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Abstract

Objective The aim of the study was to estimate the impact of whole body cryotherapy (WBC) on oxidative stress when performed in a closed cryochamber on patients with ankylosing spondylitis (AS). Material and methods The effect of ten WBC procedures lasting 3 minutes a day with a subsequent 60-minute session kinesiotherapy on oxidative stress in male AS patients (WBC group n = 16) was investigated. To assess the disease activity, the Bath Ankylosing Spondylitis Diseases Activity Index (BASDAI) and Bath Ankylosing Spondylitis Functional Index (BASFI) were calculated. The WBC group was compared to the kinesiotherapy only (KT; n = 16) group. The routine parameters of oxidative stress (antioxidant enzymatic and nonenzymatic antioxidant status, lipid peroxidation products, total oxidative status (TOS), and oxidative stress index (OSI)) were estimated one day before the beginning and one day after the completion of the research program. Results After the completion of the treatment in the WBC group, a significant decrease of oxidative stress markers (TOS and OSI) and a significant increase of total antioxidant status were observed. The erythrocyte activity of glutathione peroxidase, glutathione reductase decreased significantly in both groups, but the differences of activity of that enzymes prior to post treatment values (Δ) in the KT group were significantly higher as compared to the WBC group. The activity of erythrocyte catalase and plasma ZnCu isoenzyme of superoxide dismutase showed a decreased tendency; erythrocyte total superoxide dismutase activity showed an increased tendency in the WBC group after the completion of the treatment. The BASDAI and BASFI decreased significantly in both groups, but the differences of value indexes prior to post treatment (Δ) were significantly higher in the WBC than KT group. Conclusion WBC performed in a closed cryochamber decreases oxidative stress and improves BASDAI and BASFI indexes in male patients during the active phase of ankylosing spondylitis.
Research Article
Decreased Oxidative Stress in Male Patients with Active
Phase Ankylosing Spondylitis Who Underwent Whole-Body
Cryotherapy in Closed Cryochamber
Agata Stanek ,
1
Armand Cholewka,
2
Tomasz Wielkoszyński ,
3
Ewa Romuk ,
3
and Aleksander Sieroń
1
1
Department of Internal Medicine, Angiology and Physical Medicine, School of Medicine with the Division of Dentistry in Zabrze,
Medical University of Silesia, Batorego Street 15, 41-902 Bytom, Poland
2
Department of Medical Physics, Chelkowski Institute of Physics, University of Silesia, 4 Uniwersytecka St., 40-007 Katowice, Poland
3
Department of Biochemistry, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia, Jordana 19
St., 41-808 Zabrze, Poland
Correspondence should be addressed to Agata Stanek; astanek@tlen.pl
Received 14 January 2018; Accepted 10 April 2018; Published 2 May 2018
Academic Editor: Karolina Szewczyk-Golec
Copyright © 2018 Agata Stanek et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Objective. The aim of the study was to estimate the impact of whole body cryotherapy (WBC) on oxidative stress when performed in
a closed cryochamber on patients with ankylosing spondylitis (AS). Material and methods. The eect of ten WBC procedures
lasting 3 minutes a day with a subsequent 60-minute session kinesiotherapy on oxidative stress in male AS patients (WBC
group n=16) was investigated. To assess the disease activity, the Bath Ankylosing Spondylitis Diseases Activity Index
(BASDAI) and Bath Ankylosing Spondylitis Functional Index (BASFI) were calculated. The WBC group was compared to the
kinesiotherapy only (KT; n=16) group. The routine parameters of oxidative stress (antioxidant enzymatic and nonenzymatic
antioxidant status, lipid peroxidation products, total oxidative status (TOS), and oxidative stress index (OSI)) were estimated
one day before the beginning and one day after the completion of the research program. Results. After the completion of the
treatment in the WBC group, a signicant decrease of oxidative stress markers (TOS and OSI) and a signicant increase of total
antioxidant status were observed. The erythrocyte activity of glutathione peroxidase, glutathione reductase decreased
signicantly in both groups, but the dierences of activity of that enzymes prior to post treatment values (Δ) in the KT group
were signicantly higher as compared to the WBC group. The activity of erythrocyte catalase and plasma ZnCu isoenzyme of
superoxide dismutase showed a decreased tendency; erythrocyte total superoxide dismutase activity showed an increased
tendency in the WBC group after the completion of the treatment. The BASDAI and BASFI decreased signicantly in both
groups, but the dierences of value indexes prior to post treatment (Δ) were signicantly higher in the WBC than KT group.
Conclusion. WBC performed in a closed cryochamber decreases oxidative stress and improves BASDAI and BASFI indexes in
male patients during the active phase of ankylosing spondylitis.
1. Introduction
Ankylosing spondylitis (AS) is a chronic, usually progressive
inammatory rheumatic disease with severe complications
that include sacroiliitis, spondylodesis, peripheral arthritis,
and a range of extra-articular manifestations, ultimately lead-
ing to impacts upon mobility and societal functioning [1].
The pathogenesis of AS is still unknown, but lately it has been
postulated that oxidative stress might be involved in the dis-
ease [26]. Oxidative stress can induce acute or chronic
inammation through the activation of multiple pathways.
When oxidative stress appears as a primary disorder, inam-
mation develops as a secondary disorder and further
enhances oxidative stress [7].
In addition to pharmacological treatment, physiotherapy
plays an important role in the treatment of AS patients. They
Hindawi
Oxidative Medicine and Cellular Longevity
Volume 2018, Article ID 7365490, 9 pages
https://doi.org/10.1155/2018/7365490
are commonly used to maintain spinal mobility, decrease
spinal deformity, and reduce pain as well as improve patients
functioning and quality of life [8, 9].
More and more frequently, whole-body cryotherapy
(WBC), as a method of physical medicine, is used in the treat-
ment of rheumatic and inammatory diseases and muscle
spasticity [10]. During WBC treatment, the subject is exposed
to extreme cold temperatures (below 100
°
C) for a short
period of time (maximum up to 3 minutes) [11, 12]. The
action of cryogenic temperatures causes several favorable
physiological reactions such as an analgesic, anti-inamma-
tory, and a circulatory eect [1215]. Cryogenic temperatures
applied to the whole body, apart from the aforementioned
eects, also have signicant inuence on the psyche, the
immune, and endocrine systems [1518].
However, little is still known about the mechanisms of
WBC treatment in AS patients. So far, it has been showed
that WBC procedures with subsequent kinesiotherapy may
help to decrease pain and inammatory parameters,
improve BASDAI (Bath Ankylosing Spondylitis Diseases
Activity Index) and BASFI (Bath Ankylosing Spondylitis
Functional Index) indexes, and some spinal mobility param-
eters [1921]. It has been also proven that in AS patients,
WBC treatment performed in a cryochamber with cold
retention may decrease oxidative stress and lipid prole
parameters [22].
However, the eect of WBC treatment may depend on
the type of cryochamber in which procedures are performed
[21, 22]. The most popular cryochambers are chambers with
cold retention and closed ones (called Wroclawski type or
two-step cryochamber).
In the cryochamber with cold retention, in order to make
use of the cold depositphenomenon, the cryogenic cham-
ber is placed about 2.5 m under oor level. It is cooled by
synthetic liquid air. The subjects enter the therapy chamber
by stairs which constitute a mild adaptive area. An open ante-
chamber (vestibule) is located at the base of the stairs. The
vestibule and the proper chamber are separated by double
swing doors [23, 24].
The closed Wroclawski-type cryochamber is placed at
oor level. It is usually cooled by liquid nitrogen. The vesti-
bule and the proper chamber are located on the same level
and separated by a lockable door [24].
But until now, there are no papers in available literature
on the impact of WBC treatment performed in a closed cryo-
chamber (Wroclawski type) on oxidative stress in AS patients.
In light of the above ndings, and taking account that
WBC treatment may be performed in dierent types of
cryochambers, the primary aim of the study was to assess
the inuence of WBC performed in a closed cryochamber
(Wroclawski type) on oxidative stress in AS patients during
the active phase.
2. Materials and Methods
2.1. Subjects. The research was conducted with the consent of
the Bioethical Committee of the Medical University of Silesia
in Katowice (permission number NN-6501-93/I/07), Poland.
All examined subjects provided written informed consent.
All investigations were conducted according to the principles
expressed in the Declaration of Helsinki (1964).
The research involved a group of 32 nonsmoking male
patients with ankylosing spondylitis who were divided ran-
domly by a physician into two groups with an allocation
ratio 1 : 1. The rst group consisted of 16 AS patients
exposed to whole-body cryotherapy procedures with subse-
quent kinesiotherapy (WBC group, mean age 46.63 ±1.5
years). The second group consisted of 16 AS patients exposed
only to kinesiotherapy procedures (KT group, mean age
45.94 ±1.24 years). There was no signicant dierence in
the mean age, BMI, BASDAI, BASFI, and treatment between
these groups.
Male patients who were successfully enrolled in the
research had a denite diagnosis of AS, did not suer from
any other diseases, had no associated pathologies, and had
no treatment with disease-modifying antirheumatic drugs
(DMARDs), biologic agents, or steroids. The AS patients
were treated with doses of nonsteroidal anti-inammatory
drugs (NSAIDs), which were not altered within one month
before the beginning of the study and during it. All the
patients included in the trial fullled the modied New York
Criteria for denite diagnosis of AS, which serves as the basis
for the ASAS/EULAR recommendations [25]. The nal
selection for the study included only HLA B27 positive
patients, who exhibited II and III radiographic grades of
sacroiliac joint disease and attended a consulting unit in a
health resort in the period of subsidence of acute clinical
symptoms, in order to qualify for physiotherapy treatment.
The demographic characteristics of the subjects is shown in
Table 1.
Before the research, each patient was examined by a
physician to exclude any coexisting diseases as well as any
contraindications for WBC procedures. Prior to the research,
a resting electrocardiogram was performed in all the patients,
and before each session of WBC, the blood pressure was
measured for each patient [24].
The patients from both groups were asked to abstain
from alcohol, drugs, and any immunomodulators, immu-
nostimulators, hormones, vitamins, minerals, or other sub-
stances with antioxidant properties for 4 weeks before the
study. All the patients were also asked to refrain from the
consumption of caeine 12 hours prior to laboratory analy-
ses. The diet of the patients was not modied.
2.2. Scheme of Whole-Body Cryotherapy and Kinesiotherapy
Procedures. Depending on the group, the AS patients were
exposed either to a cycle of WBC procedures lasting 3
minutes a day with a subsequent 60-minute session of
kinesiotherapy or 60-minute session of kinesiotherapy only
for 10 consecutive days excluding the weekend at the same
time in the morning.
The WBC procedures were performed in a cryochamber
Wroclawski type (closed cryochamber) cooled by liquid
nitrogen (produced by Creator, Poland), which consisted of
separated two compartments: the antechamber (vestibule)
and the proper chamber. The temperature in the antechamber
was 60
°
C, whereas in the proper chamber, it reached 120
°
C.
The subjects entered the chamber in groups of four. Each
2 Oxidative Medicine and Cellular Longevity
entry to the cryochamber was preceded by a 30-second adap-
tation period in the vestibule at 60
°
C. After adaptation, the
subjects stepped into the proper chamber, where they were
exposed to cryogenic temperatures for 3 minutes. During
the WBC procedure, all the patients were dressed in swim-
suits, they wore cotton socks and gloves and wooden shoes,
and their mouths and noses were protected by dust masks
and their ears by ear-protectors. No jewelry, glasses, and
contact lenses were allowed. Each subject was informed
about the rules: the need for slow, shallow breathing (short
nasal inhalation and longer oral exhalation), and the way
to move about (slow walking in circles, one after the other).
During the WBC procedure, they were also not allowed to
touch each other.
Immediately after leaving the cryogenic chamber, the AS
patients underwent kinesiotherapy lasting for one hour. The
program of kinesiotherapy was the same for all the patients in
both groups. Kinesiotherapy procedures included range-of-
motion exercises of the spine and major joints (including
the hip, knee, ankle, shoulder, elbow, and wrist). Chest
expansion and breathing exercises were also included. Apart
from range-of-motion exercise, the AS patients received
strengthening exercises of the muscles of the major body
parts (spine, arms, and thighs) as well as aerobic exercise
(including cycling and fast walking). All the exercises were
carried out under the supervision of physiotherapists [22].
All the patients completed the research program and no
complications or side eects related to the WBC procedures
were observed.
2.3. Blood Sample Collection. Blood samples of all the subjects
were collected in the morning before the rst meal one day
before the beginning and one day after the completion of the
research program. Samples of whole blood (5 ml) were drawn
from the basilic vein and then collected into tubes containing
ethylenediaminetetraacetic acid (Sarstedt, S-Monovette with
1.6 mg/ml EDTA-K
3
) and into tubes with a clot activator
(Sarstedt, S-Monovette). The blood samples were centrifuged
(10 min., 900g4
°
C) and then the plasma and serum
were immediately separated and stored at the temperature
of 75
°
C, until biochemical analyses could be performed.
The red blood cells retained from the removal of EDTA
plasma were rinsed with isotonic salt solution, and then 10%
of the hemolysates were prepared for further analyses. The
hemoglobin concentration in the hemolysates was deter-
mined by the standard cyanmethemoglobin method. The
inter- and intra-assay coecients of variations (CV) were
1.1% and 2.4%, respectively.
2.4. Biochemical Analysis
2.4.1. Oxidative Stress Analysis
(1) Determination of Activity of Antioxidant Enzymes. The
plasma and erythrocytes superoxide dismutase (SOD-
E.C.1.15.1.1) activity was assayed by the Oyanagui method
[26]. Enzymatic activity was expressed in nitrite unit (NU)
in each mg of hemoglobin (Hb) or ml of blood plasma.
One nitrite unit (1 NU) means a 50% inhibition of nitrite
ion production by SOD in this method. SOD isoenzymes
(SOD-Mn and SOD-ZnCu) were measured using potassium
cyanide as the inhibitor of the SOD-ZnCu isoenzyme. The
inter- and intra-assay coecients of variations (CV) were
2.8% and 5.4%, respectively.
The catalase (CAT-E.C.1.11.1.6.) activity in erythrocytes
was measured by the Aebi [27] kinetic method and expressed
in [IU/mgHb]. The inter- and intra-assay coecients of
variations (CV) were 2.6% and 6.1%, respectively.
The activity of erythrocyte glutathione peroxidase (GPx-
E.C.1.11.1.9.) was assayed by Paglia and Valentines kinetic
method [28], with t-butyl peroxide as a substrate and
expressed as micromoles of NADPH oxidized per minute
and normalized to one gram of hemoglobin [IU/gHb]. The
inter- and intra-assay coecients of variations (CV) were
3.4% and 7.5%, respectively.
The glutathione reductase in erythrocytes (GR-
E.C.1.6.4.2) activity was assayed by Richterichs kinetic
method [29], expressed as micromoles of NADPH utilized
per minute and normalized to one gram of hemoglobin
[IU/g Hb]. The inter- and intra-assay coecients of varia-
tions (CV) were 2.1% and 5.8%, respectively.
Table 1: Demographic characteristics of the research subjects.
Characteristic WBC group
(n=16)
Kinesiotherapy group
(n=16)pvalue
Age, years, mean (SD) 46.63 ±1.5 45.94 ±1.24 0.114
Sex M/F 16/0 16/0
BMI, kg/m
2
, mean (SD) 24.35 ±4.4 23.76 ±6.8 0.968
BASDAI 5.34 ±1.72 5.28 ±1.71 0.880
BASFI 5.17 ±2.28 5.01 ±2.06 0.940
Smoking (yes/no) 0/16 0/16
Medication
NSAID (yes/no) 16/0 16/0
DMARD (yes/no) 0/16 0/16
Biological agents (yes/no) 0/16 0/16
SD: standard deviation; BMI: body mass index; BASDAI: the Bath Ankylosing Spondylitis Diseases Activity Index; BASFI: the Bath Ankylosing Spondylitis
Functional Index; NSAID: nonsteroidal anti-inammatory drug; DMARD: disease-modifying antirheumatic drug.
3Oxidative Medicine and Cellular Longevity
(2) Determination of Nonenzymatic Antioxidant Status. The
total antioxidant capacity of plasma was measured as the fer-
ric reducing ability of plasma (FRAP) according to Benzie
and Strain [30] and calibrated using Trolox and expressed
in [μmol/l]. The inter- and intra-assay coecients of varia-
tions (CV) were 1.1% and 3.8%, respectively.
The serum concentration of protein sulfhydryl (PSH)
was measured by Koster et al.s method [31] using dithioni-
trobenzoic acid (DTNB) and expressed in [μmol/l]. The
inter- and intra-assay coecients of variations (CV) were
2.6% and 5.4%, respectively.
The serum concentration of uric acid (UA) was assayed
by a uricase-peroxidase method [32] on the Cobas Integra
400 plus analyzer and expressed as [mg/dl]. The inter- and
intra-assay coecients of variations (CV) were 1.4% and
4.4%, respectively.
(3) Determination of Lipid Peroxidation Products, Total
Oxidatative Status, and Oxidative Stress Index. The intensity
of lipid peroxidation in the plasma and the erythrocytes was
measured spectrouorimetrically as thiobarbituric acid-
reactive substances (TBARS) according to Ohkawa et al.
[33]. The TBARS concentrations were expressed as malon-
dialdehyde (MDA) equivalents in [μmol/l] in plasma or
[nmol/gHb] in erythrocytes. The inter- and intra-assay coef-
cients of variations (CV) were 2.1% and 8.3%, respectively.
The serum total oxidant status (TOS) was determined
with the method described by Erel [34] and expressed in
[μmol/l]. The inter- and intra-assay coecients of variations
(CV) were 2.2% and 6.4%, respectively.
The oxidative stress index (OSI), an indicator of the
degree of oxidative stress, was expressed as the ratio of total
oxidant status (TOS) to total antioxidant capacity (FRAP)
in arbitrary units [35].
2.5. Assessment of Activity of Ankylosing Spondylitis. The
activity of ankylosing spondylitis was measured by the Bath
Ankylosing Spondylitis Diseases Activity Index (BAS-
DAI) and the Bath Ankylosing Spondylitis Functional
Index (BASFI).
The BASDAI has six questions related to fatigue, back
pain, peripheral pain, peripheral swelling, local tenderness,
and morning stiness (degree and length). Other than the
issues relating to morning stiness, all questions were scored
from 0 (none) to 10 (very severe) using a visual analogue
scale (VAS). The sum was calculated as the mean of two
morning stiness issues and the four remaining issues [36].
The BASFI is the mean score of ten questions addressing
functional limitations and the level of physical activity at
home and work, assessed on VAS scales (0 = easy,
10 = impossible) [37].
2.6. Statistical Analysis. For statistical analysis, the statistical
package of Statistica 10 Pl software was used. For each
parameter, the indicators of the descriptive statistics were
determined (mean value and standard deviation SD). The
normality of the data distribution was checked using the
ShapiroWilk test, while the homogeneity of the variance
was checked by applying the Levenes test. In order to
compare the dierences between the groups, an independent
sample Student t-test was used or alternatively the
MannWhitney Utest. In the case of dependent samples,
the Student t-test was used or alternatively the Wilcoxon
test. Dierences at the signicance level of p<0 05 were
considered as statistically signicant.
3. Results
3.1. Antioxidants Enzymes. AS patients in the WBC group
had, after the completion of treatment, a statistically signif-
icant decrease in the erythrocyte activity of GPx (20.6 ±5.07
and 18.3 ±4.15 [IU/gHb]before and after therapy,
respectively, p=0002) and GR (1.21 ±0.29 and 0.93 ±0.37
[IU/gHb] [IU/gHb]before and after therapy, respectively,
p=0007). The erythrocyte activity of CAT (423.0 ±61.6
and 380.0 ±102.0 [IU/mgHb]before and after therapy,
respectively, p=0 079) and plasma SOD-CuZn (7.05 ±1.92
and 5.76 ±2.36 [NU/ml]before and after therapy,
respectively, p=0063) showed a decreased tendency. The
erythrocyte activity of total SOD (104.0 ±15.0 and 112.0 ±
11.2 [NU/mgHb]before and after therapy, respectively,
p=0056) showed an increased tendency.
However, the activity of plasma total SOD (12.4 ±1.89
and 11.5 ±3.19 [NU/ml]before and after therapy, respec-
tively, p=0501) and SOD-Mn (5.31 ±1.03 and 6.32 ±2.16
[NU/ml]before and after therapy, respectively, p=0 098)
did not change signicantly in the WBC group after treat-
ment. Similarly, as in the WBC group, the activity of plasma
total SOD (12.3 ±1.85 and 11.7 ±2.49 [NU/ml]before
and after therapy, respectively, p=0301) and SOD-Mn
(4.56 ±1.86 and 5.02 ±1.64 [NU/ml]before and after
therapy, respectively, p=0 642) did not change signicantly
in the KT group after treatment. In the KT group, the
erythrocyte activity of total SOD (128.0 ±11.2 and
111.0 ±15.6 [NU/mgHb]before and after therapy,
respectively, p=0001), GPx (29.9 ±2.84 and 20.4 ±5.05
[IU/gHb]before and after therapy, respectively, p=0 001)
and GR (2.07 ±0.52 and 1.65 ±0.59 [IU/gHb]before and
after therapy, respectively, p=0 002), similar to the WBC
group of patients, decreased signicantly after treatment.
Additionally, the dierences of activity of erythrocyte total
SOD (17.1 ±11.8 [NU/mgHb] in the KT group versus
7.77 ±17.2 [NU/mgHb] in the WBC group, p<0 001) and
GPx (9.49 ±6.74 [IU/gHb] in the KT group versus 2.27 ±
1.98 [IU/gHb] in the WBC group, p=0 001) prior to post-
treatment values (Δ) in the KT group were signicantly higher
as compared to the WBC group. In the KT group, the activity
of erythrocyte CAT (425.0 ±53.6 and 412.0 ±58.6
[IU/mgHb]before and after therapy, respectively, p=0352)
and plasma SOD-CuZn (7.80 ±2.21 and 7.05 ±3.09
[NU/ml]before and after therapy, respectively, p=0 326)
did not change signicantly after treatment in comparison
to the WBC group (Table 2).
3.2. Nonenzymatic Antioxidant Status. In the WBC group
FRAP values (514.1 ±63.2 and 587.9 ±50.9 [μmol/l]before
and after therapy, respectively, p=0 001) increased signi-
cantly after treatment. The UA level showed an increased
4 Oxidative Medicine and Cellular Longevity
tendency in WBC group of patients (4.44 ±1.43 and
4.75 ±1.08 [mg/dl]before and after therapy, respectively,
p=0066). After completion of the treatment FRAP values
were signicantly higher in the WBC group (587.9 ±50.9
[μmol/l] when compared to the KT group (499.3 ±74.6
[μmol/l]) (p=0001). The level of PSH (627.6 ±248.0 and
616.5 ±279.1 [μmol/l]before and after therapy, respec-
tively, p=0918) in the WBC group of patients did not
change signicantly after treatment. In turn, FRP values
(550.0 ±91.3 and 499.3 ±74.6 [μmol/l]before and after
therapy, respectively, p=0 001) and PSH concentration
(393.2 ±90.0 and 364.7 ±28.4 [μmol/l]before and after
therapy, respectively, p=0017) decreased signicantly, in
the KT group, but the level of UA (4.34 ±1.15 and
4.61 ±1.25 [mg/dl]before and after therapy, respectively,
p=0196) did not change signicantly after treatment
(Table 3).
3.3. Lipid Peroxidation Products, Total Oxidative Status, and
Oxidative Stress Index. AS patients in the WBC group
had, after the completion of the treatment, a statistically
signicant decrease in serum TOS (30.49 ±13.35 and
14.56 ±9.01[μmol/l]before and after therapy, respectively,
p=0003) and value of OSI index (64.19 ±65.93 and 10.20 ±
3.79before and after therapy, respectively, p=0 001)in
comparison to initial values. The dierences of these
parameters prior to posttreatment values in the WBC group
were signicantly higher in comparison to the KT group
(ΔTOS 15.93 ±17.04 [μmol/l] in the WBC group versus
0.46 ±9.11[μmol/l] in the KT group, p=0 003;ΔOSI
53.99 ±66.83 in WBC group versus 4.78 ±13.88 in the
KT group, p=0003). The levels of MDA in plasma
(2.66 ±0.73 and 2.48 ±0.57 [μmol/l]before and after
therapy, respectively, p=0 215) and in erythrocyte (0.16 ±
0.01 and 0.15 ±0.02 [nmol/gHb]before and after therapy,
respectively, p=0 098) did not change signicantly in the
WBC group. In the KT group, no signicant changes in
the levels of plasma MDA (2.32 ±0.60 and 2.41 ±0.83
[μmol/l]before and after therapy, respectively, p=0 959)
and erythrocyte MDA (0.18 ±0.02 and 0.18 ±0.04 [nmol/
gHb]before and after therapy, p=0 642) as well as serum
TOS (23.94 ±11.60 and 24.41 ±6.24 [μmol/l]before and
after therapy, respectively, p=0 605) and OSI index
(18.87 ±11.30 and 23.65 ±15.68before and after therapy,
respectively, p=0301) were observed after the completion
of treatment, in comparison to the initial values before the
beginning of the kinesiotherapy cycle (Table 4).
Table 2: Activities of antioxidant enzymes (mean value ±standard
deviation SD) in AS patients before and after the completion of a
cycle of ten whole-body cryotherapy procedures with subsequent
kinesiotherapy (WBC group) or a cycle of ten kinesiotherapy
procedures only (KT group), with statistical analyses. (p): plasma;
(e): erythrocyte lysates; Δ:dierence prior to post treatment.
Parameters WBC group KT group p
Total SOD (p)
[NU/ml]
Before 12.4 ±1.89 12.3 ±1.85 0.927
After 11.5 ±3.19 11.7 ±2.49 0.884
P0.501 0.301
Δ0.81 ±3.08 0.60 ±2.65 0.837
SOD-Mn (p)
[NU/ml]
Before 5.31 ±1.03 4.56 ±1.86 0.170
After 6.32 ±2.16 5.02 ±1.64 0.066
P0.098 0.642
Δ1.01 ±2.15 0.46 ±2.46 0.509
SOD-CuZn (p)
[NU/ml]
Before 7.05 ±1.92 7.80 ±2.21 0.310
After 5.76 ±2.36 7.05 ±3.09 0.194
P0.063 0.326
Δ1.29 ±2.46 0.75 ±2.72 0.166
Total SOD (e)
[NU/mgHb]
Before 104.0 ±15.0 128.0 ±11.2 <0.001
After 112.0 ±11.2 111.0 ±15.6 0.759
P0.056 0.001
Δ7.77 ±17.2 17.1 ±11.8 <0.001
CAT (e)
[IU/mgHb]
Before 423.0 ±61.6 425.0 ±53.6 0.914
After 380.0 ±102.0 412.0 ±58.6 0.294
P0.079 0.352
Δ42.3 ±109.0 13.0 ±54.0 0.347
GPx (e)
[IU/gHb]
Before 20.6 ±5.07 29.9 ±2.84 <0.001
After 18.3 ±4.15 20.4 ±5.05 0.207
P0.002 0.001
Δ2.27 ±1.98 9.49 ±6.74 0.001
GR (e)
[IU/gHb]
Before 1.21 ±0.29 2.07 ±0.52 <0.001
After 0.93 ±0.37 1.65 ±0.59 <0.001
P0.007 0.002
Δ0.28 ±0.34 0.42 ±0.41 0.275
P: statistical signicance of dierences between both groups of patients;
P: statistical signicance of dierences between values before and after
treatment in particular groups of subjects.
Table 3: Levels of nonenzymatic antioxidants (mean value ±
standard deviation SD) in AS patients before and after the
completion of a cycle of ten whole-body cryotherapy procedures
with subsequent kinesiotherapy (WBC group) or a cycle of ten
kinesiotherapy procedures only (KT group), with statistical
analyses. (p): plasma; (s): serum; Δ:dierenceprior to post treatment.
Parameters WBC group KT group p
FRAP
[μmol/l
Before 514.1 ±63.2 550.0 ±91.3 0.206
After 587.9 ±50.9 499.3 ±74.6 0.001
P0.001 0.001
Δ73.9 ±55.0 50.8 ±39.4 <0.001
PSH (s)
[μmol/l]
Before 627.6 ±248.0 393.2 ±90.0 0.772
After 616.5 ±279.1 364.7 ±28.4 0.239
P0.918 0.017
Δ11.1 ±281.7 28.5 ±92.6 0.605
UA (s)
[mg/dl]
Before 4.44 ±1.43 4.34 ±1.15 0.838
After 4.75 ±1.08 4.61 ±1.25 0.738
P0.066 0.196
Δ0.31 ±1.02 0.27 ±0.70 0.885
P: statistical signicance of dierences between both groups of patients;
P: statistical signicance of dierences between values before and after
treatment in particular groups of patients.
5Oxidative Medicine and Cellular Longevity
3.4. BASDAI and BASFI Indexes. The BASDAI (5.34 ±1.72
and 3.19 ±0.91 in the WBC groupbefore and after therapy,
respectively, p=0001; 5.28 ±1.71 and 4.53 ±1.62 in the KT
groupbefore and after therapy, respectively, p<0 001)
and BASFI (5.17 ±2.28 and 3.79 ±2.21 in the WBC
groupbefore and after therapy, respectively, p<0 001;
5.01 ±2.06 and 4.35 ±2.23 in the KT groupbefore and after
therapy, respectively, p<0001) indexes decreased signi-
cantly in both groups, but in the WBC group, with subse-
quent kinesiotherapy after the completion of the treatment,
the decrease of these parameters was signicantly higher in
comparison to the KT group (ΔBASDAI 2.16 ±1.29 in the
WBC group versus 0.74 ±0.38 in the KT group, p<0 001;
ΔBASFI 1.38 ±1.07 in the WBC group versus 0.66 ±0.39
in the KT group, p=0 007). The value of both BASDAI
and BASFI indexes was below 4 (inactive phase of AS
disease) only in the WBC group after the completion of
treatment (Table 5).
4. Discussion
After the completion of the treatment, a signicant decrease
in markers of oxidative stress was achieved in the WBC
group of AS patients who underwent a ten-day long cycle
of WBC procedures with subsequent kinesiotherapy. In that
group of patients, a signicant decrease in levels of TOS
and OSI values as well as in activity of erythrocyte GPx and
GR was observed. A decreased tendency was also noticed in
the activity of plasma SOD-CuZn and erythrocyte CAT.
Contrary, an increased tendency was seen in the activity of
erythrocyte total SOD and the level of UA after the comple-
tion of treatment in the WBC group. The FRAP value was
increased signicantly after the completion of treatment in
the WBC group. No signicant changes were noted in the
activity of plasma total SOD and SOD-Mn, as well as levels
of PSH and both plasma and erythrocyte MDA after the
completion of treatment in the WBC group.
These ndings are similar to our previous research, in
which a benecial impact on oxidative stress from ten
WBC procedures performed in a cryochamber with cold
retention (temperature: 120
°
C, time: 3 min, liquid air cool-
ant) both in healthy subjects and AS patients was observed
[22, 38]. It has been suggested by Mila-Kierzenkowska et al.
[23] that even a single application of cryotherapy prior to
exercise may have a benecial impact on antioxidant system
of organism and alleviate the signs of exercise-induced oxida-
tive stress (a single session of WBC, temperature: 130
°
C,
time: 1-2 min., cryochamber with cold retention, liquid
air coolant).
However, it has been shown by Lubkowska et al. [39]
that a single session of WBC (temperature: 130
°
C, time:
3 minutes, two-step cryochamber, liquid nitrogen coolant)
could induce disturbances in prooxidant-antioxidant bal-
ance, in the form of lowering TOS and a temporary
decrease in TAS, with a subsequent elevation of those param-
eters on the following day, resulting in an intensication of
oxidative stress.
In another study by the same team [39], healthy men
have been exposed to a single WBC session (temperature:
130
°
C, time 3 minutes, two-step cryochamber, liquid nitro-
gen coolant) without subsequent kinesiotherapy. A signi-
cant increase in GPx and GR activities, with a simultaneous
decrease in CAT and glutathione S-transferase activities,
was observed. A signicant increase in the concentration
Table 4: Levels of lipid peroxidation parameters, total oxidative
status (TOS), and oxidative stress (OSI) index (mean value
±standard deviation SD) in AS patients before and after the
completion of a cycle of ten whole-body cryotherapy procedures
with subsequent kinesiotherapy (WBC group) or a cycle of ten
kinesiotherapy procedures only (KT group), with statistical
analyses. (p): plasma; (s): serum; (e): erythrocyte lysates; Δ:
dierence prior to post treatment.
Parameters WBC group KT group p
MDA (p)
[μmol/l]
Before 2.66 ±0.73 2.32 ±0.60 0.157
After 2.48 ±0.57 2.41 ±0.83 0.783
P0.215 0.959
Δ0.19 ±0.72 0.09 ±1.04 0.391
MDA (e)
[nmol/gHb]
Before 0.16 ±0.01 0.18 ±0.02 0.001
After 0.15 ±0.02 0.18 ±0.04 0.001
P0.098 0.642
Δ0.01 ±0.03 0.00 ±0.04 0.155
TOS (s)
[μmol/l]
Before 30.49 ±13.35 23.94 ±11.60 0.149
After 14.56 ±9.01 24.41 ±6.24 0.001
P0.003 0.605
Δ15.93 ±17.04 0.46 ±9.11 0.003
OSI (p/s)
[arbitrary unit]
Before 64.19 ±65.93 18.87 ±11.30 0.016
After 10.20 ±3.79 23.65 ±15.68 0.004
P0.001 0.301
Δ53.99 ±66.83 4.78 ±13.88 0.003
P: statistical signicance of dierences between both groups of patients;
P: statistical signicance of dierences between values before and after
treatment in particular groups of patients.
Table 5: The value of BASDAI and BASFI indexes (mean value ±
standard deviation SD) in AS patients before and after the
completion of a cycle of ten whole-body cryotherapy procedures
with subsequent kinesiotherapy (WBC group) or a cycle of ten
kinesiotherapy procedures only (KT group), with statistical
analyses. (p): plasma; (s): serum; Δ:dierenceprior to post treatment.
Parameters WBC group KT group p
BASDAI index
Before 5.34 ±1.72 5.28 ±1.71 0.880
After 3.19 ±0.91 4.53 ±1.62 0.030
P0.001 <0.001
Δ2.16 ±1.29 0.74 ±0.38 0.001
BASFI index
Before 5.17 ±2.28 5.01 ±2.06 0.940
After 3.79 ±2.21 4.35 ±2.23 0.406
P<0.001 <0.001
Δ1.38 ±1.07 0.66 ±0.39 0.007
P: statistical signicance of dierences between both groups of patients;
P: statistical signicance of dierences between values before and after
treatment in particular groups of patients.
6 Oxidative Medicine and Cellular Longevity
of glutathione, uric acid, albumins, and extra-erythrocyte
hemoglobin was also observed in the serum of the subjects.
It was concluded by the authors that a single stimulation
with cryogenic temperatures results in oxidative stress in a
healthy body, but the level of this stress is not very high.
It has been suggested that repeated exposure to cryogenic
temperatures may cause adaptative changes in the form of an
increase in antioxidant status and antioxidant enzyme activ-
ity, resulting in the formation of a prooxidant-antioxidant
balance at a higher level (according to hormesis theory) [40].
A benecial impact of WBC on prooxidant-antioxidant
balance has been observed in both male and female kayak ath-
letes when WBC procedures were included into the training
regime [40, 41]. The increase in total antioxidant status and
the level of UA as a result of a series of short-term whole-
body cryotherapy (10 WBC sessions, temperature: 130
°
C,
time: 3 minutes, without subsequent kinesiotherapy) has been
also observed by Miller et al. [42] in healthy subjects. How-
ever, in other study [43], the authors have shown that the
activity of antioxidant enzymes in healthy men depends on
the number of WBC procedures (temperature: 130
°
C, time:
3 minutes). It was also suggested that WBC intensies oxida-
tive stress and causes an accompanying decrease in antioxi-
dant enzyme activity after 10 sessions, with a subsequent
compensatory increase after the completion of a cycle of 20
sessions. In a dierent study [44], patients with seropositive
rheumatoid were observed by the authors to have only a
short-term increase in TRAP during the rst treatment ses-
sion of WBC (the temperature110
°
C, three times daily for
7 consecutive days), and no signicant oxidative stress or
adaptation were caused by the cold treatment.
In our research a signicant decrease in BASDAI and
BASFI indexes in the WBC group after the completion of
treatment was observed. These results are similar to our pre-
vious research, in which WBC procedures were performed in
a cryochamber with cold retention and two-step cryocham-
ber (Wroclawski type) [19, 22]. In both studies, after the
completion of a cycle of WBC procedures consisting of ten
3 minute long WBC procedures daily with subsequent kine-
siotherapy (temperature120
°
C, time 3 min, 10 sessions with
a weekend break), a decreased of the BASDAI and BASFI
index below 4 was observed, which suggests that the AS
disease turned into an inactive phase after the completion
of treatment. Similar results in AS patients have also been
observed by Romanowski et al. [20] (8 daily WBC proce-
dures, the temperature 110
°
C, time 3 min).
The dierences in the results of various studies may be
related to the type of cryochamber being used and the coolant
medium, in addition to the time of exposure to cryogenic
temperatures. Further studies are necessary to estimate
whether the number of WBC procedures and type of cryo-
chamber may have an inuence on prooxidant-antioxidant
balance in subjects who underwent WBC treatment. Compa-
rability of the results obtained by dierent research teams
could be improved through standardization of exposure
times and the number of treatments during each cycle. In
an attempt to optimise treatment, sexually dimorphism, body
fat percentage, and BMI dierences should be also taken into
account [45, 46].
The present study has some limitations. Firstly, the study
did not provide long-term follow-up (at least 3 months), and
thus we are not sure how long the benecial eect of WBC
with subsequent kinesiotherapy would be maintained after
the completion of a WBC cycle. Secondly, the cycle of
WBC with subsequent kinesiotherapy consisted of ten proce-
dures only. A greater number of procedures (e.g., 2030)
could probably intensify the treatment eect. Thirdly,
the next studies should involve a larger number of AS
patients in dierent stages of the disease. Females should be
also included.
5. General Conclusion
Whole-body cryotherapy procedures performed in a closed
cryochamber (Wroclawski type) with subsequent kine-
siotherapy decrease oxidative stress as well as BASDAI and
BASFI indexes in AS patients during the active phase of
the disease.
Data Availability
All data are included in the tables within the article.
Conflicts of Interest
The authors declare that there are no conicts of interests
regarding the publication of this paper.
Acknowledgments
This work was supported by a grant from the Medical
University of Silesia (KNW-1-045/K/7/K).
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9Oxidative Medicine and Cellular Longevity
... Oxidative stress can be a pathologic hallmark of autoimmune diseases, leading to more inflammation and adding to the constant pain a patient is in [21]. Studies have shown that cryotherapy may reduce oxidative stress by increasing total antioxidant status (TAS) [22,23] and ferric reducing ability of plasma (FRAP), which is another way of measuring overall antioxidant status [24]. Additionally, research suggests that cryotherapy decreases total oxidant status (TOS) and oxidative status index (OSI), which is a ratio of TOS to TAS, as well [22,24,25]. ...
... Studies have shown that cryotherapy may reduce oxidative stress by increasing total antioxidant status (TAS) [22,23] and ferric reducing ability of plasma (FRAP), which is another way of measuring overall antioxidant status [24]. Additionally, research suggests that cryotherapy decreases total oxidant status (TOS) and oxidative status index (OSI), which is a ratio of TOS to TAS, as well [22,24,25]. ...
... Stanek et al. reported in two different studies a significantly reduced mean pain (VAS) score following WBC at -120°C and rehab, along with a significantly greater reduction compared to the control group with just rehab [28,31]. Stanek et al. also reported in two additional studies a significant decrease in disease activity as measured by BASDAI, and the WBC (-120°C) and rehab groups had a significantly greater reduction in BASDAI than the control groups that just received rehab [24,32]. A decrease in BASDAI was also reported by Straburzynska-Lupa et al. in all their study groups (WBC at Randomized RA None reported -110°C ? ...
Article
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Background Cryotherapy has been used to reduce chronic pain for many years due in part to its ease of use, affordability, and simplicity. It can be applied either locally (e.g., ice packs) or non-locally (e.g., partial and whole-body cryotherapy) depending on the location of the pain.Objectives To determine the overall effectiveness of cryotherapy at reducing chronic pain by characterizing the currently available evidence supporting the use and effects of cryotherapy on chronic pain associated with chronic diseases.Study DesignA narrative review of original research studies assessing the efficacy of cryotherapy in alleviating chronic pain.MethodsA PubMed database search was performed to find human studies between the years 2000 and 2020 that included the application of cryotherapy in patients with chronic pain associated with chronic diseases. A review of the relevant references was also performed to gather more articles. Data was extracted, summarized into tables, and qualitatively analyzed.ResultsTwenty-five studies (22 randomized controlled trials, one prospective analysis, 1 one-group pretest/posttest study, and one case–control study) were included after the literature search. Both local and non-local cryotherapy applications show promise in reducing chronic pain associated with various chronic diseases including those of rheumatic and degenerative origin. Cryotherapy appears to be a safe therapy in carefully selected patients, with only minimal adverse effects reported in the literature.LimitationsMeta-analysis was not possible given the many differences between studies. Cross-study data homogenization and comparison between studies proved fairly difficult due to the lack of standardized studies, various uses and practice types of cryotherapy, and lack of control groups in some studies.Conclusions Local and non-local cryotherapy can be low-risk and easy treatment options to add in the management of chronic pain in carefully selected patients. However, long-term effects, a standardized approach, and careful study of other chronic pain syndromes should be considered in future research to further support the use of cryotherapy in the management of chronic pain.
... iNOS activation may be the reason for the intensification of nitro-oxidative stress [34], although WBC treatments show an antioxidant effect [17][18][19]. Increasing the antioxidant defence as a result of WBC may reduce the level of the superoxide radical anion and the protective effects of increasing the bioavailability of NO as a result of the increased concentration of iNOS found after the treatments. A reduction in oxidative stress has been shown in both healthy individuals [19,37] and patients with ankylosing spondylitis [18] undergoing systemic cryotherapy followed by kinesiotherapy. ...
... Increasing the antioxidant defence as a result of WBC may reduce the level of the superoxide radical anion and the protective effects of increasing the bioavailability of NO as a result of the increased concentration of iNOS found after the treatments. A reduction in oxidative stress has been shown in both healthy individuals [19,37] and patients with ankylosing spondylitis [18] undergoing systemic cryotherapy followed by kinesiotherapy. After 10 WBC treatments combined with exercise, a significant reduction in total oxidative status and the oxidative stress index was observed in both groups, as well as a significant increase in the total antioxidant capacity of the blood [18,19]. ...
... A reduction in oxidative stress has been shown in both healthy individuals [19,37] and patients with ankylosing spondylitis [18] undergoing systemic cryotherapy followed by kinesiotherapy. After 10 WBC treatments combined with exercise, a significant reduction in total oxidative status and the oxidative stress index was observed in both groups, as well as a significant increase in the total antioxidant capacity of the blood [18,19]. In healthy men, an increase in the activity of superoxide dismutase in plasma and erythrocytes was also found [19], as well as a decrease in the activity of paraoxonase-1 [37]. ...
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Aging causes oxidative stress, endothelial dysfunction and a reduction in the bioavailability of nitric oxide. The study aim was to determine whether, as a result of repeated whole-body exposure to cryogenic temperature (3 min −130 °C), there is an increase of inducible nitric oxide synthase (iNOS) concentration in senior subjects (59 ± 6 years), and if this effect is stronger in athletes. In 10 long-distance runners (RUN) and 10 untraining (UTR) men, 24 whole-body cryotherapy (WBC) procedures were performed. Prior to WBC, after 12th and 24th treatments and 7 days later, the concentration of iNOS, asymmetric dimethylarginine (ADMA), 3-nitrotyrosine (3-NTR), homocysteine (HCY), C-reactive protein (CRP) and interleukins such as: IL-6, IL-1β, IL-10 were measured. In the RUN and UTR groups, after 24 WBC, iNOS concentration was found to be comparable and significantly higher (F = 5.95, p < 0.01) (large clinical effect size) compared to before 1st WBC and after 12th WBC sessions. There were no changes in the concentration of the remaining markers as a result of WBC (p > 0.05). As a result of applying 24 WBC treatments, using the every-other-day model, iNOS concentration increased in the group of older men, regardless of their physical activity level. Along with this increase, there were no changes in nitro-oxidative stress or inflammation marker levels.
... In this research we used the scheme of WBC and kinesiotherapy procedures developed and presented in our earlier works [8,15,19]. The WBC group was exposed to a cycle of WBC procedures with a subsequent session of kinesiotherapy, while, the KT group was subjected to a session of kinesiotherapy only. ...
... When the WBC procedure was finished, subjects left the proper chamber and went back to the antechamber. Then, after the doors were closed, they left the antechamber one by one [8,15,24]. ...
... It consisted of exercises on stationary bikes lasting 20 min (5 min,3 rate of perceived exertion (RPE); 4 min, 5 RPE; 2 min, 7 RPE; 4 min, 5 RPE; and 5 min, 3 RPE), treadmill (20 min walking at 4.0 mph), and whole-body stretching exercises lasting 20 min. All the exercises were carried out under the supervision of physiotherapists [8,15,19]. All the subjects completed the studies. ...
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Background: The purpose of this study was to estimate the effect of whole-body cryostimulation (WBC) and subsequent kinesiotherapy on inflammatory endothelium and oxidative stress parameters in healthy subjects. Methods: The effects of ten WBC procedures lasting 3 min per day and followed by a 60-min session of kinesiotherapy on oxidative stress and inflammatory endothelium parameters in healthy subjects (WBC group n = 32) were analyzed. The WBC group was compared to a kinesiotherapy only (KT; n = 16) group. The following parameters were estimated one day before the start, and one day after the completion of the studies: oxidative stress parameters (the total antioxidant capacity of plasma (FRAP), paraoxonase-1 activity (PON-1), and total oxidative status (TOS)) and inflammatory endothelium parameters (myeloperoxidase activity (MPO), serum amyloid A (SAA), and sCD40L levels). Results: A significant decrease of PON-1 and MPO activities and TOS, SAA, and sCD40L levels as well as a significant FRAP increase were observed in the WBC group after the treatment. In addition, the SAA levels and PON-1 activity decreased significantly after the treatment in both groups, but the observed decrease of these parameters in the WBC group was higher in comparison to the KT group. Conclusion: WBC procedures have a beneficial impact on inflammatory endothelium and oxidative stress parameters in healthy subjects, therefore they may be used as a wellness method.
... There is a lot of evidence that oxidative stress plays a major role in several common diseases, including cancer, obesity, diabetes, metabolic disorders, liver diseases, atherosclerosis, and cardiovascular disease [9,11,12]. Oxidative stress also plays an important role in some other diseases, such as obstructive sleep apnea syndrome, ankylosing spondylitis, Alzheimer's disease, and Parkinson's disease [13][14][15]. ...
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Objective: Pirarubicin (THP) is one of anthracycline anticancer drugs. It is widely used in the treatment of various cancers, but its hepatotoxicity cannot be ignored. Schisandrin B (SchB) is a traditional liver-protecting drug, which has the ability to promote mitochondrial function and upregulate cellular antioxidant defense mechanism. However, whether it can resist THP-induced hepatotoxicity has not been reported. The purpose of this study was to observe and explore the effect of SchB on THP-induced hepatotoxicity and its potential mechanism by adding SchB to the diet of rats with THP-induced hepatotoxicity. Methods: The rat model of THP-induced hepatotoxicity was established and partly treated with SchB diet. The changes of serum liver function indexes ALT and AST were observed. The histomorphological changes of liver were observed by HE staining. The biomarker levels of oxidative stress in rat serum and liver were measured to observe oxidative stress state. The expressions of ferroptosis-related protein GPX4 and oxidative stress-related protein were detected by Western blot. Primary hepatocytes were prepared and cocultured with THP, SchB, and Fer-1 to detect the production of reactive oxygen species (ROS) and verify the above signal pathways. Results: THP rats showed a series of THP-induced hepatotoxicity changes, such as liver function damage, oxidative stress, and ferroptosis. SchB diet effectively alleviated these adverse reactions. Further studies showed that SchB had strong antioxidant and antiferroptosis abilities in THP-induced hepatotoxicity. Conclusion: SchB has obvious protective effect on THP-induced hepatotoxicity. The mechanism may be closely related to inhibiting oxidative stress and ferroptosis in the liver.
... The term oxidative stress (OS) refers to a greater activity of pro-oxidative factors over antioxidant factors [33]. OS has been shown to be related to the pathogenesis of various diseases such as cancer, CVDs, diabetes, obesity, neurodegenerative diseases, ankylosing spondylitis, chronic obstructive pulmonary disease, and obstructive sleep apnea [34][35][36]. Significant differences in the parameters of OS were found between obese, metabolically unhealthy patients, and healthy volunteers with normal body weight [37]. Interestingly, "obesity and insulin resistance" is the component of the metabolic syndrome most strongly associated with the presence of OS (according to principal component analysis) [38]. ...
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Diabetes mellitus (DM) is a strong risk factor for the development of cardiovascular diseases (CVDs), which are the most important cause of morbidity and mortality in the population of patients living with DM. DM is associated with lipid metabolism disorders characterized by a decrease in the high-density lipoprotein blood concentration, an increase in the triglyceride blood concentration, and the presence of modified lipoproteins not routinely measured in clinical practice. Nitrated lipoproteins are produced by the nitration of the tyrosyl residues of apolipoproteins by myeloperoxidase. There is some evidence from the research conducted showing that nitrated lipoproteins may play a role in the development of cardiovascular dysfunction, but this issue requires further investigation. It was found that the nitration of HDL particles was associated with a decrease in caspase-3 and paraoxonase-1 activity, as well as a decrease in the activity of cholesterol transport via ABCA1, which reduces the protective effect of HDL particles on the cardiovascular system. Less information has been collected about the role of nitrated LDL particles. Thus far, much more information has been obtained on the relationship of nitrotyrosine expression with the presence of cardiovascular risk factors and the development of cardiovascular dysfunction. The purpose of this paper is to provide an extensive review of the literature and to present the most important information on the current state of knowledge on the association between nitrotyrosine and nitrated lipoproteins with dysfunction of the cardiovascular system, especially in patients living with DM. Moreover, directions for future research in this area were discussed.
... Since the 70 s, several forms of WBC have been applied in people suffering from autoimmune diseases such as multiple sclerosis, 22,23 ankylosing spondylitis 24,5,7 and rheumatoid arthritis. 25 Autoimmune diseases are diseases in which the immune system is overactive and causes increased inflammatory reactions, which in their turn cause tissue damage. ...
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Objective To give an overview of the nature and methodological quality of studies on whole body cryotherapy (WBC) as add-on intervention for mental health problems. Methods A meta-analysis according to PRISMA guidelines was conducted (Prospero registration: CRD42020167443). Databases MEDLINE, PsycINFO and the Cochrane Library were searched. Risk of bias was scored according to the Cochrane ROBINS-I-tool to which an extra bias-dimension of allegiance bias was added. Within and between Hedges’ g pooled effect sizes were calculated for the main aspect of mental health measured. Treatment efficacy was examined using a random effects model. Heterogeneity was examined through identification of visual outliers and by I² statistics. Results Out of 196 articles coming up from the search, ten studies met all inclusion criteria, six of which were (randomized) controlled trials. Together these studies report on a total of 294 participants receiving WBC. The within-group pooled effect size for mental health problems is large (Hedges’ g = 1.63, CI: 1.05-2.21), with high heterogeneity (I² = 93%). Subgroup analyses on depressive symptoms and quality of life (QOL) showed a diminution of heterogeneity to moderate. Effect sizes for depressive symptoms are very large (Hedges’ g = 2.95, CI: 2.44-3.45) and for QOL medium (Hedges’ g = 0.70, CI: 0.15-1.24). The between-group pooled effect size is medium (Hedges’ g = 0.76, CI: 0.17-1.36). Conclusions Results indicate preliminary evidence for WBC as efficacious add-on intervention for mental health problems, especially depressive symptoms. Further research in the form of RCTs with larger numbers of participants is needed.
... WBC-whole body cryotherapy (WBC) use the stimulating effect of extremely low temperatures (below − 100 • C) applied to the body for a period of about 3 min [2,3,6,12]. So far, WBC procedures have been commonly used in the treatment of rheumatic and inflammatory diseases such as rheumatoid arthritis [7], fibromyalgia [9,19], and ankylosing spondylitis [21,22] as well as multiple sclerosis [15], and sport medicine [18] Currently WBC is used more and more frequently as a wellness method in healthy subjects, to help maintain good health [23,24]. To sum up, this method has been used for many years to reduce pain, accelerate tissue regeneration, suppress inflammation, reduce muscle tension, improve physical fitness and as an element of biological renewal, especially in athletes [2,16]. ...
Article
Introduction The aim of the paper was to evaluate changes in selected skin parameters (hydration, sebum level and pH of the skin) after whole-body cryotherapy (WBC). Material and Methods The study encompassed of 16 individuals (8 men and 8 women), who participated in 15 WBC sessions. There were 4 measurements of skin parameters performed in the following way: prior to the first cryotherapy session, directly after the first session, after the 15th session, and after 3 weeks from the moment when the therapy was discontinued. Results No significant differences were observed for hydration and skin pH. Sebum level significantly decreased after 2nd cryotherapy session. Conclusion Whole-body cryotherapy seems to be safe for skin.
... Low temperature has an analgesic, anti-inflammatory, anti-swelling effect on the body, it also affects the circulatory, nervous, muscular and endocrine systems, as well as the rate of metabolic changes, which implies their use in disease entities related to these systems [1,3,4]. This method is used to relieve pain and inflammation in degenerative, neurological and rheumatoid diseases [5,6] as well as in the treatment of obesity [7] Among the numerous indications for cryotherapy, the use of cold treatment in patients with rheumatoid arthritis [8], fibromyalgia [9,10], ankylosing spondylitis [11,12] and multiple sclerosis [13] was the best documented. ...
Article
Introduction Systemic cryotherapy is a popular treatment involving a short stay in a cryogenic chamber at a temperature below -100 ° C. This leads to a number of physiological reactions, some of them also observed in the skin. The aim of the study was to analyze the effect of a single cryogenic treatment on selected skin characteristics (skin pH, level of hydration and TEWL – Transepidermal Water Loss) in young, healthy people. Materials and methods Skin characteristics in 77 young people (23.63 ± 1.36 years) were assessed. In the study, 43 women and 33 men who took part in a one-time treatment (-120°C) lasting 3 minutes. Measurements were made on the forearm skin and (in men) on the face twice: before and immediately after the procedure. Results: Initial differences in hydration of the stratum corneum and TEWL were observed between the group of women and men. After one treatment, the examined characteristics of the forearm skin did not change, and an unfavorable increase in TEWL in men was indicated in the facial area. Conclusions A single stay in the cryogenic chamber, while maintaining the correct methodology of the treatment, is safe for the skin. The changes taking place depend on the body surface area tested, which indicates that the skin on the limbs and on the face reacts differently to the cryogenic stimulus.
... Immunomodulation is another potential effect of WBC. Researchers have found that exposure to extremely low temperatures leads to a decrease in oxidative stress and pro-inflammatory cytokines (IL-1, IL-2, TNF-α) and an increase in the concentration of anti-inflammatory cytokines (IL-6, IL-10) (Banfi et al., 2009;Stanek et al., 2018). Markers of inflammatory response, such as C Reactive Protein (CRP) and sICAM-1 were also downregulated, which is of importance in patients with dementia due to the correlation of cognitive impairment with neuroinflammation (Bouzigon et al., 2016;Kim et al., 2012). ...
Article
Background Whole-Body Cryotherapy (WBC) - a repetitive, short-term exposure to extremely low temperatures – may become an effective early intervention for mild cognitive impairment (MCI). It is a heterogeneous group of symptoms associated with cognitive dysfunction which is estimated to transform into dementia in 50% cases. Study design The prospective randomised double-blind sham-controlled study aimed to determine the efficacy of WBC on cognitive functioning and biological mechanisms. The study was registered with Australian New Zealand Clinical Trials Registry (ACTRN12619001627145). Methods Participants with MCI (n = 62; (20 26) were randomly allocated to cryogenic temperatures (−110 °C till −160 °C) (EG, n = 33) or placebo-controlled group (CG, n = 29). Cognitive functions were measured at baseline (T1), after the 10th WBC session (T2) and after 2 week-break (T3) with DemTect, SLUMS and Test Your Memory (TYM). Secondary outcome measures included quality of life (WHOQoL–BREF), self-reported well-being (VAS) and depressive symptoms (GDS). Whole blood samples (10 ml) were collected at T1 and T2 to evaluate levels of cytokines, neurotrophins, NO and biochemical parameters CRP total cholesterol, prolactin). Results There were significant differences between groups measured at T2 in immediate recall (DemTect) and in orientation (TYM) in favour of WBC group. Improvement in mood was detected in self-reported depressive symptoms level (WHOQoL-26; T2 p = 0.04; VAS mood T2 p = 0.02; T3 p = 0.07). The significant reduction of BDNF level was observed (p < 0.05). Conclusions WBC may increase the performance of cognitive functions. It seems promising to combine WBC with existing behavioural and cognitive trainings in the future studies investigating early interventions methods in MCI.
Article
While the recent literature on Whole-Body Cryotherapy pointed to its beneficial systemic effects on inflammatory markers in rheumatoid arthritis, it was not clear whether it could also have more localized effects, with the attainment of analgesic thresholds on hands that are usually protected during protocols. Twenty-five young, healthy subjects (12 males aged 25.1 ± 3.5 years and 13 females aged 23.5 ± 2.6 years) agreed to participate in this study. Two study groups were defined: (1) a control group with a hand fully gloved and (2) an experimental group with a partially ungloved hand during the WBC session. In both groups, the achievement of analgesic thresholds of skin temperature was established through thermal imaging, focused on the measurement of temperatures at the different joint locations. Using a new protocol with direct exposure of the hands during the last 40 s of a standard WBC session of 3 min at −110 °C made it possible to respect this risk/benefit balance. Infrared thermography analyses revealed that for all regions of interest (except MCP and IP, CMP for thumb), there was a clinically meaningful reduction of skin temperature in participants from the experimental group. The thermal analysis suggests that a protocol of Whole-Body Cryotherapy at −110 °C where hands must be ungloved during 40 s could be a useful tool for the management of hand rheumatoid arthritis by achieving local antalgic thresholds.
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Objective The aim of the study was to estimate the impact of whole-body cryotherapy (WBC) on cardiovascular risk factors in patients with ankylosing spondylitis (AS). Material and Methods We investigated the effect of WBC with subsequent kinesiotherapy on markers of inflammation, oxidative stress, lipid profile, and atherosclerosis plaque in male AS patients (WBC group). To assess the disease activity, the BASDAI and BASFI were also calculated. The results from the WBC group were compared with results from the kinesiotherapy (KT) group. Results The results showed that in the WBC group, the plasma hsCRP level decreased without change to the IL-6 level. The ICAM-1 level showed a decreasing tendency. The CER concentration, as well as the BASDAI and BASFI, decreased in both groups, but the index changes of disease activity were higher in the WBC than KT patients. Additionally, in the WBC group, we observed a decrease in oxidative stress markers, changes in the activity of some antioxidant enzymes and nonenzymatic antioxidant parameters. In both groups, the total cholesterol and LDL cholesterol, triglycerides, sCD40L, PAPP-A, and PLGF levels decreased, but the parameter changes were higher in the WBC group. Conclusion WBC appears to be a useful method of atherosclerosis prevention in AS patients.
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Objective The primary aim of the study was to assess levels of oxidative stress markers, soluble CD40 ligand (sCD40L), serum pregnancy-associated plasma protein-A (PAPP-A), and placental growth factor (PlGF) as well as carotid intima-media thickness (IMT) in patients with ankylosing spondylitis (AS) with active phase without concomitant classical cardiovascular risk factors. Material and methods The observational study involved 96 male subjects: 48 AS patients and 48 healthy ones, who did not differ significantly regarding age, BMI, comorbid disorders, and distribution of classical cardiovascular risk factors. In both groups, we estimated levels of oxidative stress markers, lipid profile, and inflammation parameters as well as sCD40L, serum PAPP-A, and PlGF. In addition, we estimated carotid IMT in each subject. Results The study showed that markers of oxidative stress, lipid profile, and inflammation, as well as sCD40L, PlGF, and IMT, were significantly higher in the AS group compared to the healthy group. Conclusion Our results demonstrate that ankylosing spondylitis may be associated with increased risk for atherosclerosis.
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Patients with rheumatoid arthritis (RA) have increased oxidative stress, decreased antioxidant levels, and impaired antioxidant capacity. Cold treatments are used to relieve joint inflammation and pain. Therefore, we measured the effect of cold treatments on the antioxidative capacity of RA patients with active disease. Sixty patients were randomized to (1) whole body cryotherapy at -110 °C, (2) whole body cryotherapy at -60 °C, or (3) local cryotherapy. Each treatment was given three times daily for 7 consecutive days in addition to the conventional rehabilitation. Blinded rheumatologist evaluated disease activity before the first and after the last cryotherapy. We collected plasma samples daily immediately before the first and after the second cryotherapy and measured total peroxyl radical trapping antioxidant capacity of plasma (TRAP), which reflects global combined antioxidant capacity of all individual antioxidants in plasma. Baseline morning TRAP levels (mean, 95% CI), adjusted for age, body mass index, disease activity, and dose of prednisolone, were 1244 (1098-1391) µM/l in the local cryotherapy, 1133 (1022-1245) µM/l in the cryotherapy at -60 °C, and 989 (895-1082) µM/l in the cryotherapy at -110 °C groups (p = 0.006). After the first treatment, there was a rise in 1-h TRAP of 14.2 (-4.2 to 32.6) µM/l, 16.1 (-7.4 to 39.6) µM/l, and 23.6 (4.1-43.2) µM/l, respectively. The increase was significant in the whole-body cryotherapy -110 °C group (p < 0.001) but not significant between the groups (p = 0.78). When analyzed for the whole week, the daily morning TRAP values differed significantly between the treatment groups (p = 0.021), but there was no significant change within each treatment group. Whole-body cryotherapy at -110 °C induced a short-term increase in TRAP during the first treatment session with but not during other treatment modalities. The effect was short and the cold treatments did not cause a significant oxidative stress or adaptation during 1 week.
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Background The purpose of this study was to verify the effect of whole-body cryotherapy (WBC) in rats on their antioxidant systems, lipid peroxidation products, and their total oxidative status at different exposure times and temperatures. Methods Antioxidants in serum, plasma, liver, and erythrocytes were evaluated in two study groups following 1 min of exposure to −60°C and −90°C, for 5 and 10 consecutive days. Results WBC increased the activity of superoxide dismutase, catalase in the group subjected to 5 and 10 days exposure, −60°C. The glutathione S-transferase activity increased in the groups subjected to 10 days WBC sessions. Total antioxidant capacity increased after 5 and 10 days of 1 min WBC, −60°C; a decrease was observed at −90°C. A decreased level of erythrocyte malondialdehyde concentration was observed at −60°C after 5 and 10 days of cryostimulation. An increased concentration was measured at −90°C after 10 days, and increase of erythrocyte malondialdehyde concentration after 5 days, −90°C. Conclusions To the best of our knowledge, this is the first research showing the effect of WBC in rats at different exposure times and temperatures. The effect of cryotherapy on enzymatic and nonenzymatic antioxidant systems was observed in the serum of animals exposed to a temperature of −60°C in comparison to control.
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Nowadays, whole-body cryotherapy is a medical physical treatment widely used in sports medicine. Recovery from injuries (e.g., trauma, overuse) and after-season recovery are the main purposes for application. However, the most recent studies confirmed the anti-inflammatory, anti-analgesic, and anti-oxidant effects of this therapy by highlighting the underlying physiological responses. In addition to its therapeutic effects, whole-body cryotherapy has been demonstrated to be a preventive strategy against the deleterious effects of exercise-induced inflammation and soreness. Novel findings have stressed the importance of fat mass on cooling effectiveness and of the starting fitness level on the final result. Exposure to the cryotherapy somehow mimics exercise, since it affects myokines expression in an exercise-like fashion, thus opening another possible window on the therapeutic strategies for metabolic diseases such as obesity and type 2 diabetes. From a biochemical point of view, whole-body cryotherapy not always induces appreciable modifications, but the final clinical output (in terms of pain, soreness, stress, and post-exercise recovery) is very often improved compared to either the starting condition or the untreated matched group. Also, the number and the frequency of sessions that should be applied in order to obtain the best therapeutic results have been deeply investigated in the last years. In this article, we reviewed the most recent literature, from 2010 until present, in order to give the most updated insight into this therapeutic strategy, whose rapidly increasing use is not always based on scientific assumptions and safety standards.
Article
To update and integrate the recommendations for ankylosing spondylitis and the recommendations for the use of tumour necrosis factor inhibitors (TNFi) in axial spondyloarthritis (axSpA) into one set applicable to the full spectrum of patients with axSpA. Following the latest version of the European League Against Rheumatism (EULAR) Standardised Operating Procedures, two systematic literature reviews first collected the evidence regarding all treatment options (pharmacological and non-pharmacological) that were published since 2009. After a discussion of the results in the steering group and presentation to the task force, overarching principles and recommendations were formulated, and consensus was obtained by informal voting. A total of 5 overarching principles and 13 recommendations were agreed on. The first three recommendations deal with personalised medicine including treatment target and monitoring. Recommendation 4 covers non-pharmacological management. Recommendation 5 describes the central role of non-steroidal anti-inflammatory drugs (NSAIDs) as first-choice drug treatment. Recommendations 6–8 define the rather modest role of analgesics, and disprove glucocorticoids and conventional synthetic disease-modifying antirheumatic drugs (DMARDs) for axSpA patents with predominant axial involvement. Recommendation 9 refers to biological DMARDs (bDMARDs) including TNFi and IL-17 inhibitors (IL-17i) for patients with high disease activity despite the use (or intolerance/contraindication) of at least two NSAIDs. In addition, they should either have an elevated C reactive protein and/or definite inflammation on MRI and/or radiographic evidence of sacroiliitis. Current practice is to start with a TNFi. Switching to another TNFi or an IL-17i is recommended in case TNFi fails (recommendation 10). Tapering, but not stopping a bDMARD, can be considered in patients in sustained remission (recommendation 11). The final two recommendations (12, 13) deal with surgery and spinal fractures. The 2016 Assessment of SpondyloArthritis international Society-EULAR recommendations provide up-to-date guidance on the management of patients with axSpA.