN, OXYPROLINE, GAGs, MADE® , GUNA® COLLAGEN KEY WORDS 23 THERAPEUTICS From: http://www.scars1.com/gallery/images/3wk_ pre.jpg Korkunda-A:Art. Del Giudice 15/12/11 09.22 Pagina 23
  • 2. 24 PHYSIOLOGICAL REGULATING MEDICINE 2011 of the scar tissue growth) in a period of 125 days. Complications and side effects were not found out; during the treatment proce- dures the painfulness was moderate. Clinically the scar tissue, which takes up a small area, becomes hardly no- ticeable, similar to the surrounding skin. The extensive scar tissues slightly differ in color from the not injured skin, but functionally they are identical to it; which shows itself by gaining of motion in the joints with desmogenic contractures. ᭤ In the control group (15 patients aged between 14 and 45 years) a standard anti-scars therapy was performed: com- pression therapy (elastic pressure band- ages), ointment Contractubex, physio- therapy courses, a course of Longidaza N° 20 intramuscularly, gymnastics, in- tralesional injections of steroid hor- mones, sanatorium-and-spa treatment. The medium term of treatment lasted 218 days. Clinically, at end of the treatment, the scar tissue is soft, with low-grade vege- tative reaction, cannot be taken into a fold on all the areas of the skin, color varies from hyperpigmented to intensive pink. Patients with AS present the fol- lowing changes: increased flabbiness of scar tissue, and persistent depigmenta- tion remains in scars. In the basic group, according to the ultrasound scan results before the treat- ment, the height of hypertrophic and keloid scars averaged 4.31 mm; the depth of the atrophic scars was 3.03 mm. The presence of not uniform irregular- shaped inclusions with reduced echogenicity in the scar tissue was di- agnosed in all the patients; there was strong flattening or absence of a dermo- epidermal junction line. At the end of the treatment the scar height (HS, KS) averaged 3.43 mm, the depth of AS averaged 4.2 mm; the or- der of fibers and the evident dermo-epi- dermal junction line are observed in the scars structure. Thereby the height re- ducing of hypertrophic and keloid scars averaged 0,872 mm (d < 0,05), and the depth increase of AS averaged 1,15 mm (d < 0,05). Similar results have been observed in the control group, treatment performed at the same time, they maintain unim- portant small difference in indexes in patients with HS and KS, but they differ significantly in patients with AS (TAB. 1). Thus, when using both the treatments, the height reducing of HS and KS oc- curs with a significant small difference; when treating AS in the basic group of treatment the volume filling of lost tis- sue occurs, which is physiologically positive. – On the contrary, when treating with standard methods, the atrophy of the tissue gets worse. Morphological examination of biopsy materials of the old scar tissue in the ba- sic group before the treatment (100, 200 and 400, hematoxylin eosin stain and Van Gieson's stain): papillary layer of dermis became thin, not full-blown, a tough fibrous connective tissue with occurrence of hyalinosis in the reticu- lar dermis; almost complete absence of vascular component attracts attention – single large thick-walled vessels with sclerosis and hyalinosis of their wall. Reticular layer has a zonal structure with the presence of beams of tough fi- brous sclerosed fibers that are random- ly woven and complete lack of cellular elements (fibroblasts and fibrocytes); these bundles are surrounded by a quite dense and cellular connective tissue and with a relatively large number of fi- broblasts and a small amount of thin- walled vessels. After the treatment the reticular dermis is presented with a fi- brous, soft, well vascularized connec- tive tissue with a small amount of coarse-fibered collagen. The basis of well-defined, interlacing collagen fibers is a large quantity of fi- broblasts and fibrocytes. Rather more of them can be observed around small, thin-walled vessels. In this case, the morphology of the dermis con- nective tissue approximates to the struc- ture of the skin with normal structure. Morphological research in the control group was carried out only at the end of the treatment: hyperkeratosic lami- nated pavement epithelium, flattening of dermo-epidermal line, growth of the coarse sclerosed fibers in the reticular dermis, poor leucocytic infiltration, iso- lated vessels, and fibroblasts. – Histopathologic finding of biopsy in the control group have expressed dif- ferences from that in the basic group. The purpose of the laboratory blood analysis before and after treatment was to study the metabolism of the connec- tive tissue in the process of anti-scars therapy, by the identification of poten- Research Groups Basic group Control group * The differences are significant d < 0,05; ** The differences are significant between the groups. Before treatment, mm After treatment, mm Changes in mm % HS, KS 4,31 4,28 AS 3,03 2,89 HS, KS 3,43* 3,58* AS 4,2** 2,32* HS, KS -0,872** -20,42% -0,70* -16,36% AS +1,15** +38,61% -0,57* -19,73% Pathological scars before and after the treatment. Ultrasound scan results. TAB. 1 Korkunda-A:Art. Del Giudice 15/12/11 09.22 Pagina 24
  • 3. 25 PHYSIOLOGICAL REGULATING MEDICINE 2011 tial diagnostic indicators of pathologi- cal process cicatrization activity. We studied the free and bound oxyproline, total collagen, gly- cosaminoglycans (GAGs), vitamin C, flavin adenine dinucleotide, L-trypto- phan, core-protein in both groups of patients, who were receiving treat- ment of pathological scars (TAB. 2). Comparison was carried out with infor- mation about laboratory norms of con- ventionally healthy people. One of the main indicators of collagen metabolism is the content of oxyproline in the blood. – Oxyproline (proline derivative) is one of the collagen basic amino acids; this allows to consider it as a marker, which reflects the catabolism of this protein. About 20% of the peptides, which contain oxyproline released from the collagen molecules, are excreted with the urine. Only 1% of urine oxyproline is in free form; the remaining 99% are the pep- tides’ components. In case of violation of collagen synthe- sis the amount of cross-links in collagen fibrils decreases, which leads to an in- creased content of easily soluble colla- gen.Therefore, in patients with impaired metabolism of the connective tissue, the excretion of oxyproline increases in urine, the content of its free fraction in the blood increases, and the content of its bound fraction decreases. – GAGs play an important role in the transport and exchange of water, salts, nutrients, and metabolites in tissues. The study of the structural and meta- bolic state of the connective tissue demonstreted high activity of GAGs: the amount was largely increased in the blood plasma of patients in the 1st and in the 2nd group respectively (57,5 ± 2,4 and 49,2 ± 1,3 micromole/l) after our treatment, 1,5 and 1,2 times higher - respectively - than the indexes of the comparison group (conventionally healthy patients). – Collagenolytic activity (CLA) had sim- ilar dynamics and didn’t depend on the choice of therapeutic method. The highest CLA values were recorded in patients with the standard therapy method (46,8 ± 2,3 micromole of oxyproline l/h). Levels of plasma CLA in this group exceeded the data of con- ventionally healthy patients 7-8 times, and in the main group of 4-5 times. Thus this figure can be viewed as one, which has an important diagnostic and prognostic value in determining predis- position to a pathological cicatrization and, of course, to choose the method of therapy. The average of free oxyproline in both groups before the treatment was 2,17 0,65 micromole/l, while in 12 persons (41,5%), its concentration was in- creased, in 8 patients (35,6%) it was re- duced and in the rest of patients oxypro- line level was 1,55±0.27 micromole/l, which fitted the indicators of conven- tionally healthy people. Also in the 1st and 2nd group there was a significant increase of bound oxypro- line in serum compared to the indica- tors of control individuals (27,3% and 46,6%), respectively (d < 0,001). If we take into account that the level of free oxyproline in the blood serum re- flects the intensity of the collagen decay, and the level of a protein-bind oxypro- line reflects the activity of proliferative Group and method of treatment 1st Group (basic) n = 27 2nd Group (control) n = 13 Conventionally healthy people n = 18 Indexes, M±m * The differences are significant d < 0,05; ** The differences are significant between the groups. free oxyproline millimole/l bind oxyproline mole/l GAGs micromole/l CLA (micromole of oxyproline/l·h) Before the treatment 1,32±0,8 2,21±0,5 After the treatment 1,57±0,3** 2,1±0,2* Before the treatment 7,35±1,4 9,5±1,0 After the treatment 7,7±1,3** 9,2±1,3* Before the treatment 52,7±4,3* 41,5±1,9 After the treatment 57,5±2,4* 49,2±1,3** Before the treatment 31,7±3,5 46,8±2,3 After the treatment 39,6±4,2** 47,4±2,5* 1,49±0,12 6,28±0,19 38,2±1,2 male – 7,3±0,56 female – 7,6±0,43 Dynamic of biochemical parameters in patients with pathological scars, depending on the treatment method. TAB. 2 Korkunda-A:Art. Del Giudice 15/12/11 09.22 Pagina 25
  • 4. 26 PHYSIOLOGICAL REGULATING MEDICINE 2011 processes in the connective stroma of the organs (Kaminskaya G., Puryaeva N.L., 1990; Sodikova N.B, 2002), the indexes of the above mentioned mark- ers in the pathogenesis of the patholog- ical scars formation becomes clear. The analysis of the research results of these parameters allows us to get to the following conclusions: the for- mation of pathological scars is ac- companied by profound metabolic disorders of the connective tissue and it is confirmed by a significant increase of collagenolytic activity of blood serum and glycosaminogly- cans content in it. Evaluative studies of oxyproline showed the most pronounced changes of bind oxyproline after the treatment, where- as the rates of free oxyproline were mul- tidirectional. Almost half of the patients in the two groups showed an increase of this index, which indicates an in- creased level of connective tissue re- modeling. In other patients, against the back- ground of basic therapy, the free oxyproline levels were low, which - on the contrary - reflects the reduction in the intensity of collagen metabolism, perhaps as a result of the therapy we carried out. The GAGs index may be a predictive criterion for the selection of the thera- peutic measures. The high correlation between the dynamics of collagenolyt- ic activity and the level of bind oxypro- line of blood plasma allow us to use them as monitoring criteria for the ef- fectiveness of the conducted therapy. Catabolism of the connective tissue is carried out in the intercellular substance under the influence of specific en- zymes: collagenase, elastase, proteas- es, glycosidases. Peptide chains of collagen are formed on polyribosomes, associated with the membranes of the endoplasmic reticu- lum (EPR). Simultaneously with the translation of DNA, hydroxylation of proline and lysine residues takes place in peptide chains. Ascorbic acid acts as a reducing agent, which contributes to the hydroxylated iron in the ferrous state. Hydroxylation of proline is necessary for the formation of a stable triple helix structure of collagen. Hydroxylation of lysine is necessary for the formation of covalent bonds between molecules of collagen in the formation of collagen structures. Hydroxylysine residues are sites of glycosylation. – In case of vitamin C deficiency, the collagen synthesis breaks down at the stage of hydroxylation. Less strong and less stable collagen fibers emerge. As a result of our investigation, we es- tablished that patients who were in the basic treatment group had a signifi- cantly important increase in the level of vitamin C during the therapy, more than the control group, and in both groups without additional treatment (FIG. 1). Proteins-proteoglycans are called core- proteins. The protein part of proteogly- cans, as well as of other secretory pro- teins, is synthesized on the poliribo- some EPR. Peptide chain penetrates the membrane and grows into the cavity of the EPR. Here begins the synthesis of gly- cosaminoglycans and proteoglycans part. As a result of our study of core-pro- tein before the treatment, we found out that there is a qualitative positive reac- tion in the two studied groups (posi- tive/positive), whereas in the group of conventionally healthy people, this re- action was negative (negative/negative). On the background of our therapy in the 1st group submitted to the basic treatment we saw reaction changes for negative/positive. In the 2nd group of patients reaction on the core-protein remained unchanged (positive/positive). Our data indicate the impact of the treatment on the first reactions of gen- eration of the carbohydrate component of proteoglycans, which occurs in the EPR. Most of the subsequent stages of gli- cosamin chains synthesis and their modifications occur in the Golgi appa- ratus, where it is much harder to influ- ence biochemical processes. In the synthesis of GAGs participate cor- responding nucleotide derivatives of monosaccharides and highly specific glycosyltransferase.To study their effect we measured levels of FAD+ / FADH2 and copper content in the serum of pa- tients before and after therapy. As a result of our study we found out a violation of metabolism oxidative stage of connective tissue at the level of FAD/FADH as mandatory participants of redox reactions and regulators of tis- sue respiration in the pentose-phos- phate pathway, which runs at the mo- ment of the pathological scars forma- tion. In the patients of both groups before the treatment, an oxidized form increase of coenzymes of flavin-dependent form. At a deeper study of bioenergetic processes in the cell, we analyzed the ratio of FAD+ and FADH2, as regulators of the mitochondrial respiratory chain. In all the groups the reduction of FADH2 (0,0294±0.001 micromole/l) by the 0,45 0,4 0,35 0,3 0,25 0,2 0,15 0,1 0,05 0 Before treatment Considered as healthy 1st Group 2nd Group After treatment Vitamin C levels in patients with pathological scars, depending on the treatment method. FIG. 1 Korkunda-A:Art. Del Giudice 15/12/11 09.22 Pagina 26
  • 5. 27 PHYSIOLOGICAL REGULATING MEDICINE 2011 control values (0,054±0,005 micro- mole/l) was observed. The concentration of FAD+ (0,234±0,13 micromole/l) in both groups was signifi- cantly higher (d <0,05) than in the group of healthy patients (TAB. 3; FIGG. 2, 3). – The correlation grows of FAD+/FADH2 lowers the activity of FADH2 depend- ent enzymes in the cytosol and mito- chondria. During the study of these data before and after our treatment, we found out that in the first group with the basic treatment the rates of FAD+ and FADH2 tended to improve, while in the second group they remained at the same level. All this may indicate a reduction of di- hydroxyacetone phosphate, an inter- mediate metabolite of glycolysis and gluconeogenesis, which leads to a rate reduction of gluconeogenesis and the starting of the pentose phosphate path- way, and consequently, to an increased formation of pathological scars in the second group of patients. The growth of FADH2 concentration, in comparison with FAD+, slows down the oxidation in the pentose-phosphate pathway, thereby the ratio of lactate/pyruvate is increasing, which further reduces the rate of gluconeoge- nesis, and increases the lactate con- centration in blood. Oxidative decarboxylation of pyruvate is accompanied by the formation of FADH2 and the kynurenic pathway and its end products are directly dependened on the concentration of FAD+, which is involved in the mitochondrial respiratory chain and provides the ATP cell. It is known that the ratio of FAD+/FADH2 in the cell is a relatively stable rate and that the reduction of FADH2 reduces the speed of decarboxylation of pyruvate. Thus, the rate of change in the ratio of FAD+/FADH2 is an important factor, which represents the energy needed by cells to regulate the rate of oxidation in the mitochondria and being responsible for the mechanism of the pentose phos- phate pathway regulation. Tryptophan is a source of nicotinamide coenzyme forms (NAD+ and NADP) of vitamin B5; the tryptophan metabolism is also associated with the formation of biogenic monoamine serotonin, hor- mone melatonin, inducer of cell differ- entiation and proliferation – 5-hydrox- yindoleacetic, 5-HIAA (5-hydroxy in- dolic acid), which are able to influence considerably the metabolism of various organs and tissues. – Analysis of scientific data shows that the studies of the tryptophan metabo- lism and pathogenic role of its meta- bolic products in the mechanisms of pathological scarring development have not found the proper reflection in the scientific literature now available. This issue is of great scientific interest to study the pathogenic mechanisms of pathological scars formation, diagnos- tic optimization of difficulty degree of the process of cicatrization and devel- opment of the appropriate treatment. It is known that L-tryptophan is the sta- bilizer of the enzymeTDO (tryptophan- 2, 3-dioxygenase). It contributes to the formation of a sta- ble conformational state, the TDO has an absolute substrate specificity towards the L-tryptophan and catalyzes the irre- versible key reaction of amino acid ca- tabolism in kynurenic pathway of its metabolism with the formation of N- formyl-L-kynurenine, and later one of the key end-metabolites – NAD+ . – This enzyme accelerates the incorpo- Before treatment Considered as healthy 1st Group 2nd Group After treatment 0 0,2 0,1 0,3 0,4 0,5 FAD+ levels in patients with pathological scarring before and after the treatment. FIG. 2 Before treatment Considered as healthy 1st Group 2nd Group After treatment 0 0,02 0,01 0,03 0,04 0,05 0,06 FADH2 levels in patients with pathological scarring before and after the treatment. FIG. 3 * The difference is reliable by comparison with the standard; * * The difference is reliable between the groups. Indexes FAD+ FADH2 FAD+/ FADH2 Standard 0,243±0,13 0,054±0,005 0,09±0,02 1st Group 0,365±0,08* 0,0294±0,001* 0,12±0,035 2 nd Group 0,43±0,2* 0,0267±0,004* 0,15±0,028 The concentration of FAD+ and FADH2 in the serum of patients with pathological scars (micromole/l) before the treatment. TAB. 3 Korkunda-A:Art. Del Giudice 15/12/11 09.22 Pagina 27
  • 6. 28 PHYSIOLOGICAL REGULATING MEDICINE 2011 ration of molecular oxygen directly into the molecule of L-tryptophan and its catalyzed reaction is a factor which limites the speed of reaction of the conversion of the substrate. The examination has found out the activ- ity growth of the TDO and the L-trypto- phan content in the serum in both groups before the treatment (TAB. 4). In these metabolic conditions the way of increased synthesis of NAD+ and NADP+ coenzyme opens, needed to strengthen the reducing syntheses of tissue differen- tiation and proliferation. The regulation of TDO is put into effect by the feedback of kynurenic pathway fi- nal products of L-tryptophan NAD+ and NADP+ metabolism, whereas the en- zyme activation is associated with an in- crease of the substrate oxidation content L-tryptophan. Positive activators of theTDO enzyme are Cu2+ ions, hematin, ferriheme and σ- aminolevulinic acid (σ-ALA). Hemin is a TDO. A significant increase in the TDO activity allows to evaluate the reduction of the protein synthesis function of con- nective tissue in patients with pathologi- cal scarring, and particularly about the disturbance of hemoglobin synthesis, which caused heme to oxidize by oxy- gen in hemin, which is a coenzyme acti- vator of this enzyme, and on the other hand – the oxidized form of heme (hemin) inhibits the activity of the mito- chondrial enzyme σ-aminolevulinic, which catalyzes the first reaction of heme synthesis from succinyl-CoA and glycine, σ- aminolevulinic acid. The main suppliers of reduced substrates are the central metabolic pathways – ox- idative decarboxylation of pyruvic acid and citric acid cycle. Both of them are realized in the mito- chondria matrix. In the course of this processes reactions of decarboxylation occur (the most part of all the carbon dioxide produced in the cells is produced here). In addition, as al- ready mentioned, during these process- es the reactions of substrate dehydro- genation takes place, the reduced coen- zyme forms NADP∙H+ and FADH2 are generated, their hydrogen comes into the respiratory chain of the internal mito- chondria membrane, where its oxidation by oxygen to water and synthesis of ATP occurs. The growth of NAD+ /NADP, FAD+ /FADH2 correlation indicates ener- gy deficit, and it is a signal for the oxida- tion acceleration in the Krebs cycle. The main effect of the regulators is di- rected on the activity of three key en- zymes: citrate synthase, isocitrate dehy- drogenase and α-ketoglutarate dehydro- genase. During the examination of L-tryptophan metabolism in both groups before the treatment, any statistically significant changes in the dynamics of L-trypto- phan content in serum and theTDO en- zyme activity (d <0.05) were not found out, although the stable dynamics in in- creasing of L-tryptophan and TDO. However, against the background of the conducted therapy the parameters of L- tryptophan and the enzyme TDO activ- ity differed significantly in the patients of the 1st group: they were 55,12 ± 2,3 micromole/l and 38,5 ± 2,1 nanomole kynurenine/mg of protein∙1 hour for the L-tryptophan and enzyme TDO ac- tivity respectively, and in the 2nd group 59,192 ± 2,5 micromole/l and 40,1 ± 2,1 nanomole kynurenine/mg of protein 1 hour. Analysis of the metabolic rates dynam- ics of amino acid L-tryptophan metabo- lism indicates (FIG. 4) that the availabili- ty of L-tryptophan in serum is a signif- icant diagnostic indicator of the possi- ble pathological scarring. These data confirm clearly the impor- tant role of neuroendocrinal regulation in the pathogenesis of pathological scarring formation. However, the eval- uation of metabolites of L-tryptophan metabolism allows to make a predictive conclusion about the level of activity or probability of pathological cica- trization. Thus, the study of amino acid L-trypto- * The differences are significant d < 0,05. Indexes Patients n = 32 69,18±3,6* 41,6±4,1* L-tryptophan (micromole/l) TDO (nanomole kynurenine/mg of protein·1 hour) Conventionally healthy peopleGroup of observation, sex Male (n = 23) 51,8±2,3 37,5±2,3 Female (n = 20) 50,5±3,0 35,8±3,4 Indexes of L-tryptophan metabolism in patients of the both groups with pathological scars before the treatment (M ± m). TAB. 4 Before treatment Considered as healthy 1st Group 2nd Group After treatment 0 10 20 30 40 50 60 70 80 L-tryptophan levels in patients with pathological scars before and after treatment, according to the treatment groups. FIG. 4 Korkunda-A:Art. Del Giudice 15/12/11 09.22 Pagina 28
  • 7. 29 PHYSIOLOGICAL REGULATING MEDICINE 2011 phan metabolism makes it possible to confirm objectively the stage of patho- logical scar development and monitor the treatment process. The monitoring indicators are: the test- ing of L-tryptophan content in serum and theTDO enzyme activity, which re- flects one of the important links in the structural and metabolic disorders dur- ing the development of pathological ci- catrization. The laboratory study of the indexes of connective tissue metabolism makes it possible to optimize the pathogenetic therapy of pathological scars, namely: the inclusion of therapeutic and health promotion programs, which are aimed at normalization of the neuroendocrine regulation of L-tryptophan metabolism, organism detoxification, correction of metabolic acidosis, increasing the lev- el of antioxidant protection and inhibi- tion of oxidative stress, increasing of the immunological resistance in conjunction with local impact. The efficiency control of remedial measures can be realized by studying the metabolites dynamics of the amino acid L-tryptophan metabolism, which has a great prognostic value of the cicatrization process result. CONCLUSIONS The results of ths study demonstrate the high clinical efficacy of the presented mesotherapeutic treatment of patholog- ical scars compared to the traditional treatment, such as: 1) Reducing treatment time at the average by 93-146 days. 2) Reducing the costs of rehabilitation. 3) Achieving the best possible treatment outcome in the basic group with early start of treatment. 4) Getting clinically more full-fledged re- sult when working with biologically safe medicines. 5) Determination of laboratory diagnostic indicators, which make it possible to control the treatment and make projec- tions. 6) Identification of new trends in the treat- ment of patients with pathological scars. 7) Reduction of indication for the further conservative and surgical rehabilitation. 8) Improving the patients’ quality of life, and optimization of social rehabilita- tion. Mesotherapy of pathological scars with Made® and Guna® -Collagen can achieve significant functional and aes- thetic results in a shorter period of treatment; it doesn’t have any compli- cations or negative side effect, nor any special requirements for equipment is needed. The treatment course is not problem- atic for the patients’ life and work ac- tivities, and treatment results to im- prove the quality of life. í author’s address Dr. Svetlana Korkunda, PhD. – Docent in the Department of Com- bustiology, Reconstructive, and Plastic Surgery of KhMAPE. Kharkiv City Hospital Emergency Medical Care. Kharkiv - Ukraine Korkunda-A:Art. Del Giudice 15/12/11 09.22 Pagina 29