Volume 03 Issue 11-2023
65
International Journal of Medical Sciences And Clinical Research
(ISSN
–
2771-2265)
VOLUME
03
ISSUE
11
P
AGES
:
65-88
SJIF
I
MPACT
FACTOR
(2021:
5.
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(2022:
5.
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)
(2023:
6.
184
)
OCLC
–
1121105677
Publisher:
Oscar Publishing Services
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ABSTRACT
The aim of the study was to learn of the effect of the new drug "Reomannisol" on wound healing, taking into account
pathomorphological aspects in the complex treatment of experimental diabetic foot syndrome.
Material and methods.
An experimental study was carried out on 140 outbred male rats weighing 220-250 g, kept in
the TMA vivarium. The experimental animals were divided into 4 groups: the 1st group was intact; 2nd group
–
the
creation of an experimental model of alloxan diabetes mellitus; 3rd control group - against the background of alloxan
diabetes, the creation of an experimental model of a diabetic foot using traditional complex treatment; 4th
experimental group - on an experimental model of diabetic foot - traditional treatment and reomannisol. On the skin
of each rat’s right hind paw’s footpad, a full
-thickness rectangular wound measuring 2 mm×5 mm was created with a
scalpel. Every day, the wounds were treated with the traditional method of treatment (5% alcohol solution of iodine
and levomekol ointment) until the end of the experiment, for the experimental group, the local traditional method of
treatment and intraperitoneal administration of the new Reomannisol preparation were used 1 time per day at a dose
of 1 ml of Reomannisol per 100 g of animal div weight for 5 days.
Results.
By the 10th day in the experimental group, an independent almost complete closure of the wound defect and
hair growth around the wound was noted. In the control group, on the 10th day, a wound defect of about 4.9 ± 0.05
mm2 remained, the wound healed on the 14th day of the experiment.
Research Article
IMPACT OF THE DRUG REOMANNISOL IN THE MODEL OF AN
EXPERIMENTAL DIABETIC FOOT
Submission Date:
November 12, 2023,
Accepted Date:
November 17, 2023,
Published Date:
November 22, 2023
Crossref doi:
https://doi.org/10.37547/ijmscr/Volume03Issue11-08
Ernazarov Khojimurod Irsaliyevich
Phd, General Surgery Department No.2, Tashkent Medical Academy, Uzbekistan
Journal
Website:
https://theusajournals.
com/index.php/ijmscr
Copyright:
Original
content from this work
may be used under the
terms of the creative
commons
attributes
4.0 licence.
Volume 03 Issue 11-2023
66
International Journal of Medical Sciences And Clinical Research
(ISSN
–
2771-2265)
VOLUME
03
ISSUE
11
P
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:
65-88
SJIF
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MPACT
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(2021:
5.
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(2023:
6.
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OCLC
–
1121105677
Publisher:
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Conclusion:
The use of local treatment and reomannisol can enhance angiogenesis in the early stages of the
experiment and restore disturbed microcirculation, increase macrophage response, fibroblast proliferation,
maturation and remodeling of granulation tissue and its epithelization, reduce the inflammatory reaction, which leads
to more effective and early healing of the wound area.
KEYWORDS
Experimental model of diabetic foot, experimental animals, diabetes mellitus, alloxan, surgical debridement,
reomannisol.
INTRODUCTION
Currently, one of the leading places in terms of growth
rates of morbidity, disability, and mortality was
occupied by diabetes mellitus (DM) among the so-
called "diseases of civilization" [3]. Today, over 460
million people are suffering globally from diabetes;
according to the predicted facts announced by the
International Diabetes Federation, by 2040 the number
of patients will increase up to 642 million [11].
Diabetes mellitus is accompanied by the development
of complications, including diabetic foot syndrome
(DFS), one of the leading clinical symptoms of which is
the persistence of an ulcer on the skin of the lower
extremities [14].
Delayed wound healing is one of the complications of
the disease due to multiple factors including poor
circulation [13], prolonged inflammation, and
hyperglycemia. It is a common cause of morbidity and
mortality in patients with DM [18]. When the wound
becomes chronic, it is prone to developing foot ulcers,
including neuropathy and foot deformities [13]. Foot
ulcers in DM are the cause of more than 50% of all non-
traumatic leg amputations [22]. Evidence has shown
that hyperglycemia is one of the main factors
contributing to slow wound healing [18] by increasing
cell apoptosis and decreasing cell survival in diabetic
wounds. It has been shown to inhibit endothelial cell
and fibroblast proliferation in humans [23], up to 75%
slower in adult mice with DM compared to control mice
[19].
At the present stage in experimental diabetology, the
most widespread chemical model of diabetes mellitus
uses substances that destroy β
-cells of the islets of
Langerhans [12, 15]. This study describes a model of
diabetes mellitus in rats, induced by the introduction of
a reduced dose of alloxan, which significantly reduces
the number of animal deaths.
The alloxan model of diabetes mellitus is one of the
most widespread and studied. It is actively used by
Volume 03 Issue 11-2023
67
International Journal of Medical Sciences And Clinical Research
(ISSN
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VOLUME
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researchers around the world. Alloxan is a structural
analog of glucose, due to which it accumulates in
pancreatic β
-cells and leads to their death, followed by
the development of diabetes. At the same time,
damage to β
-cells is accompanied by degenerative
changes in the kidneys and liver, which leads to high
mortality in laboratory animals on the first day after
alloxan administration. The problem of violations of
several types of metabolism with the introduction of
alloxan, the prevalence of manifestations of oxidative
stress as a typical pathological process in case of
damage to the key organ involved in all types of
metabolic processes (liver) dictate the need to
prescribe pathogenetic drugs from the group of
metabolic correctors with hepatoprotective and
antioxidant orientation. One of the promising new
drugs in this area is Rheomannisol (LLC "REKA-MED
FARM" Republic of Uzbekistan) - a complex drug with
antihypoxic, antioxidant, rheological, anti-shock,
detoxifying,
diuretic
action.
The
main
pharmacologically active substances are sodium
succinate and mannitol.
Aim of the study. Study of the effect of the new drug
"Rheomannisol" on endogenous intoxication and
wound healing, taking morphological aspects into the
complex treatment of experimental diabetic foot
syndrome.
Materials and research methods. The work was done
on experimental material. Healthy rats were selected
for the experiment. Experimental studies were carried
out on 140 outbred male rats weighing 220-250 g, kept
in the Tashkent Medical Academy (TMA) vivarium. The
rats were kept under optimal conditions, all rats lived
in a room with a 12-hour light-dark cycle and a constant
temperature of 22-25°C, with free access to water. All
rats were given a sufficient amount of a normal rodent
diet ad libitum. (diet for rodents, State standard No.
GOST R50258
–
92) and tap water daily. Operations and
all manipulations with animals were carried out using
general anesthesia, in compliance with the principles
of humanity outlined in the directives of the European
Community (86/609/EEC) and the Declaration of
Helsinki, by the "Rules for working with experimental
animals". The experimental animals were divided into
4 groups: the 1st group was intact; 2nd group
–
the
creation of an experimental model of alloxan diabetes
mellitus; 3rd control group - against the background of
alloxan diabetes, the creation of an experimental
model of a diabetic foot using traditional complex
treatment; 4th experimental group - on an
experimental model of diabetic foot - traditional
treatment and reomannisol.
After a 24-hour fast, the rats were weighed. A 2%
solution of alloxan diluted in 0.9% saline was
administered intraperitoneally as a single dose,
corresponding to a dose of 20, 15, 12 mg of alloxan per
100 g of animal weight. Food and water were given to
animals only 30 minutes after drug administration. On
Volume 03 Issue 11-2023
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International Journal of Medical Sciences And Clinical Research
(ISSN
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VOLUME
03
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65-88
SJIF
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(2021:
5.
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(2022:
5.
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)
(2023:
6.
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)
OCLC
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1121105677
Publisher:
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the 3rd day, the level of glucose in the blood was
assessed.
Determination of glucose concentration in the
peripheral blood of animals. Diabetes was confirmed 3
days after the blood glucose concentration was
determined. Peripheral blood glucose concentration
was measured with an “Accu Chek Active” glucometer
(Roche
Diagnostics,
Germany),
the
linear
measurement range was 0.6
–
33.3 mmol/L. Blood
sampling to study the level of glycemia was performed
from an incision in the tip of the tail. An experimental
model of diabetes mellitus (type I diabetes) has been
obtained. The day of verification of diabetes mellitus
was considered the zero-day of its development.
Surgical procedure. On the day of verification, the skin
surface of the right footpad was shaved and cleaned
with a 70% ethanol wipe. On the skin of each rat’s right
hind paw’s footpad, a full
-thickness rectangular wound
measuring 2 mm × 5 mm was created with a scalpel
[14]. The scalpel and scissor wounds (Day 0) were of
similar size and shape with minimal or no bleeding in all
groups. Every day, the wounds were treated with the
traditional method of treatment (5% alcohol solution of
iodine and levomekol ointment), until the end of the
experiment, also for the experimental group, in
addition to the local traditional method of treatment,
a new drug Reomannisol (JV LLC REKA-MED FARM,
Republic of Uzbekistan) was used, which was
administered intraperitoneally once a day for 5 days, in
single doses of the therapeutic range for humans,
taking into account differences in relative div surface
area [1]. In all cases, the average dose of the studied
range was 1 ml of Reomannisol per 100 g of the
calculated equivalent mean therapeutic dose (EMTD).
The development of the disease was assessed by the
condition of the animals, lethality was recorded in
groups, and recorded according to clinical symptoms
(polyuria, polydipsia, polyphagia, weight loss, coat)
and blood glucose levels. The wool of animals normally
has a peculiar luster and is usually adjacent to the skin.
The amount of water drunk by the rats was determined
individually by measuring its volume with a measuring
cylinder before and after the animals took water. To
assess the daily values of diuresis, an individual urine
collection was performed using urinals.
Rats were taken out of the experiment by decapitation
on days 1, 3, 7, 10, 14, blood was taken for laboratory
examinations: biochemical analyzes (total protein,
ALT, AST, glucose, creatinine, urea), products of lipid
peroxidation (LPO) (malondialdehyde - MDA),
indicators endogenous intoxication (MWM, SCE),
morphological studies of tissues taken from the wound
zone and the surrounding intact area were carried out.
At each time, sampling for analysis was carried out in
10 animals of each group.
Biochemical analyzes (the activity of aspartate
aminotransferase (AST), alanine aminotransferase
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(ALT), total protein, glucose, creatinine, urea) were
measured on a biochemical analyzer photometer
Mindray BA-88A (Mindray, China), using a set of
chemical
reagents
manufactured
by
Human
(Germany).
Determination of malondialdehyde (MDA) using
thiobarbituric acid. At high temperatures in an acidic
medium, MDA reacts with 2-thiobarbituric acid,
forming a colored trimethylene complex, with an
absorption maximum at 532 nm on an SF-46
spectrophotometer (Russia). The molar coefficient
was used - 1.56x105cm-1 x M-1. The MDA level was
expressed in µmol/L [9].
A biochemical method for determining endogenous
intoxication, which consists in choosing the level of
medium-weight molecules in the blood serum. Medium
weight molecules (MWM) are an integral biochemical
marker of endogenous intoxication (EI). In the blood
plasma of all subjects, the level of MWM was assessed.
For this, a screening method for determining
molecules was used, this method includes taking
blood, separating serum from blood cells by
centrifugation, obtaining a protein-free sample by
adding 0.5 ml of 10% trichloroacetic acid to 1 ml of blood
serum, and centrifuging for 30 minutes at 3000 rpm in
min. Next, 4.5 ml of distilled water is added to 0.5 ml of
the supernatant and the optical density of the sample
is determined on a spectrophotometer with a wave
characteristic of 254 nm. The content of molecules of
average mass is determined by the size of the optical
sample, and the presence of endogenous intoxication
is judged by their high degree. Measurement of the
level of MWM and oligopeptides allows you to
calculate the Integral index of intoxication. To
calculate the optical density in the ultraviolet region of
the spectrum, a UNICO 2800 spectrophotometer
(USA) was used [2].
Determination of the concentration of oligopeptides
(OP). The method for determining the content of OP
according to Lowry (1956) was used. To do this, 1 ml of
a weakly acidic supernatant diluted 10 times with
distilled water was taken, 2 ml of an alkali-copper
reagent was added, and left for 10 min. at room
temperature, then 0.2 ml of the Folin-CiocALTeu
reagent was added, stirred, and after 30-40 minutes.
the optical density was measured at 750 nm in a cell
with a length of 5 mm on a UNICO 2800
spectrophotometer (USA) [20].
The sorption capacity of erythrocytes (SCE) was
determined by a method based on the idea of an
erythrocyte as a universal adsorbent [10]. To do this, 1
ml of erythrocyte suspension was transferred into a
test tube with 3 ml of 0.025% methylene blue in
physiological saline. After a 10-minute incubation at
room temperature, the sample was centrifuged for 10
minutes. at 3,000 rpm the optical density of the
supernatant and the initial solution of methylene blue
was determined concerning physiological saline at a
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wavelength of 630 nm using a UNICO 2800
spectrophotometer (USA). The amount of absorbed
dye was expressed as a percentage [10].
Evaluation of the effectiveness of the drug was carried
out based on, also, a visual examination of the animals
and their wounds. The criteria for the effectiveness of
the drug for the wound were: focusing on the severity
and duration of inflammatory manifestations in the
wound area (edema, hyperemia, wound exudate), the
state of the wound bottom; the appearance of
granulation tissue; reduction in the area of the wound
defect; the appearance of marginal epithelialization;
acceleration of wound healing,
The L.N. Popov test was used to determine the area of
the wound. A sterile cellophane plate is placed on the
wound and the contour of the wound is applied to it.
The drawing is transferred to graph paper and the area
of the wound is calculated.
Where ΔS
is the desired value in cm2;
S is the area of the wound in the previous
measurement in cm2;
Sn - the size of the area of the wound at the moment in
cm2;
t is the number of days between measurements [5].
The research methods described in the classical
manuals on histomorphology were applied in the work
[18]. Pieces from a diabetic foot, pancreas, and liver
were fixed in Carnoy's solution (the composition of the
fixative was glacial acetic acid, 10 parts; chloroform, 30
parts; ethyl alcohol, 60 parts). Fixing the pieces for 2-4
hours, then placing the pieces in 96% alcohol. Carrying
out the wiring in the usual way and pouring in paraffin.
Making histological sections with a thickness of 5-6
microns on a sledge microtome, deparaffinization on a
thermostat, and staining with hematoxylin and eosin.
It is the most common method of staining histological
sections. Paraffin sections are deparaffinized in
chloroform and washed in distilled water, then a
hematoxylin solution is poured onto the sections for 3
minutes. Rinse in tap water for 10 minutes and the
sections are stained with eosin from 0.2 to 3 minutes,
depending on the thickness of the sections. They are
dehydrated in alcohols of increasing concentration,
starting from 70º to 96º, clarified in carbol-xylene,
xylene, and placed in a balm. Result: cell nuclei are
stained blue-violet, the cytoplasm is pink. The method
of luminescent microscopic examination [19].
Statistical analysis. The data obtained were statistically
processed on a Pentium IV personal computer using
the Microsoft Excel program. In addition, methods of
traditional variational parametric and nonparametric
statistics were used. To establish the reliability of the
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results obtained, the coefficient t - Student test was
used. Differences were considered significant if the
frequency for the studied trait did not exceed 5% (P
<0.05). Statistical processing of digital data was carried
out using the SPSS 16.0 and Statistica 6.0 for Windows
application programs. Means and standard deviations,
medians and interquartile intervals, as well as non-
parametric methods (Mann-Whitney, Wilcoxon,
Kruskal-Wallis tests,), were determined. Analysis of the
probability of occurrence of the studied outcome in a
certain period (survival) was performed according to
the method of E. Kaplan - P. Meier. Cox stepwise
regression analysis was used to identify several risk
factors for survival. Analysis of the accuracy and
practical value of prognostic factors and the validity of
the models were measured by the method of
concordant (c-statistic) statistics (estimation of the
area under the ROC curve).
Results. The div divweight before the experiment
varied from 220 to 250 g. Group 1 - intact animals (10
rats each), served as controls for groups 3 and 4. 2nd
group
–
the creation of an experimental model of a
diabetic foot, against the background of alloxan
diabetes; To do this, 10 rats were injected
intraperitoneally with 2% alloxan in an amount of 20 mg
/ 100 g. In this experimental group, in the 2nd
experimental group, 8 rats died in the first 3 days as a
result of hyperglycemic and hypoglycemic coma, which
amounted to 80%. When examining the level of glucose
in the blood with a glucometer of the remaining rats, it
was 33.3 mmol/l and may have been higher, since the
maximum range of the glucometer is 33.3 mmol/l. The
remaining 2 rats sat in the corner, there were no
reactions to external stimuli, they were sedentary
when picked up. The animals did not touch the food.
On the next day 4, the remaining rats died.
The second series of the second group of the
experimental model of diabetes mellitus was created
based on alloxan at a dose of 15 mg per 100 g from 10
rats. In this series of experiments, in the first 3 days the
lethality was 50% (5 rats). The glucose levels of the
survivors (5 rats) ranged from 29.8 to 33.3 mmol/l.
During the next 4 days, the remaining rats died.
3rd series of the experiment of the 2nd group -
administration of alloxan intraperitoneally at a dose of
12 mg per 100 g per 100 rats. During the next 72 hours,
no lethal outcome was observed in rats, the range of
blood glucose levels in rats varied between 15.5 - 17
mmol/L. In rats on the skin of the footpad pad of the
right hind paw, a full-thickness rectangular wound
measuring 2 mm × 5 mm was created with a scalpel.
Rats were randomly divided into 2 groups, each group
of 50 rats. So it was created 3
–
a control group on 50
rats and 4 experimental groups n=50 rats. In both
groups, until the end of the experiment (17 days), no
death was recorded.
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Visual inspection. The first signs of diabetes were
manifested in the form of a sharp increase in water
consumption of 70-80 ml, polyphagia, polyuria,
hyperglycemia. With alloxan-induced diabetes mellitus
in animals during the experiment, lethargy, apathy, low
activity, tarnishing and loss of coat, weight loss,
clouding of the pupil and sclera, small-point erosion in
the tails and limbs were noted. The wool of animals
normally has a peculiar luster and is usually adjacent to
the skin. In dynamic observation in rats of the
experimental group, by the seventh day, the condition
began to improve.
In the study of indicators characterizing the state of
various organs, for example, indicators of the state of
liver cells and the degree of their damage are the
activity of AST and ALT enzymes. In our studies, the
activity of these enzymes in the blood of animals in
both groups was significantly higher than in intact
animals (ALT-34U/l±1.ASTAsT-33.4 U/l±1.1), Although, it
should be noted that already after three injections of
the drug rheomannisol, in the animals of the
experimental group, the ALT and AST enzymes
recorded
low
numbers
(52.6±1.6;
48.4±1.4,
respectively) compared with the control group (82.8±
1.4, 86.3±1.5). By the 7th day in the control group ALT-
79±0.ASTAsT-79±1.5, which is 1.8 times more than in
the experimental group - ALT-44.7±0.94 AST AST-43,
3±1.0. In our study, in animals, the degree of elevation
of the levels of enzymes alanine transferase and
aspartate transferase indicates a pronounced violation
of the cellular structure of the liver. Recorded
activation of transaminases may indicate a violation of
the integrity of hepatocyte membranes, leading to an
increase in their permeability, and subsequently to the
death of liver cells. A decrease in the activities of both
enzymes (ALT, AST) followed the injections of
rheomannisol in the experimental gr, out and on the
10th and 14th days, the numbers (ALT-37.5±0.62, AST-
37.1±0.69;
ALT-35.3±
0.54,
AST-34.9
±
1.04,
respectively) indicate the normalization of the
functional capacity of the liver, while in the control
group, the activity of ALT and AST enzymes even on
days 10, 14 (ALT-75.5 ± 1.1, AST-74.4±1.6; ALT-57.2±1.2,
AST-53.4±1.3, respectively) 2 times higher than in the
experimental one, and remain at a high level until the
end of the experiment (Table 1 ).
Table 1. Biochemical parameters of animal blood in an experimental model of diabetic foot.
Indexes
Glucose,
mmol/l
ALT, U/l
AST, U/l
Urea,
mmol/l
Creatinine
, mkmol/l
Total
protein, g/l
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Group of
animals
1 day
Intact
5,8+0,19
34,0+1,0
33,4+1,1
5,1+0,20
61,5+2,0
74,1+1,2
Control
16,6±0,29
**
*
75,1±1,8
***
72,7±1,3
**
*
13,8±0,27
***
142,6±2,4
***
58,4±1,0
***
Main
15,2±0,43
**
*^
70,4±1,0
***
^
66,7±1,1
**
*^^
13,5±0,27
***
141,0±3,3
***
58,8±0,63
**
*
3 days
Control
15,4±0,28
**
*
82,8±1,4
***
86,3±1,5
**
*
15,0±0,40
***
145,7±1,8
***
55,5±0,73
**
*
Main
12,0±0,31
**
*^^^
52,6±1,6
***
^^^
48,4±1,4
**
*^^^
9,8±0,29
**
*^^^
97,6±2,1
**
*^^^
60,1±0,86
**
*^^^
7 days
Control
14,1±0,20
**
*
79,0±0,93
**
*
79,0±1,5
**
*
12,8±0,20
***
127,6±1,8
***
59,4±0,51
**
*
Main
9,0±0,37
***
^^^
44,7±0,94
**
*^^^
43,3±1,0
**
*^^^
7,2±0,30
**
*^^^
78,2±2,6
**
*^^^
66,0±1,4
***
^^^
10 days
Control
13,8±0,16
**
*
75,5±1,1
***
74,4±1,6
**
*
12,2±0,24
***
113,2±2,4
***
63,3±0,71
**
*
Main
7,3±0,21
***
^^^
37,5±0,62
*^
^^
37,1±0,69
*^^^
5,8±0,19
*^
^^
68,7±1,2
*^
^^
73,5±0,80
^^
^
14 days
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Note: *- significantly compared with the intact group (*-P<0,05; **-P<0,01; ***-P<0,001)
^ - significantly compared with the control group (^-P<0,05; ^^-P<0,01; ^^^-P<0,001)
One of the laboratory signs of the development of
renal dysfunction indicates the content of urea and
creatinine in the blood plasma, in the first days of the
experiments, in rats of the experimental and control
groups were almost 2.5 times (without significant
differences between these groups) higher than in the
intact group (tables No. 1). After 3-fold intraperitoneal
administration of the drug reomannisol, on the 3rd day,
the experimental group showed a noticeable decrease
in the values of urea (9.81±0.29) and creatinine
(97.6±2.1) by 1.5 times relative to the values control
group (urea-15.0±0.40; creatinine-145.7±1.8). On the
7th day in the groups of rats treated with reomannisol,
the levels of urea and serum creatinine (7.2±0.30 and
78.2±2.6, respectively) were lower compared to
control animals (12.8±0. 20 and 127.6±1.8, respectively)
by almost 1.7 times. On days 10, 14, urea values and
creatinine clearance (urin-5.8±0.19; creat-68.7±1.2;
urine-5.2±0.22; creat-63.8±1.3 respectively) in the
experimental group were close to those of the intact
group of rats (urea-5.1±0.20; creatinine-61.5±2.0).
However, in the control group, it was accompanied by
a higher value of urea and creatinine clearance, and on
the 14th day, they were urea-9.7±0.30 and creatinine-
96.7±1.6 - an average of 1.7 times higher than the values
of the experimental group (Table 1).
Evaluated at the end of the study on the background
of therapy with the studied preparations of
reomannisol, based on the results obtained, we can say
about the positive effect of the drug on renal activity,
as well as on protein metabolism.
Table 2. The product of POL is malonic dialdehyde (MDA).
Control
12,9±0,19
**
*
57,2±1,2
***
53,4±1,3
**
*
9,7±0,30
**
*
96,7±1,6
**
*
68,3±0,57
**
*
Main
6,5±0,13
*^^^
35,3±0,54
^^
^
34,9±1,04
^^^
5,2±0,22
^^
^
63,8±1,3
^^
^
75,8±0,63
^^
^
Days
Control group,
mkmol/l.
Main group, mkmol/l.
Intact group,
mkmol/l.
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03
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P
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:
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SJIF
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FACTOR
(2021:
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)
(2022:
5.
893
)
(2023:
6.
184
)
OCLC
–
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Note: *- significantly compared with the intact group (*-P<0,05; **-P<0,01; ***-P<0,001)
^ - significantly compared with the control group (^-P<0,05; ^^-P<0,01; ^^^-P<0,001)
Under the conditions of the model we have chosen,
the state of the LPO-MDA system was also studied
since this system is a key link in the pathogenesis of
diabetes mellitus. On the 1st day of the experiment, the
content of malondialdehyde was significantly higher in
both groups compared to intact rats (0.87 ± 0.02),
which indicates the formation of a large amount of lipid
peroxidation products, indicating the processes of
destruction of cell membranes (Table 2). The effect of
daily administration of reomannisol at a dose of 1
ml/100 g (experimental group) on the intensity of lipid
peroxidation on the 7th day was expressed by a
noticeable decrease in the content of MDA (1.02 ± 0.01)
by 1.2 times relative to the control group (1.27 ±0.01).
At the end of the experiment (day 14) in the group
receiving traditional treatment, the animals retained a
high level of MDA-1.17 ± 0.01, indicating a high content
of free radicals in the animal div. While in the
experimental group there is a stable decline in the level
of MDA and on the 10th, 14th day fixes a normal level
of MDA (respectively 0.93±0.01; 0.90±0.02). This result
indicates the antioxidant, detoxifying effect of the
drug reomannisol, which is characteristic of it.
MWM isolated from blood plasma and erythrocytes in
rats modeled with diabetes mellitus by alloxan can
activate LPO processes in the membranes of animal
erythrocytes. The state of endointoxication is
characterized, as a rule, by the activation of lipid
peroxidation, and they also act as a factor in the
aggravation of EI processes [7, 8].
Thus, judging from Table 3, high content of MWM
products, which cause the development of
endotoxemia, was found in the blood. It was revealed
that at the beginning of the experiment, the content of
MWM in blood plasma and erythrocytes in animals of
both groups was approximately 1.7-2 times higher than
in the intact group (see Table 3). It can also be said,
1
1,39±0,02
***
1,35±0,02
***
0,87±0,02
3
1,43±0,02
***
1,09±0,01
***^^^
-
7
1,27±0,01
***
1,02±0,01
***^^^
-
10
1,22±0,01
***
0,93±0,01
*^^^
-
14
1,17±0,01
***
0,90±0,02
^^^
-
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P
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:
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SJIF
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(2022:
5.
893
)
(2023:
6.
184
)
OCLC
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reliably given by this table, that the numbers of the
toxemia index in plasma and erythrocytes are higher
than those in the intact group. The peptide component
of MWM is represented by the content of
oligopeptides in plasma and erythrocytes in both
groups, which also significantly exceeded by 1.6
–
2.4
times the value in the group of relatively intact animals.
This may indicate the activation of pathological
proteolysis processes. After the use of reomannisol,
the experimental group showed a tendency to reduce
all indicators of endogenous intoxication. By the 7th
day, the indices of MWM, OP of plasma (pl.) and
erythrocytes (eryt.) in the control group were on
average 1.2 times higher than those of the
experimental group. At 10, 14 days in the experimental
- fix the values of indicators corresponding to the intact
group and the normalization of the pathological
process in the div. Animals that received only
traditional treatment, EI indicators remain elevated on
average 1.2 times than in the experimental group, and
the state of intoxication persists until the end of the
experiment.
Table 3. Dynamics of change in indicators of endogenous intoxication.
Serum
Erythrocytes
Medium
weight
molecule
s
(MWM)
of
plasma,
Conv.
unit
Oligopeptid
es (OP) of
plasma, g/l
Toxemic
index (TI)
of plasma,
conv. unit
Intoxication
index (II)
conv. unit
Medium
weight
molecules
(MWM)
of eryt.,
conv. unit
Oligopeptid
es (OP) of
eryt., g/l
Toxemic
index (TI)
of eryt,
conv. unit
SCE, %
Intact
group
3,6±0,24
0,45±0,04
1,81±0,20
3,57±0,36
3,5±0,21
0,68±0,04
2,28±0,40
7,8±0,43
Contr
ol
group
Day 1
6,1±0,22
*
**
0,78±0,06
***
4,41±0,55
*
**
12,04±0,62
*
**
7,3±0,25
**
*
1,16±0,07
***
7,79±0,62
**
*
12,8±0,67
**
*
Main
group
Day 1
6,1±0,17
*
**
0,77±0,04
***
4,20±0,21
*
**
11,54±0,67
*
**
7,0±0,16
**
*
1,12±0,07
***
7,44±0,36
**
*
12,7±0,47
**
*
Contr
ol
group
Day 3
5,6±0,16
*
**
0,70±0,05
***
3,73±0,45
*
*
10,64±0,46
*
**
6,4±0,19
**
*
1,02±0,06
***
7,21±0,22
**
*
11,7±0,35
**
*
Main
group
5,3±0,09
*
**
0,69±0,05
**
3,36±0,28
*
**
8,71±0,99
**
*
5,9±0,08
**
*^
0,96±0,06
***
5,54±0,65
**
*^
10,4±0,44
**
*^
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03
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)
(2022:
5.
893
)
(2023:
6.
184
)
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Day 4
Contr
ol
group
Day 7
5,3±0,11
*
**
0,67±0,05
**
3,09±0,22
*
**
8,51±0,35
**
*
5,6±0,11
**
*
0,92±0,05
**
5,79±0,32
**
*
9,6±0,31
**
Main
group
Day 7
4,0±0,11
^
^^
0,58±0,02
*
2,15±0,26
^
5,61±0,62
*^
^^
4,1±0,11
*^
^^
0,78±0,04
^
3,46±0,36
*^
^^
8,3±0,17
^^
Contr
ol
group
Day 10
4,9±0,10
*
**
0,56±0,03
*
2,83±0,23
*
*
6,84±0,31
**
*
5,2±0,11
**
*
0,85±0,05
*
4,64±0,23
**
*
9,3±0,21
**
Main
group
Day 10
3,7±0,14
^
^^
0,48±0,05
1,86±0,22
^
^
3,65±0,24
^^
^
3,7±0,12
^^
^
0,72±0,05
^
2,43±0,17
^^
^
8,0±0,23
^^^
Contr
ol
group
Day 14
4,2±0,11
*
0,52±0,03
2,39±0,15
*
5,56±0,24
**
*
4,2±0,10
**
0,77±0,04
3,30±0,16
*
8,7±0,17
*
Main
group
Day 14
3,5±0,18
^
^
0,45±0,04
1,80±0,23
^
3,55±0,37
^^
^
3,2±0,17
^^
^
0,68±0,02
2,30±0,22
^^
7,8±0,43
^
Note: *- significantly compared with the intact group (*-P<0,05; **-P<0,01; ***-P<0,001)
^ - significantly compared with the control group (^-P<0,05; ^^-P<0,01; ^^^-P<0,001).
The study of the sorption capacity of erythrocyte
membranes was carried out on erythrocytes from 10
practically healthy rats. The mean SCE in this group was
7.8% ± 0.43. After the administration of alloxan to the
div of rats, in both groups on the first days, a regular
increase in SCE was observed on average by 1.6 times,
intoxication index was 3.3 times that in the intact atop.
The redistribution of the toxic load between plasma
and blood erythrocytes is a necessary part of the
div's natural detoxification [2, 10]. Endotoxins bind
to the transmembrane protein of erythrocytes -
glycophorin, and in this form are transported to the
detoxification organs.
As a result, the use of reomannisol intraperitoneally in
rats of the experimental group improved the condition
of the animals, reduced the EI of the div. By 10, 14
days in the control group Intoxication index (II)
6.84±0.31; 5.56±0.24 and SCE 9.3±0.21; 8.7 ± 0.17,
respectively, were, on average, 1.7 (II) and 1.1 (SCE)
higher than the values of the experimental group - II
3.65 ± 0.24; 3.55±0.37 and SCE 8.0±0.23; 7.8±0.43 (see
table No. 3). This is due to the fact because the qualities
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(2023:
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of an antioxidant that improves blood rheology, a
detoxifying effect (enterosorbent), and a diuretic,
which have the effect of "biochemical sanitation" and
restores the physiological functions of cells for the
biotransport of endotoxins.
Wound healing is a big problem for diabetic patients.
This problem is observed both on a cellular and
humoral basis.
When examining the wound, the following parameters
of the course of the wound process were taken into
account: the presence and nature of the inflammatory
reaction, the presence and nature of the scab, the
strength of its adherence to the underlying tissues, the
severity of perifocal inflammation, skin hyperemia and
tissue infiltration in the wound area, the condition of
the edges and bottom of the wound, the timing of
wound cleansing from necrotic tissues and the
appearance of granulations, the nature of granulation
tissue, the timing of the onset of epithelization of
wounds. At 24 hours post-injury in both experimental
groups, the size of the wound increased in both groups
as the edges of the wounds were stretched further
apart due to edema, the edema spread to the entire
foot (Figure 1). Also, in both groups on the 2nd day
after the formation of a model of a rectangular skin
wound, it is observed that the surface of the wound
defect was covered with a thin scab formed by wound
discharge. When taking the animal in hand, the crust
was easily damaged, a transparent exudate leaked out.
Pronounced signs of inflammation are noted: the
edges of the wound are edematous, hyperemic with
areas of necrosis, the bottom of the wound is covered
with areas of fibrin.
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)
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Figure 1. Images of foot wounds on days 1, 3 after injury and comparison of the size (area) of wounds between
control and experimental groups.
When analyzing the results of planimetric studies of
the speed epithelialization of wound defects, on the
3rd day of the experiment, there were no particular
differences in the groups. In both groups, on the 3rd
day, wound defects in animals were covered with a
dense dark-colored scab, inflammation persisted.
When viewed perifocally from the wound, bulging of
the skin was determined in both groups. But it should
be noted that during the revision of the wound in the
control group, the scab was easily removed from the
wound relative to the experimental group, under the
scab - the tissue was dull in places, there was a layer of
fibrin, there were areas of necrosis. Also, it should be
noted that the experimental group showed a decrease
in edema and hyperemia of the edges and walls of
wounds - it is on the decline, the beginning of the
formation of angiogenesis and elements of granulation
from the bottom of the wound can be traced,
compared with the control group.
Table 4. Comparative results of wound healing in animals with an experimental model of diabetic foot.
Control group
Main group
No
Wound size,
mm
Wound
area
mm
2
Popov
value
%
Wound size, mm
Wound
area mm
2
Popov
value %
1
2,0±0,
03
5,0±0,
02
10,1±0,
16
-
2,0±0,0
3
5,0±0,0
2
10,1±0,1
6
-
3
1,9±0,
02
4,7±0,
02
8,6±0,0
8
5,0±0,
27
1,7±0,0
2
***
4,5±0,0
2
***
7,4±0,05
*
**
8,9±0,46
**
*
7
1,7±0,
02
4±0,02 6,5±0,0
7
6,1±0,
30
1,5±0,0
2
***
3,0±0,0
2
***
4,3±0,05
*
**
10,3±0,18
*
**
10
1,6±0,
02
3,2±0,
02
4,9±0,0
5
8,4±0,
21
-
-
-
-
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Note: *- significantly compared with the control group (*-P<0,05; **-P<0,01; ***-P<0,001)
In the experimental group, the scab was difficult to
detach, tissues in places with a slight overlay of fibrin.
Swelling in the area of the foot wound continued in the
rats of the control group on the 7-8th day, but in the
rats of the experimental group, it decreased already on
the 5th day after the injury. From table 4 it follows that
on the 7th day after the injury in rats from the
experimental group when using the drug, there was a
significant decrease in the area of the wounds (4.3 ±
0.05 mm2) 2 times than its original wound, and 1.5
times than in rats of the control group (6.5±0.07 mm2),
due to wound contraction and marginal epithelization
(Figure 6). The crust from the wound was removed
with great difficulty, under it there was a brightly
granulating wound defect with pronounced signs of
marginal epithelization, far ahead of the control group.
Also, in the rats of the experimental group, almost
complete closure of the wound defect is observed, it is
noted that the wound is bleeding well, this indicates an
improvement in blood circulation in the wound, which
exceeds this indicator over the control group. When
examining the histological section of the wound under
a microscope, there is a limitation and rejection of the
destructive-necrotic tissue on the surface of the
wound (Figure 3). At the same time, in the
circumference of the wound, the tissue of the
epidermis is compacted and the focus of destruction of
the dermis is delimited from the underlying healthy
elements of the tissue of the dermis. As part of the
destructive tissue, the development of the process of
disintegration and disorganization of both cellular and
fibrous structures is determined. In the underlying
connective tissue of the dermis, a neoplasm of hair
follicles, compaction of fibrous structures and an
increase in the proliferative activity of histiocytic cells
are determined.
Figure 2. Control group, Day 7. Diabetic wound. Preservation of necrotic mass and inflammatory infiltrate in the
bottom of the diabetic foot. Staining: hematoxylin-eosin. Magnification: 10x40.
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(2023:
6.
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)
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Figure 3. Main group, Day 7. Rejection of necrotic tissue on the surface of a diabetic wound. Staining: hematoxylin-
eosin. Magnification: 10x40.
Figure 4. Control group, Day 10. Diabetic wound. Formation of a dense inflammatory infiltrates around the wound
of a diabetic foot. Staining: hematoxylin-eosin. Magnification: 10x40.
Figure 5. Main group, day 10. Compaction of the surface layers of the epidermis, fibrosis of the connective tissue of
the dermis. Staining: hematoxylin-eosin. Magnification: 10x40.
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On the 7th day after treatment with the traditional
method of an experimental model of a diabetic foot in
the control group, at the bottom and circumference of
the diabetic wound, necrobiotic tissue and acute
inflammatory infiltrate are preserved in the form of a
structureless tissue mass, in the circumference of
which it is infiltrated with leukocyte cells, and a picture
of the formation of poorly differentiated (granulation)
is also found. tissue, the process of vasculogenesis is
very weak (Figure 2). As part of the structureless mass,
there are foci of edema and tissue vacuolization, as
well as hematoxylin conglomerates and calcification.
Thus,
the
development
of
microangiopathy
phenomena took place, which makes it possible to
consider diabetic microangiopathy as one of the
morphological and functional manifestations of
diabetes mellitus.
Figure 6. Images of foot wounds on days 7, 10, 14 after injury and comparison of the size (area) of wounds between
control and experimental groups.
By the 10th day in the experimental group, who
received traditional treatment and Reomanisol, an
independent almost complete closure of the wound
defect and hair growth around the wound were noted
(Figure 6). There is a rejection of the necrotic part of
the epidermal tissue, dedifferentiation of the
remaining part of the stratified epithelium in the form
of compaction of the surface layers, vacuolization, and
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an increase in the proliferative activity of the cells of
the basal layers (Figure 5). The connective tissue of the
dermis is compacted, without signs of an acute
inflammatory process, the fibrous structures are
transformed into dense, homogeneous, fibrous
masses due to disorganization and fusion with each
other. In them, cellular structures are localized along
the periphery and around the vessels, and they are in a
proliferative active state. On the 10th day after the
treatment of diabetic foot with reomannisol,
regeneration
of
the
integumentary
stratified
epithelium is noted in the form of sliding of epithelial
cells onto the surface of the wound. At the same time,
the epidermis is represented in the regeneration zone
by several layers of active and hyperchromic
epitheliocytes. Under the epidermis, the formation of
a basement membrane from loose fibrous structures is
determined. In the tissue of the dermis, the presence
of foci of reparative regeneration is determined in the
form of excessive formation of fibrous, cellular
structures that differ from the surrounding tissue by
the presence of many vessels and proliferatively active
histiocytic cells. Both in the epidermis and the dermis,
there are no signs of an acute inflammatory process.
In the control group, on the 10th day, a wound defect
of about 4.9 ± 0.05 mm2 remains (Figure 6). At the
bottom and in the circumference of the wound, the
formation of inflammatory granulation tissue with foci
of necrosis and hemorrhage is noted. The
inflammatory infiltrate is represented by proliferatively
active lymphoid and histiocytic cells (Figure 4),
randomly arranged fibrous structures consisting of
argyrophilic and collagen fibers. In the center of the
inflammatory infiltrate, a defect surrounded by
fibrinoid necrosis and a homogeneous fibrous mass is
determined. In the circumference of the inflammatory
infiltrate, the connective tissue is subjected to edema,
loosening with the breakdown of fibrous structures,
and cell necrobiosis. The wound healed on the 14th day
of the experiment (Figure 6). Thus, hyperglycemia
causes microvascular complications due to impaired
angiogenesis, which leads to a prolongation of the
inflammatory effect of the wound and the period of
wound healing.
The use of standard wound treatments (iodine and
levomekol) and the drug reomanisol, indicators of
planimetric control ovethroughoute the wound
process in animals of this group (experimental) are at
a consistently high level.
CONCLUSIONS
1. The best option for creating an experimental model
of a diabetic foot is the introduction of alloxan
intraperitoneally in a single dose of 12 mg per 100 g, in
which moderate diabetes develops.
2. After using the drug reomannisol intraperitoneally at
a dose of 1 ml / 100 g 1 time per day for 5 days, there
was a sharp decline in EI numbers. On the 10th day, the
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5.
694
)
(2022:
5.
893
)
(2023:
6.
184
)
OCLC
–
1121105677
Publisher:
Oscar Publishing Services
Servi
EI values in the experimental group returned to
normal, similar to those in the intact group. The drug
reomannisol performs "biochemical rehabilitation",
due to its inherent qualities: antioxidant, improves
blood rheology, detoxification, and diuretic. In rats of
the control group, the EI numbers remain at high levels
until the end of the experiment.
3. The results of biochemical studies demonstrate
positive dynamics in experimental animals with a
diabetic foot model when using the drug reomannisol.
This was manifested by the fact that by the 10th day
there was a decrease and normalization of the level of
glucose in the peripheral blood, indicators of renal
clearance (urea, creatinine), liver (ALT, AST, albumins).
4. An open, full-thickness wound of the foot, in rats
with DM, had low blood circulation, prolonged
inflammation, and was characterized by a violation of
the inflammatory and proliferative phases of the
healing
process,
which
is
associated
with
hyperglycemia. Thus, this model of the open foot in
rats provides a good approach for studying the process
of wound healing in DM, and this model can be
regarded as creating an analog of the human diabetic
foot syndrome in an experimental model of alloxan-
induced diabetes mellitus.
5. The rate of healing of wound defects in rats with
diabetic foot syndrome in the control group falls on the
14th day, since the terms of resorption and rejection of
necrotic tissues in the wound are lengthened, damage
to
the
vessels
of
the
microvasculature
(microangiopathy), edema is observed for a long time.
The wounding process against the background of DM
is characterized by the late formation of angiogenesis,
slowing down and impaired maturation of granulation
tissue, marginal epithelialization. In the experimental
group, in rats, along with the local traditional method
of wound treatment, the drug reomannisol was used
intraperitoneally, as a result, wound healing was
recorded on the 10th day from the moment the wound
was applied to the foot of the rats. The use of local
treatment and reomannisol can enhance angiogenesis
in the early stages of the experiment and restore
disturbed microcirculation (neoplasms of blood
vessels), increase macrophage response, fibroblast
proliferation,
maturation
and
remodeling
of
granulation tissue and its epithelization, reduce the
inflammatory reaction, which leads to more effective
and early healing wound area.
6. Comprehensive treatment (application of a local
traditional method of treatment on the wound and the
drug reomannisol) in an experimental model of the
diabetic foot have positive effects on reparative
processes and wound healing, due to the formation
and enhancement of angiogenesis, as well as on the
functional parameters of vital organs by reducing
intoxication organism.
Volume 03 Issue 11-2023
85
International Journal of Medical Sciences And Clinical Research
(ISSN
–
2771-2265)
VOLUME
03
ISSUE
11
P
AGES
:
65-88
SJIF
I
MPACT
FACTOR
(2021:
5.
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)
(2022:
5.
893
)
(2023:
6.
184
)
OCLC
–
1121105677
Publisher:
Oscar Publishing Services
Servi
Ethical approval. Operations and all manipulations with
animals were carried out using general anesthesia, in
compliance with the principles of humanity outlined in
the
directives
of
the
European
Community
(86/609/EEC) and the Declaration of Helsinki, by the
"Rules for working with experimental animals". The
ethical approval for the study was granted by Tashkent
Medical Academy and the Committee of Ethical
Approval for Researches under the Ministry of Health
of the Republic of Uzbekistan.
Conflict of interest. The authors declare that they have
no competing interests.
Funding.
No funding sources to declare.
REFERENCES
1.
. Эрназаров, Х. И., & Эргашев, У. Ю. (2022).
ВЛИЯНИЕ ПРЕПАРАТА «РЕОМАННИСОЛ» НА
ЗАЖИВЛЕНИЕ
РАН
ПРИ
ЭКСПЕРИМЕНТАЛЬНОЙ
МОДЕЛИ
ДИАБЕТИЧЕСКОЙ СТОПЫ. Печатается по
решению
редакционно
-
издательского
совета ФГБОУ ВО КГМУ Минздрава России,
52.
2.
. Эрназаров, Х. И., & Эргашев, У. Ю. (2022).
ЛИКВИДАЦИЯ
ЭНДОГЕННОЙ
ИНТОКСИКАЦИИ
С
ПОМОЩЬЮ
ОТЕЧЕСТВЕННОГО
ПРЕПАРАТА
«РЕОМАННИСОЛ»
ПРИ
ЭКСПЕРИМЕНТАЛЬНОЙ
МОДЕЛИ
ДИАБЕТИЧЕСКОЙ СТОПЫ. Печатается по
решению
редакционно
-
издательского
совета ФГБОУ ВО КГМУ Минздрава России,
55.
3.
.
Эрназаров,
Х.
И.
(2022).
ЭКСПЕРИМЕНТАЛЬНО
-
МОРФОЛОГИЧЕСКОЕ
ОБОСНОВАНИЕ
ИСПОЛЬЗОВАНИЯ
РЕОМАННИСОЛА
В
ЛЕЧЕНИИ
ЭКСПЕРИМЕНТАЛЬНОЙ
МОДЕЛИ
ДИАБЕТИЧЕСКОЙ СТОПЫ.
4.
. Эрназаров, Х. И., Турсуметов, А. А., &
Садыков, Р. А. (2018). Оценка эффективности
биопокрытий
в
лечении
ожогов
в
эксперименте. In Роль больниц скорой
помощи
и
научно
исследовательских
институтов в снижении предотвратимой
смертности среди населении (pp. 111
-112).
5.
. Аталиев, А., Муродов, А., Шатемиров, В.,
Холов, X., Эрназаров, X., & Маликов, Н. &
Атабаев, K.(2017). Улучшение результатов
комплексного лечения гангрены фурнье с
применением
со
2
лазера
и
фотодинамической
терапии.
Журнал
проблемы биологии и медицины,(1 (93)), 30
-
32.
6.
. Тешаев, O., Холов, X., Бобошарипов, Ф.,
Амонуллаева, З., Эрназаров, X., & Баратов, Н.
(2017). Современные аспекты диагностики и
патогенеза острых панкреатитов. Журнал
Volume 03 Issue 11-2023
86
International Journal of Medical Sciences And Clinical Research
(ISSN
–
2771-2265)
VOLUME
03
ISSUE
11
P
AGES
:
65-88
SJIF
I
MPACT
FACTOR
(2021:
5.
694
)
(2022:
5.
893
)
(2023:
6.
184
)
OCLC
–
1121105677
Publisher:
Oscar Publishing Services
Servi
проблемы биологии и медицины, (1 (93)),
202-206.
7.
. Зохиров, А. Р., & Эрназаров, Х. И. (2022,
June).
Патоморфологическая
картина
жизненноважных
органов
при
экспериментальной модели диабетической
стопы. In International scientific forum
-2022
(pp. p146-153).
8.
. Эрназаров, Х., Зохиров, А., Эргашев, У. Ю., &
Исраилов,
Р.
(2022).
ПАТОМОРФОЛОГИЧЕСКАЯ
КАРТИНА
ЖИЗНЕННО
ВАЖНЫХ
ОРГАНОВ
ПРИ
ЭКСПЕРИМЕНТАЛЬНОЙ
МОДЕЛИ
ДИАБЕТИЧЕСКОЙ СТОПЫ.
9.
. Зохиров, А. Р., Эрназаров, Х. И., & Эргашев,
У.
Ю.
(2022,
January).
ПАТОМОРФОЛОГИЧЕСКИЕ ОСОБЕННОСТИ
ЗАЖИВЛЕНИЯ
РАН
ПРИ
ЭКСПЕРИМЕНТАЛЬНОЙ
МОДЕЛИ
ДИАБЕТИЧЕСКОЙ СТОПЫ. 64
-
ОЙ НАУЧНО
-
ПРАКТИЧЕСКОЙ
КОНФЕРЕНЦИИ
ОБУЧАЮЩИХСЯ «НАУКА И ЗДОРОВЬЕ»
ПОСВЯЩЕННАЯ ДНЮ НАУКИ РЕСПУБЛИКИ
КАЗАХСТАН
С
МЕЖДУНАРОДНЫМ
УЧАСТИЕМ.
10.
. Zohirov, A. R., Ergashev, U. Y., & Ernazarov, H.
I. (2022, June). Qandli diabetda oyoqning
yiringlinekrotik
shikastlanishlarining
patomorfologik jihatlarini kompleks davolashni
o'rganish. In International scientific forum-2022
(pp. p132-136).
11.
. Эрназаров, Х. И., Эргашев, У. Ю., Зо
ҳ
иров
,
А
.
Р
., &
Каримов, Х. Я. (2022). ЭФФЕКТИВНОСТЬ
ИСПОЛЬЗОВАНИЕ
ПРЕПАРАТА
РЕОМАННИСОЛ
В
ЛЕЧЕНИИ
ЭКСПЕРИМЕНТАЛЬНОЙ
МОДЕЛИ
ДИАБЕТИЧЕСКОЙ СТОПЫ.
12.
. Ergashev, U. Y., Mustafakulov, G. I., Muminov,
A. T., Minavarkhujaev, R. R., Yakubov, D. R.,
Ernazarov Kh, I., & Zohirov, A. R. (2021). The
role of minimally invasive technologies in the
treatment of liver cavities. Frontiers in
Bioscience-Landmark, 8, 82-89.
13.
. Ergashev, U. Y., Mustafakulov, G. I., Mominov,
A. T., Yakubov, D. R., Zohirov, A. R., &
Ernazarov,
X.
I.
(2022).
Effective
of
Simultaneous Surgeries in Chronic Immune
Thrombocytopenia.
14.
. Ergashev, U. Y., Zokhirov, A. R., & Ernazarov,
K.
I.
(2022).
THE
STUDY
OF
PATHOMORPHOLOGICAL
DIAGNOSIS
OF
VITAL ORGANS AFTER MODERN TREATMENT
OF DIABETIC FOOT SYNDROME.
15.
. Ergashev, U. Y. (2022). Ernazarov Kh. I.,
Zohirov AR, Alzabni ID 2022. Complex
Treatment of Experimental Model of Diabetic
Foot Syndrome. American Journal of Medicine
and Medical Sciences, 12(5), 471-480.
Volume 03 Issue 11-2023
87
International Journal of Medical Sciences And Clinical Research
(ISSN
–
2771-2265)
VOLUME
03
ISSUE
11
P
AGES
:
65-88
SJIF
I
MPACT
FACTOR
(2021:
5.
694
)
(2022:
5.
893
)
(2023:
6.
184
)
OCLC
–
1121105677
Publisher:
Oscar Publishing Services
Servi
16.
. Ergashev, U. Y., Zokhirov, A. R., & Ernazarov,
K. I. (2022). THE STUDY OF DIAGNOSTICS AND
PREVENTION
OF
PATHOPHYSIOLOGICAL
PARAMETERS AFTER MODERN TREATMENT
OF PURULENT-NECROTIC PROCESSES IN
DIABETIC.
17.
. Yusufjanovich, E. U., Rafiqovich, Z. A., &
Irsalievich, E. K. (2023). Assessment of the
Process of Epithelialization After Complex
Treatment of Diabetic Foot Syndrome. Texas
Journal of Medical Science, 16, 19-23.
18.
. Хайитов, И. Б., Эрназаров, Х. И., Маликов, Н.
М., & Зохиров, А. Р. (2023). ЭХИНОКОКК И
ЕГО ЗНАЧЕНИЕ В ХИРУРГИИ.
19.
. Эргашев, Улугбек Юсуфжонович, Санжар
Мавлянов, and Хожимурод Эрназаров.
"ПУТИ
УЛУЧШЕНИЯ
ОКАЗАНИЯ
АМБУЛАТОРНОЙ
ХИРУРГИЧЕСКОЙ
ПОМОЩИ
В
ПЕРВИЧНОМ
ЗВЕНЕ
ЗДРАВООХРАНЕНИЯ." (2022).
20.
. Эрназаров, Х. И., & Эргашев, У. Ю. (2022).
УСТРАНЕНИЕ
ЭНДОГЕННОЙ
ИНТОКСИКАЦИИ
С
ПОМОЩЬЮ
ОТЕЧЕСТВЕННОГО
ПРЕПАРАТА
РЕОМАННИСОЛ
ПРИ
ЭКСПЕРИМЕНТАЛЬНОЙ
МОДЕЛИ
ДИАБЕТИЧЕСКОЙ СТОПЫ. In Приоритетные
направления развития спорта, туризма,
образования и науки (pp. 866
-869).
21.
. Эргашев, Улугбек Юсуфжонович, et al.
"Влияние основных характеристик образа
жизни на формирование неблагоприятных
показателей
здоровья
амбулаторных
пациентов хирургического профиля." (2022).
22.
.Махмудова, Н. Р. (2016). Прагматическая и
когнитивная интерпретация градации в
английском
и
узбекском
языках.
In
Актуальные проблемы филологии (pp. 107
-
109).
23.
. Ярашев, Т. Я., Кутлымурадов, А. Д., &
Эрназаров,
Х.
И.
(2019).
ТАКТИКА
ХИРУРГИЧЕСКОГО
ЛЕЧЕНИЯ
ПРИ
НЕВПРАВИМОЙ ПУПОЧНОЙ ГРЫЖЕ. Новый
день в медицине, (4), 380
-383.
24.
. Аталиев, А., Муродов, А., Шатемиров, В.,
Холов, X., Эрназаров, X., Маликов, Н., ... &
Атабаев, K. (2017). Улучшение результатов
комплексного лечения гангрены фурнье с
применением
со
2
лазера
и
фотодинамической
терапии.
Журнал
проблемы биологии и медицины, (1 (93)), 30
-
32.
25.
. Зохиров, А. Р., & Набиева, А. Ш. (2023).
ИЗУЧЕНИЕ
ПАТОМОРФОЛОГИЧЕСКИХ
ОСОБЕННОСТЕЙ СОВРЕМЕННОГО ЛЕЧЕНИЯ
ГНОЙНО
-
НЕКРОТИЧЕСКИХ ПРОЦЕССОВ ПРИ
САХАРНОМ ДИАБЕТЕ. Interpr
etation and
researches, 1(2), 25-36.
Volume 03 Issue 11-2023
88
International Journal of Medical Sciences And Clinical Research
(ISSN
–
2771-2265)
VOLUME
03
ISSUE
11
P
AGES
:
65-88
SJIF
I
MPACT
FACTOR
(2021:
5.
694
)
(2022:
5.
893
)
(2023:
6.
184
)
OCLC
–
1121105677
Publisher:
Oscar Publishing Services
Servi
26.
. Зохиров, А. Р. (2023). ОБОСНОВАНИЕ
ПРОЦЕССОВ
ЭПИТЕЛИЗАЦИИ
И
РЕГЕНЕРАЦИИ
ПРИ
ГНОЙНО
-
НЕКРОТИЧЕСКИХ
ПРОЦЕССАХ
НИЖНИХ
КОНЕЧНОСТЕЙ ПРИ САХАРНОМ ДИАБЕТЕ.
Conferencea, 174-180.
27.
. Rafiqovich, Z. A. (2023). OBSERVATION OF
BIOCHEMICAL RESULTS IN Ravshanovna, M. N.
(2022).
LINGUCULTUROLOGICAL
AND
COGNITIVE TRANSLATION PROBLEMS OF
ABDULLA QADIRIY'S" BYGONE DAYS". Berlin
Studies Transnational Journal of Science and
Humanities,
2(1.6
Philological
sciences).EXPERIMENTAL DIABETIC
FOOT
SYNDROME. Conferencea, 181-188.
28.
. Rafiqovich, Z. A. (2023). MONITORING OF THE
REGENERATION PROCESS IN PURULENT-
NECROTIC PROCESSES OF THE LOWER
EXTREMITIES. Conferencea, 189-194.
29.
. Rafiqovich, Z. A. (2023). STUDY OF THE
EFFECT OF LIPID PEROXIDASE ANALYSIS ON
THE BODY IN DIABETIC FOOT SYNDROME.
Conferencea, 76-82.
30.
. Rafiqovich, Z. A. (2023). CONTROL OF
INDICATORS OF ENDOTOXICOSIS IN DIABETIC
FOOT SYNDROME. Conferencea, 83-90.
31.
Ergashev,
U.
Y.,
Zohirov,
A.
R.,
Minavarkhojayev, R. R., & Mominov, A. T.
(2023).
IMPROVING
METHODS
FOR
DIAGNOSING
AND
MONITORING
ENDOTOXICOSIS IN EXPERIMENTAL DIAETIC
FOOT SYNDROME. World Bulletin of Public
Health, 19, 84-95.
