130 Проблемы биологии и медицины, 2015, №1 (82)
УДК: 615.837.3-615.254.7-612.014.464
TREATING PATIENTS WITH UROLITHIASIS AFTER PERFOMING EXTRACORPOREAL
SHOCKWAVE LITHOTRIPSY COMBINED WITH OZONE THERAPY
V.V. VIZNIUK
Bukovinian State Medical University, Ukraine, Chernovtsy
СИЙДИК ТОШ КАСАЛЛИГИ БИЛАН ОҒРИГАН БЕМОРЛАРНИ ОЗОНОТЕРАПИЯ БИЛАН
ЭКСТРАКОРПОРАЛ ЗАРБА-ТУЛҚИНЛИ ЛИТОТРИПСИЯДАН СЎНГ ДАВОЛАШ
В.В. ВИЗНЮК
Буковина Давлат тиббиёт университети, Украина, Черновци
ЛЕЧЕНИЕ БОЛЬНЫХ С МОЧЕКАМЕННОЙ БОЛЕЗНЬЮ ПОСЛЕ
ЭКСТРАКОРПОРАЛЬНОЙ УДАРНО-ВОЛНОВОЙ ЛИТОТРИПСИИ В СОЧЕТАНИИ С
ОЗОНОТЕРАПИЕЙ
В.В. ВИЗНЮК
Буковинский Государственный медицинский университет, Украина, г. Черновцы
35 нафар уролитиаз билан хасталанганларга экстрокорпорал тулкинли литотрипсия утказилган-
дан кейин 10 кун давомида ички озонотерапия утказилиб, калькулез пиелонефрит касаллигининг ке-
чишига таъсири курилди. Унинг кулланишидан ижобий таъсир конда липидларнинг перекисли окси-
дланиш махсулотларнинг камайиши, антиоксидант фаоллигининг купайиши оркали исботланди.
Калит сўзлар:
калькулез пиелонефрит, экстрокорпорал зарба-тўлқинли литотрипсия, перекис-
ли оксидланиш липидлари, антиоксидант химоя ферментлари, озонотерапия.
35 человек с уролитиазом были вовлечены в исследования для того, чтобы узнать, как в течение
10 дней внутривенная озонотерапия влияет на ход течения с калькулезным пиелонефритом после
проведенного экстракорпоральной ударно-волновой литотрипсии. Было установлено, положитель-
ный лечебный эффект вызванный его применением, которая была доказана путем уменьшения про-
дуктов перекисного окисления липидов в крови, и по увеличению антиоксидантной активности.
Ключевые слова:
калькулезный пиелонефрит, экстракорпоральная ударно-волновая литотрип-
сия, липиды перекисного окисления, ферменты антиоксидантной защиты, озонотерапия.
Introduction.
Urolithiasis is one of the most
common urologic diseases and, according to many
researchers, is one of the urgent problems of modern
urology [1]. This is caused both by its prevalence
and features of its etiology, pathogenesis, diagnos-
ing and of therapeutic approach to this disease. The
development of urolithiasisis caused by excretory
renal dysfunction at the stage of tubular reabsorp-
tion and secretion [1,3].
Invention of extracorporeal shock wave litho-
tripsy (ESWL) and its introduction into clinical
practice allowed us to increase the quality and effec-
tiveness of the treatment of various clinical forms of
urolithiasis [2, 9].
Special attention is paid to finding effective and
reasonably priced methods of the treatment. The
ozone therapy has been widely used recently for the
same reason [5, 8]. Methods of combined local and
intravenous ozone therapy, together with active sur-
gical tactics, contributed to the improvement of the
general condition of patients, to reducing indices of
endotoxemia, early elimination of microorganisms,
acceleration of regenerative processes as well as to
the reduction in the duration of hospital treatment
[4,6,9].
Material and methods
. The effect of ozonated
solutions on biochemical indices of blood, system of
lipidperoxidation (LPO) andantioxidant defence
(AOD) were investigated in 35 patients, suffering
from
urolithiasis
with
chronic
calculous
pyelonephritis while treating them by means of
ESWL method.
Ozone was obtained, using an automated ozone
plant “Bozon” produced by NPP “Econica” in
Odessa. The technological process of production of
ozone containing saline was conducted by following
a standard technique of preparing ozone containing
saline for parenteral injection according to methodi-
cal recommendations of Health Ministry of Ukraine
in 2004. A standard set for ulnar artery catheteriza-
tion was used for intravenous infusion.
For the procedure, sterile saline in an amount of
200-400 ml was poured into a quartz vessel of the
plant "Bozon", set in the mode of desired concentra-
tion of ozone in saline (1-5 mg / l), waited for the
procedure of the preparation of ozone in required
concentration in saline to be over, then it was inject-
ed intravenously to patients at a speed of 80-100
drops per minute [2, 5, 10] for 10 days.
V.V. Vizniuk
Биология ва тиббиёт муаммолари, 2015, №1 (82) 131
Investigation of biochemical blood parameters,
system activity of lipid peroxidation and antioxidant
defense were conducted in 30 patients suffering
from urolithiasis with calculous pyelonephritis in
the preoperative period, on the 3
rd
-4 th day and 9
th
-
10
th
day after the session of extracorporeal shock-
wave lithotripsy. ESWL was performed by means of
the apparatus Magna Duet of Direx firm, after fluor-
oscopic directing the working part on the concre-
ment. Beginning with the minimum amplitude and
force of impact, lithotripsy session started. Gradual-
ly the strength and frequency of shocks were in-
creased to 6 HV and 120 beats / min, respectively.
Lithotripsy session lasted up to 3000 bpm.
The condition of blood biochemical parameters,
lipid peroxidation, antioxidant defense in 30 patients
with urolithiasis against the background of calculous
pyelonephritis treated in the urological department
of «Emergency Hospital" Chernivtsi were studied.
Comparison group consisted of 20 relatively healthy
blood donors and those who were on the examina-
tion in urological department.
Oxidation of lipids was evaluated in terms of:
content of primary productsin blood- conjugated
dienes (CD) in units of optical density of lipids
(considering methodical recommendations of V.B.
Havrylova and M.I. Myshkorudna, 1983), as well as
in terms of contents of secondary reactive com-
pounds in the plasma, such as malonic aldehyde
(MA) in mcm/l of blood (Staleva, 1977), of choles-
terol, triglycerides and lipids (V.V. Menshikov,
1965)
.
As to the antioxidant enzymes, they were tested
for vitamin E (α-tocopherol) in mm / l in the serum
(R.S. Kysylevych, 1972); ceruloplasmin activity in
the serum (E.V. Ten, 1981); catalase activity in the
blood ME -103 (M.A Koroliuk and co-authors,
1988); peroxidase activity in the blood, s.u / liter
.
(for 1 s.u. of the activity is accepted the change of
the optical density of the reaction medium at 520
nm over 0.001 per h at 37 ° C); glutathione peroxi-
dase activity in blood glutathione mm / min l (B.P
Pleshkov, 1976); glutathione reductase activity in
blood oxidized glutathione m / l min (M.I Ridkyi,
1997), as well as general antioxidant activity using
M.P Grigorieva’s technique (1984).
Statistical analysis of the data was performed
on modern PC IBM by analysis of variations, de-
termining Student's criteria using the standard appli-
cation package STATISTICA "Statgraficsplus 7.0"
and "BioStat" [7].
Results and discussion.
Effect of ozonated solutions on biochemical in-
dices of blood lipid peroxidation system and AOD
in patients with urolithiasis with chronic calculous
pyelonephritis while using ESWL method showed
that dynamic of changes of urea content in the blood
is markedly different from that of the comparison
group patients. Thus, in the group ESWL + O3 the
level of urea increased from 6,34 ± 0,048 mg / l to
6,82 ± 0,05 mmol / l, which was 7.5% compared
with a group of healthy individuals), and in the
comparison group, the figure was 20.6%. Thus the
difference in the increase was 13.1%. The big dif-
ference between the rates was noted in the analysis
of creatinine in the blood (44%). Obviously, for this
reason, in patients treated with ozone therapy, there
were no significant deviations of creatinine clear-
ance. Thus, the filtration capacity of the kidneys is
not impaired (Table. 1).
It should be noted that creatinine content in the
blood nine days after ESWL + O3 was lower than
before the operation, closer to that of the group of
healthy individuals.
Content of lipids in plasma in patients of this
group increased slightly in the postoperative period
on the background of ozone therapy. Without a use
of ozonated solutions on the 3
rd
-4
th
day after ESWL
the content of total lipids in plasma as well as cho-
lesterol and triglyceride rates increased by 12.6%,
19.2%, and 38.8%, respectively, while after applica-
tion of ozone therapy these figures only increased
by 1.4%, 8.6% and 5% respectively. Atherogenic
index did not increase so sharply.
Тable 1
Indices of LPO products and renal function after ESWL + ozone therapy performing
Indices
Units
Raw da-
ta(n=35)
3
rd
-4
th
day after
ESWL
Р
9
th
-10
th
day after
ESWL
Р
Clearance.
ml/min.
102,3±0,87
99,5±1,2
>0,05
98, 1±0,75
>0,05
Lipids gen..
g/l
5,64±0,12
5,72±0,14
>0,05
5,2±0Д
<0,05
triglycerides
mm/l
1,19±0,07
1,25±0,05
<0,05
1,15±0,08
<0,05
Plasma DC
Un.opt.Deщ.
0,308±0,03
0,349±0,021
<0,05
0,305±0,03
<0,05
МА
Мcmol/l
0.785±0,0128
0.960±0,015
<0,05
0.891±0.013
<0,05
Urea
mmol/l
6,34±0,048
6,82±0,05
<0,05
6,7±0,04
<0,05
creatinine
mmol/l
0,085±0,004
0,198±0,004
<0,05
0,10210,005
<0,05
Atherogenic
index
2,34±0,12
2,59±0,04
<0,05
2,18±0,09
<0,05
Note: The validity of the results at P <0.05
Treating patients with urolithiasis after perfoming extracorporeal shockwave lithotripsy ...
132 Проблемы биологии и медицины, 2015, №1 (82)
Table2
Values of carbohydrate metabolism after ESWL+ ozone therapy
Values
Units
Raw data
(n=35)
3rd and 4th days after
ESWL
Р
9
th
and 10
th
days after
ESWL
Р
Blood glu-
cose
mM/l 4,81 ±0,15
4,02±0,2
<0,05
4,7±0,16
<0,05
Lactate
mM/l 1,02±0,017
0,85±0,01
<0,05
0,89±0,012
<0,05
Pyruvate
mM/l 0,08±0,004
0,06±0,003
<0,05
0,074±0,005
<0,05
L/Pyruvate
mM/l 12,75±1,02
14,16±0,8
>0,05
12,0210,65
<0,05
Note: The validity of the results at Р< 0,05
In the application of ozone therapy it increased
2,59 ± 0,04, whereas patients in the comparison
group, it increased to 3,8 ± 0,1, i.e the difference
was 46%. These data support the view that the high
content of oxygen in the blood due to introduced
ozone improves lipid oxidation, prevents the trans-
formation of suboxide products of fats into choles-
terol. The favorable tendency of increased utiliza-
tion of blood lipids in patients suffering from uro-
lithiasis with chronic calculous pyelonephritis in
parenteral injections of ozone solutions is also ob-
served in more distant periods of observation.
Pronounced effect of ozonized solutions in the
course of urolithiasis with chronic calculous pyelo-
nephritis after ESWL is observed at the level of car-
bohydrate metabolism: lactate and pyruvate. Thus,
the concentration of lactate decreased from 1,02 ±
0,017 mmole / l to 0,85 ± 0,001 mmole / l on the 3
rd
-
4
th
day after a session of ESWL, representing 32.8%
of the indicators of healthy individuals. At the same
time, in patients in the comparison group, the figure
was 17.0%. During the next days after the ESWL
there was an increase in lactate (Table. 2).
On the 3
rd
-4 th day after ESWL pyruvate rate
decreased by 25% from the baseline (from 0,08 ±
0,004 mg / l to 0,06 ± 0,006 mmol / l). On the 3
rd
,
4
th
, and 9
th
, 10
th
postoperative day the pyruvate rate
remained below the original one. Ratio lactate / py-
ruvate for the entire observation period remained at
the level of the control parameters. The concentra-
tion of glucose oxidation products decreased and
remained lower than in the preoperative period. This
tendency showed a significant effect of ozone on the
div's energy processes in examined patients, suf-
fering from urolithiasis with chronic pyelonephritis.
It can be assumed that increasing the amount of ox-
ygen in the blood normalizes the ratio both of aero-
bic and anaerobic ways of glucose oxidation, there-
by stimulating more efficient process of energy pro-
duction. Activation of oxygen dependent ways was
accompanied by increased glucose utilization. On
the 3
rd
-4
th
day after ESWL glucose rate decreased
from 4,81 ± 0,15 mmol / l to 4,02 ± 0,2 mmol / l and
was 16% from the basal value.
The level of serum ceruloplasmin in patients
with urolithiasis with chronic pyelonephritis after
ESWL and ozone therapy dramatically increased
from 0,31 ± 0,05 units of opt. dens. to 0,61 ± 0,031
un. of opt. dens., representing 49% of the basal val-
ue, while the concentration of uric acid remained
mostly the same.
The level of concentration of α-tocopherol in
patients with urolithiasis with the treatment using
ESWL and ozone therapy on the 3rd -4
th
day was
9.9% from the baseline. On the 9
th
day after ESWL
the level of α-tocopherol concentration increased by
22% from the basal value. However, in the compari-
son group there was a reduction of α-tocopherol by
11% on the 3
rd
-4
th
days and 13% - on the 9th day of
post-operative course.
It is obviously that less intense process of α-
tocopherol formation and reduction in its concentra-
tion in patients of the comparison group was a result
of its more intensive use in the reaction of "catch-
ing" free radicals, while the use of ozonated solu-
tions stimulates the synthesis of α-tocopherol.
It can be assumed that the activation of aerobic
ways of energy production contributed to the bio-
synthetic functions, such as accelerated biosynthesis
of proteins and enzymes, including ceruloplasmin
enzyme.
An important effect of ozone therapy in patients
with urolithiasis on the processes of free radical ox-
idation of lipids and on enzymatic activity of antiox-
idant protection system occurs with excessive
ozone, which significantly weakens the formation of
conjugated dienesand malonic aldehyde. Thus, if we
compare, without using ozone in the control group,
on the 3rd -4th day after ESWL, the concentration
of CD and MA increased by 51,2% and 68%, re-
spectively.
In the group of patients who used ozone therapy
at the same time the concentration of both primary
(CD) and secondary products (MA) of lipid peroxi-
dation in the blood increased only by 13.3% and
22.2% respectively.
9-10 days later after ESWL and ozone therapy
the level of lipid peroxidation products decreased in
patients with urolithiasis, approaching to that of the
preoperative period.
V.V. Vizniuk
Биология ва тиббиёт муаммолари, 2015, №1 (82) 133
Table 3
Indices of antioxidant enzymes after extracorporeal shock wave lithotripsy combined with ozone therapy
Indices
Units
Raw data
(n=35)
3rd -4th day after ESWL
Р 9
th
-10
th
day after ESWL
Р
Catalase
МЕх10
3
19,44±1,35
22,06±1,19
<0,05
24,61±1,1
<0,05
Peroxidase
s.u./l
127,3±4,36
152,4±5,48
<0,05
149,5±4,91
<0,05
Gl.peroxidase
МЕх10
3
19,44±1,32
24,71 ±2,3
<0,05
23,14±2,1
<0,05
Gl.reductase
ME
585,1±46,3
671,9±34,21
<0,05
708,3±24,9
<0,05
α-tocopherol
mg/%
1,92±0,02
2,11±0,015
<0,05
2,34±0,01
<0,05
uric acid
mm/l
232,6±26,4
285,9±29,6
<0,05
315±34,7
<0,05
Ceruloplasmin
Un.ofopt.dens. 0,31±0,05
0,61 ±0,031
<0,05
0,49±0,04
<0,05
Note: The validity of the results at Р< 0,05
Table 4.
Indices of blood and urine lactate dehydrogenase isozyme spectrum after ESWL +ozone therapy
Indices
Units
Raw data(n=35) 3
rd
-4
th
day after ESWL
Р
9
th
-10
th
day after ESWL
Р
Gen.bl.LDG
mcM(ls)
1,6±0,013
1,7±0,03
<0,05
1,56±0,012
>0,05
LDG1
mcM(ls)
0,509±0,0062
0,598±0,0054
<0,05
0,515±0,006
<0,05
LDG2
mcM(ls)
0,69 1 ±0,003
0,698±0,0029
<0,05
0,675±0,0025
0,05
LDG3
mcM(ls)
0,259±0,002
0,269±0,0012
<0,05
0,246±0,0018
>0,05
LDG4
mcM(ls)
0,093±0,008
0,088±0,006
<0,05
0,087±0,006
<0,05
LDG5
mcM(ls)
0,048±0,001
0,042±0,0012
>0,05
0,055±0,0015
>0,05
Gen.ur.LDG
mcM(ls)
0,196±0,067
0,294±0,05
<0,05
0,275±0,041
<0,05
LDG1
mcM(ls)
0,07 1 ±0,015
0,121 ±0,004
<0,05
0,117±0,035
<0,05
LDG2
mcM(ls)
0,058±0,015
0,076±0,01
<0,05
0,081 ±0,02
<0,05
LDG3
mcM(ls)
0,036±0,0014
0,044±0,001
<0,05
0,034±0,001
<0,05
LDG4
mcM(ls)
0,015±0,001
0,021 ±0,002
<0,05
0,018±0,001
<0,05
LDG5
mcM(ls)
0,017±0,003
0,032±0,007
<0,05
0,025±0,005
<0,05
Note: The validity of the results at Р<0,05
A significant weakening of free radical oxida-
tion of lipids was the result of the activation of en-
zymatic antioxidant defense system. Activation of
defense mechanisms under the influence of ozone
therapy occurred with less intensity compared with
the processes of lipid peroxidation, and it is seen
well judging by the catalase activity rate. On the 3rd
- 4th day its activity was 22,06 ± 1,19 Meh103 from
the baseline. Only nine days after ESWL its activity
does not differ at all from that of the comparison
group of individuals (24,61 ± 1,1 Meh103).
The activity of the enzyme glutathione peroxi-
dase and glutathione reductase in the early postoper-
ative period, i.eon the 3rd -4th day, in patients of the
comparison group tended to a sharp decline and re-
mained at a lower level than at the preoperative
stage. At the same time, the activity of glutathione
reductase and glutathione peroxidase after ozone
therapy tended to increase by 15% and 27% on the
3rd -4th day, and further the activity indices re-
mained at a consistently high level.
The enzyme activity of peroxidase increased.
After 3-4 days and on the 9th-10th days its activity
was higher in patients who had undergone ozone
therapy and accounted for 19.6% of the initial level.
The atomic oxygen (ozone decay product) may be a
specific inducer, under whose influence the synthe-
sis of this enzyme in tissues takes place (Table. 3).
Changes in the activity of the blood LDG, in
general, resembled the development of changes in
the comparison group of people, who hadn’t used
the ozone therapy. Indices of LDHKR activity 10
days after ESWL did not differ from that of the ac-
tivity of healthy individuals. In LDG isozyme spec-
trum of blood LDG 1,2,4 fractions prevailed in 3-4
days after ESWL. However, after 10 days of post-
operative course there was a slight increase in ac-
tivity of fractions LDG4 and LDH5 which indirectly
points to an increasing permeability of parenchyma-
tous organs cellular membranes.
More significant differences in the activity of
LDG isozyme spectrum were noted in the urine.
This is due to the fact that extracorporeal lithotripsy
dramatically increases the activity of fractions
LDGD and LDG5. Parenteral application of ozo-
nized solutions in the preoperative and postoperative
Treating patients with urolithiasis after perfoming extracorporeal shockwave lithotripsy ...
134 Проблемы биологии и медицины, 2015, №1 (82)
period significantly alters the intensity of the activi-
ty and the distribution of LDG isoenzymes of urine.
3-4 days after ESWL there was a higher activity
of LDG fractions in the urine :from 0,071 ± 0,015
mmol
/ s
to 0,121 ± 0,004 mmol /
s
(70%), LDG3
from 0,036 ± 0,001 mmol /
s
to 0,044 ± 0,001 mmol
/
s
(22%) and LDG5 from 0,017 ± 0,003 mmol /
s
to
0,032 ± 0,007 mmol /
s
(88.2%).
These results suggest that extracorporeal litho-
tripsy affects the renal parenchyma and, in particu-
lar, the nephrocytebiomembranes. Using ozonated
solutions in pre- and postoperative periods reduces
the destructive processes significantly.
Thus, our studies of the impact of ozone on
post-operative condition of parenchymal organs –
the kidneys, the liver and the most important blood
parameters exhibit significant prospects of the
treatment in urology we had chosen.
Unlike the previous series of studies (comparison
group), LDG activity of the urine on the 3
rd
- 4
th
days grew slightly under the influence of ESWL +
ozone therapy (1.5 times). Subsequently, the activity
of the urine LDG reduced to the preoperative level
faster (Table. 4).
Thus, the use of ozonized solutions pro-
motes energy supply, reduces primary pathogenetic
link in cell membranes damage - lipid peroxidation
and improves the use of lipids in energy processes,
reduces cholesterol atherogenity, stabilizes process-
es of aerobic and anaerobic ways of glucose oxida-
tion, stimulates enzyme activity and non-enzymatic
components of the antioxidant defense of the div.
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David A. Tolley Urolothiasis : update on stone
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Extracorporeal shock wave lithotripsy for distal
ureteral calculi: what a powerful machine can
achieve / W.W. Hochreiter, H. Danuser, M. Perrig,
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Shockwave lithotripsy: dose-related effects on renal
structure, hemodynamics, and tubular function. /
L.R. Willis, A.P. Evan, B.A.Connors, [et al.] // En-
dourol. – 2005. – Vol. 19. – P. 90.
TREATING PATIENTS WITH
UROLITHIASIS AFTER PERFOMING
EXTRACORPOREAL SHOCKWAVE
LITHOTRIPSY COMBINED WITH OZONE
THERAPY
V.V. VIZNIUK
Bukovinian State Medical University, Ukraine,
Chernovtsy
35 people with urolithias is were involved in
the study in order to find out how the intravenous
ozone therapy, performed during 10 days, influ-
enced the course of the disease with calculous
pyelonephritis after conducted extracorporeal shock
wave lithotripsy. It was established a positive cura-
tive effect caused by its application which was
proved by a reduction of lipid peroxidation products
in the blood, by an increase of antioxidant activity.
Key words:
calculous pyelonephritis, extra-
corporeal shock wave lithotripsy, lipid peroxidation,
enzymes of antioxidant defense, lactate, ozone ther-
apy.
