7
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

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Page 1: HOMEOMESOTHERAPY OF THE · ages), ointment Contractubex, physio-therapy courses, a course of Longidaza N° 20 intramuscularly, gymnastics, in-tralesional injections of steroid hor-mones,

PHYSIOLOGICAL REGULATING MEDIC INE 2011

HOMEOMESOTHERAPY OF THEPATHOLOGICAL SCARS

SUMMARY

S. Korkunda

RESEARCH AIMS

The aim of this research is to detect indi-cations and efficiency, using the lowdose preparations Made® and Guna®-Collagen (Guna Laboratories, Milan -Italy) in mesotherapy on the pathologi-cal scars of different origin and age incomparison with traditional methods.

MATERIALS AND METHODS

Patients with pathological scars –keloids, hypertrophic, and atrophicscars (KS, HS, AS) – who were treatedat the Kharkiv Burn Center (Kharkiv-Ukraine) from November 2009 to July2011, were taken under clinical obser-vations.

To the first (basic) group belongedpatients with pathological scars of dif-ferent age which embrace differentareas; these only got mesotherapeutictreatment with Made® and Guna®-Collagen.

The second group was a control one.Similar patients received a standardtreatment regimen. The efficiency oftreatment was estimated in accordancewith clinical characteristics of scar tis-sue, patients’ subjective estimation,laboratory blood analysis, and histo-logical study of scar tissue before andat 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 injectionscourse of the preparations Made® andGuna®-Collagen, 0.5-4 ml/week. None of the patients was treated withthe compression therapy because ofscars location. The conservative thera-py of joints desmogenic contracture wasnot conducted. The medium term oftreatment was 115 days. After 2 weeks of treatment the soften-ing and flattening of HS and KS, theminimization of vegetative reactionwere noticed; lightening of scar tissue,disappearance of the scar tissues flab-biness in patient with AS and colorchanges from depigmentation to skincolor 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, thescar tissue is soft, elastic, without anypathological vegetative reaction and itcan be easily taken into a fold. In patients with HS and KS the color ofthe skin is from flesh to intensive pink(in case of old KS); in patients with ASthe skin has a flesh color. The most evident transformation of scartissue ensued in patients with fresh scars(the beginning of treatment not laterthan 1-2 months from the start of scartissue growth) in a period of 80 days, inpatients with old scars (the first visit tookplace 8-12 months from the beginning

The results of this study concerninghomeomesotherapy of the pathologicalscars demonstrate the high clinical ef-ficacy compared to the traditional treat-ment, such as:

1) Reducing treatment time at the averageby 93-146 days.

2) Reducing the costs of rehabilitation.3) Achieving the best possible treatmentoutcome in the basic group with earlystart of treatment.

4) Getting clinically more full-fledged re-sult, when working with biologically safemedicines.

5) Determination of laboratory diagnosticindicators, which make it possible tocontrol 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 furtherconservative and surgical rehabilitation.

8) Improving the patients’ quality of life,and optimization of social rehabilitation.

Mesotherapy of pathological scars withMade® and Guna®-Collagen can achievesignificant 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 improvetheir quality of life.

PATHOLOGICALSCARS, HOMEOMESOTHERAPY, COLLAGEN, OXYPROLINE, GAGs,MADE®, GUNA® COLLAGEN

KEY WORDS

23

THERAPEUTIC

S

From: http://www.scars1.com/gallery/images/3wk_pre.jpg

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PHYSIOLOGICAL REGULATING MEDIC INE 2011

of the scar tissue growth) in a period of125 days. Complications and side effects were notfound out; during the treatment proce-dures the painfulness was moderate. Clinically the scar tissue, which takesup a small area, becomes hardly no-ticeable, similar to the surrounding skin.The extensive scar tissues slightly differin color from the not injured skin, butfunctionally they are identical to it; whichshows itself by gaining of motion in thejoints with desmogenic contractures.

� In the control group (15 patients agedbetween 14 and 45 years) a standardanti-scars therapy was performed: com-pression therapy (elastic pressure band-ages), ointment Contractubex, physio-therapy courses, a course of LongidazaN° 20 intramuscularly, gymnastics, in-tralesional injections of steroid hor-mones, sanatorium-and-spa treatment.

The medium term of treatment lasted218 days. Clinically, at end of the treatment, thescar tissue is soft, with low-grade vege-tative reaction, cannot be taken into afold on all the areas of the skin, colorvaries from hyperpigmented to intensivepink. Patients with AS present the fol-lowing changes: increased flabbiness ofscar 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 andkeloid scars averaged 4.31 mm; the depthof the atrophic scars was 3.03 mm. The presence of not uniform irregular-shaped inclusions with reducedechogenicity in the scar tissue was di-agnosed in all the patients; there wasstrong flattening or absence of a dermo-epidermal junction line. At the end of the treatment the scarheight (HS, KS) averaged 3.43 mm, thedepth of AS averaged 4.2 mm; the or-der of fibers and the evident dermo-epi-dermal junction line are observed in thescars structure. Thereby the height re-ducing of hypertrophic and keloid scars

averaged 0,872 mm (d < 0,05), and thedepth increase of AS averaged 1,15 mm(d < 0,05).

Similar results have been observed inthe control group, treatment performedat 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 oftreatment the volume filling of lost tis-sue occurs, which is physiologicallypositive. – On the contrary, when treating withstandard methods, the atrophy of thetissue gets worse.

Morphological examination of biopsymaterials of the old scar tissue in the ba-sic group before the treatment (100,200 and 400, hematoxylin eosin stainand Van Gieson's stain): papillary layerof dermis became thin, not full-blown,a tough fibrous connective tissue withoccurrence of hyalinosis in the reticu-lar dermis; almost complete absence ofvascular component attracts attention –single large thick-walled vessels withsclerosis and hyalinosis of their wall.Reticular layer has a zonal structurewith the presence of beams of tough fi-brous sclerosed fibers that are random-

ly woven and complete lack of cellularelements (fibroblasts and fibrocytes);these bundles are surrounded by a quitedense and cellular connective tissueand with a relatively large number of fi-broblasts and a small amount of thin-walled vessels. After the treatment thereticular dermis is presented with a fi-brous, soft, well vascularized connec-tive tissue with a small amount ofcoarse-fibered collagen.

The basis of well-defined, interlacingcollagen fibers is a large quantity of fi-broblasts and fibrocytes. Rather more of them can be observedaround small, thin-walled vessels. In thiscase, the morphology of the dermis con-nective tissue approximates to the struc-ture of the skin with normal structure.

Morphological research in the controlgroup was carried out only at the endof the treatment: hyperkeratosic lami-nated pavement epithelium, flatteningof dermo-epidermal line, growth of thecoarse sclerosed fibers in the reticulardermis, poor leucocytic infiltration, iso-lated vessels, and fibroblasts. – Histopathologic finding of biopsy inthe control group have expressed dif-ferences from that in the basic group.

The purpose of the laboratory bloodanalysis before and after treatment wasto study the metabolism of the connec-tive tissue in the process of anti-scarstherapy, 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

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PHYSIOLOGICAL REGULATING MEDIC INE 2011

tial diagnostic indicators of pathologi-cal process cicatrization activity.

We studied the free and boundoxyproline, total collagen, gly-cosaminoglycans (GAGs), vitamin C,flavin adenine dinucleotide, L-trypto-phan, core-protein in both groups ofpatients, 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 collagenmetabolism is the content of oxyprolinein the blood.

– Oxyproline (proline derivative) isone of the collagen basic amino acids;this allows to consider it as a marker,which reflects the catabolism of thisprotein. About 20% of the peptides,which contain oxyproline releasedfrom the collagen molecules, areexcreted with the urine.

Only 1% of urine oxyproline is in freeform; the remaining 99% are the pep-tides’ components. In case of violation of collagen synthe-

sis the amount of cross-links in collagenfibrils decreases, which leads to an in-creased content of easily soluble colla-gen. Therefore, in patients with impairedmetabolism of the connective tissue, theexcretion of oxyproline increases inurine, the content of its free fraction inthe blood increases, and the content ofits bound fraction decreases.

– GAGs play an important role in thetransport and exchange of water, salts,nutrients, and metabolites in tissues. The study of the structural and meta-bolic state of the connective tissuedemonstreted high activity of GAGs:the amount was largely increased in theblood plasma of patients in the 1st andin the 2nd group respectively (57,5 ±2,4 and 49,2 ± 1,3 micromole/l) afterour treatment, 1,5 and 1,2 times higher - respectively - than the indexes of thecomparison group (conventionallyhealthy patients).

– Collagenolytic activity (CLA) had sim-ilar dynamics and didn’t depend on thechoice of therapeutic method. The highest CLA values were recordedin patients with the standard therapymethod (46,8 ± 2,3 micromole of

oxyproline l/h). Levels of plasma CLAin 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 andprognostic value in determining predis-position to a pathological cicatrizationand, of course, to choose the method oftherapy.

The average of free oxyproline in bothgroups before the treatment was 2,170,65 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 wasa significant increase of bound oxypro-line in serum compared to the indica-tors of control individuals (27,3% and46,6%), respectively (d < 0,001). If we take into account that the level offree 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 oxyprolinemillimole/l

bind oxyprolinemole/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

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PHYSIOLOGICAL REGULATING MEDIC INE 2011

processes in the connective stroma ofthe organs (Kaminskaya G., PuryaevaN.L., 1990; Sodikova N.B, 2002), theindexes of the above mentioned mark-ers in the pathogenesis of the patholog-ical scars formation becomes clear.

The analysis of the research results ofthese parameters allows us to get tothe following conclusions: the for-mation of pathological scars is ac-companied by profound metabolicdisorders of the connective tissueand it is confirmed by a significantincrease of collagenolytic activity ofblood serum and glycosaminogly-cans content in it.

Evaluative studies of oxyproline showedthe most pronounced changes of bindoxyproline after the treatment, where-as the rates of free oxyproline were mul-tidirectional. Almost half of the patientsin the two groups showed an increaseof this index, which indicates an in-creased level of connective tissue re-modeling.

In other patients, against the back-ground of basic therapy, the freeoxyproline levels were low, which - onthe contrary - reflects the reduction inthe intensity of collagen metabolism,perhaps as a result of the therapy wecarried out. The GAGs index may be a predictivecriterion for the selection of the thera-peutic measures. The high correlationbetween the dynamics of collagenolyt-ic activity and the level of bind oxypro-line of blood plasma allow us to usethem as monitoring criteria for the ef-fectiveness of the conducted therapy.

Catabolism of the connective tissue iscarried out in the intercellular substanceunder the influence of specific en-zymes: collagenase, elastase, proteas-es, glycosidases.

Peptide chains of collagen are formedon polyribosomes, associated with themembranes of the endoplasmic reticu-lum (EPR). Simultaneously with thetranslation of DNA, hydroxylation of

proline and lysine residues takes placein peptide chains. Ascorbic acid acts as a reducing agent,which contributes to the hydroxylatediron in the ferrous state.

Hydroxylation of proline is necessaryfor the formation of a stable triple helixstructure of collagen. Hydroxylation oflysine is necessary for the formation ofcovalent bonds between molecules ofcollagen in the formation of collagenstructures. Hydroxylysine residues aresites of glycosylation. – In case of vitamin C deficiency, thecollagen synthesis breaks down at thestage of hydroxylation. Less strong andless stable collagen fibers emerge.

As a result of our investigation, we es-tablished that patients who were in thebasic treatment group had a signifi-cantly important increase in the level ofvitamin C during the therapy, more thanthe control group, and in both groupswithout 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 membraneand grows into the cavity of the EPR.

Here begins the synthesis of gly-cosaminoglycans and proteoglycanspart. As a result of our study of core-pro-tein before the treatment, we found outthat there is a qualitative positive reac-tion in the two studied groups (posi-tive/positive), whereas in the group ofconventionally healthy people, this re-action was negative (negative/negative).

On the background of our therapy inthe 1st group submitted to the basictreatment we saw reaction changes fornegative/positive.

In the 2nd group of patients reaction onthe core-protein remained unchanged(positive/positive).

Our data indicate the impact of thetreatment on the first reactions of gen-eration of the carbohydrate componentof proteoglycans, which occurs in theEPR. Most of the subsequent stages of gli-cosamin chains synthesis and theirmodifications 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 ofmonosaccharides and highly specificglycosyltransferase. To study their effectwe 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 aviolation of metabolism oxidative stageof connective tissue at the level ofFAD/FADH as mandatory participantsof 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 thetreatment, an oxidized form increase ofcoenzymes of flavin-dependent form. At a deeper study of bioenergeticprocesses in the cell, we analyzed theratio of FAD+ and FADH2, as regulatorsof the mitochondrial respiratory chain. In all the groups the reduction of FADH2

(0,0294±0.001 micromole/l) by the

0,450,4

0,350,3

0,250,2

0,150,1

0,050

Beforetreatment

Consideredas healthy

1st Group 2nd Group

Aftertreatment

Vitamin C levels in patients with pathological

scars, depending on the treatment method.

FIG. 1

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PHYSIOLOGICAL REGULATING MEDIC INE 2011

control values (0,054±0,005 micro-mole/l) was observed. The concentration of FAD+ (0,234±0,13micromole/l) in both groups was signifi-cantly higher (d <0,05) than in the groupof 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 thesedata before and after our treatment, wefound out that in the first group withthe basic treatment the rates of FAD+and FADH2 tended to improve, whilein the second group they remained atthe same level.All this may indicate a reduction of di-hydroxyacetone phosphate, an inter-mediate metabolite of glycolysis andgluconeogenesis, which leads to a ratereduction of gluconeogenesis and thestarting of the pentose phosphate path-way, and consequently, to an increasedformation of pathological scars in thesecond group of patients. The growth of FADH2 concentration, incomparison with FAD+, slows down theoxidation in the pentose-phosphatepathway, thereby the ratio oflactate/pyruvate is increasing, whichfurther reduces the rate of gluconeoge-nesis, and increases the lactate con-centration in blood. Oxidative decarboxylation of pyruvate isaccompanied by the formation of FADH2

and the kynurenic pathway and its endproducts are directly dependened on theconcentration of FAD+, which is involvedin the mitochondrial respiratory chainand provides the ATP cell.

It is known that the ratio of FAD+/FADH2

in the cell is a relatively stable rate andthat the reduction of FADH2 reduces thespeed of decarboxylation of pyruvate.Thus, the rate of change in the ratio ofFAD+/FADH2 is an important factor,which represents the energy needed bycells to regulate the rate of oxidation inthe mitochondria and being responsiblefor the mechanism of the pentose phos-phate pathway regulation.

Tryptophan is a source of nicotinamidecoenzyme forms (NAD+ and NADP) ofvitamin B5; the tryptophan metabolismis also associated with the formation ofbiogenic 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 influenceconsiderably the metabolism of variousorgans and tissues. – Analysis of scientific data shows thatthe studies of the tryptophan metabo-lism and pathogenic role of its meta-bolic products in the mechanisms ofpathological scarring developmenthave not found the proper reflection inthe scientific literature now available. This issue is of great scientific interestto study the pathogenic mechanisms ofpathological scars formation, diagnos-tic optimization of difficulty degree ofthe process of cicatrization and devel-opment of the appropriate treatment.

It is known that L-tryptophan is the sta-bilizer of the enzyme TDO (tryptophan-2, 3-dioxygenase). It contributes to the formation of a sta-ble conformational state, the TDO hasan absolute substrate specificity towardsthe L-tryptophan and catalyzes the irre-versible key reaction of amino acid ca-tabolism in kynurenic pathway of itsmetabolism with the formation of N-formyl-L-kynurenine, and later one ofthe key end-metabolites – NAD+. – This enzyme accelerates the incorpo-

Beforetreatment

Consideredas healthy

1st Group 2nd Group

Aftertreatment

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

Beforetreatment

Consideredas healthy

1st Group 2nd Group

Aftertreatment

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

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PHYSIOLOGICAL REGULATING MEDIC INE 2011

ration of molecular oxygen directlyinto the molecule of L-tryptophan andits catalyzed reaction is a factor whichlimites the speed of reaction of theconversion 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 groupsbefore the treatment (TAB. 4). In these metabolic conditions the way ofincreased synthesis of NAD+ and NADP+

coenzyme opens, needed to strengthenthe reducing syntheses of tissue differen-tiation and proliferation. The regulation of TDO is put into effectby the feedback of kynurenic pathway fi-nal products of L-tryptophan NAD+ andNADP+ metabolism, whereas the en-zyme activation is associated with an in-crease of the substrate oxidation contentL-tryptophan. Positive activators of the TDO enzyme areCu2+ ions, hematin, ferriheme and σ-aminolevulinic acid (σ-ALA). Hemin is aTDO. A significant increase in the TDOactivity allows to evaluate the reductionof the protein synthesis function of con-nective tissue in patients with pathologi-cal scarring, and particularly about thedisturbance 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 otherhand – the oxidized form of heme(hemin) inhibits the activity of the mito-chondrial enzyme σ-aminolevulinic,which catalyzes the first reaction of hemesynthesis from succinyl-CoA and glycine,σ- aminolevulinic acid.

The main suppliers of reduced substratesare the central metabolic pathways – ox-idative decarboxylation of pyruvic acidand citric acid cycle. Both of them are realized in the mito-chondria matrix.In the course of this processes reactionsof decarboxylation occur (the most partof all the carbon dioxide produced in thecells 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 therespiratory chain of the internal mito-chondria membrane, where its oxidationby oxygen to water and synthesis of ATPoccurs. 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 thetreatment, any statistically significantchanges in the dynamics of L-trypto-phan content in serum and the TDO en-zyme activity (d <0.05) were not foundout, although the stable dynamics in in-creasing of L-tryptophan and TDO.However, against the background of theconducted therapy the parameters of L-tryptophan and the enzyme TDO activ-ity differed significantly in the patientsof the 1st group: they were 55,12 ± 2,3micromole/l and 38,5 ± 2,1 nanomolekynurenine/mg of protein∙1 hour forthe L-tryptophan and enzyme TDO ac-tivity respectively, and in the 2nd group59,192 ± 2,5 micromole/l and 40,1 ±2,1 nanomole kynurenine/mg of protein1 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 regulationin the pathogenesis of pathologicalscarring formation. However, the eval-uation of metabolites of L-tryptophanmetabolism allows to make a predictiveconclusion about the level of activityor 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

Beforetreatment

Consideredas healthy

1st Group 2nd Group

Aftertreatment

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

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PHYSIOLOGICAL REGULATING MEDIC INE 2011

phan metabolism makes it possible toconfirm 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 serumand the TDO enzyme activity, which re-flects one of the important links in thestructural and metabolic disorders dur-ing the development of pathological ci-catrization.

The laboratory study of the indexes ofconnective tissue metabolism makes itpossible to optimize the pathogenetictherapy of pathological scars, namely:the inclusion of therapeutic and healthpromotion programs, which are aimedat normalization of the neuroendocrineregulation of L-tryptophan metabolism,organism detoxification, correction ofmetabolic acidosis, increasing the lev-el of antioxidant protection and inhibi-tion of oxidative stress, increasing of theimmunological resistance in conjunctionwith local impact. The efficiency controlof remedial measures can be realized bystudying the metabolites dynamics of theamino acid L-tryptophan metabolism,which has a great prognostic value of thecicatrization process result.

CONCLUSIONS

The results of ths study demonstrate thehigh clinical efficacy of the presentedmesotherapeutic treatment of patholog-ical scars compared to the traditionaltreatment, 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 earlystart of treatment.

4) Getting clinically more full-fledged re-sult when working with biologicallysafe medicines.

5) Determination of laboratory diagnosticindicators, which make it possible tocontrol 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 scarswith Made® and Guna®-Collagen canachieve significant functional and aes-thetic results in a shorter period oftreatment; it doesn’t have any compli-cations or negative side effect, nor anyspecial requirements for equipment isneeded. 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. �

author’s address

Dr. Svetlana Korkunda, PhD.– Docent in the Department of Com-

bustiology, Reconstructive, andPlastic Surgery of KhMAPE.Kharkiv City Hospital EmergencyMedical Care.

Kharkiv - Ukraine

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