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Effect of PCSO-524 on OA Biomarkers and Weight-Bearing Properties in Canine Shoulder and Coxofemeral Osteoarthritis

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This study was designed to compare the therapeutic benefits of a compound of omega-3 fatty acids from the New Zealand green-lipped mussel (Perna canaliculus) (PCSO-524) and omega-3 fatty acids in fish oil on clinical outcomes and osteoarthritis biomarkers (chondroitin sulfate WF6 epitope) in 66 dogs that had osteoarthritis (OA); 39 dogs with OA hip joints, 15 dogs with OA shoulder joints and 12 dogs with OA shoulder and hip joints. The animals were presented at the Small Animal Hospital, Faculty of Veterinary Science, Chulalongkorn University. The dogs were allocated into two groups randomly. One group received PCSO-524 (n = 33) and the other group received fish oil (n = 33), administered orally for 24 weeks. Serum OA biomarkers (WF6), lameness scores, weight-bearing scores, range of motion (ROM) and peak vertical force gait analysis were evaluated before treatment and two, four, eight, 12, 16, 20 and 24 weeks after the treatment began. The mean of serum WF6 of the PCSO-524 group (262.46±118.06 ng/ml) was significantly (p < 0.05) less than that of the fish oil group (324.76±133.65 ng/ml) after 24 weeks of administration. The lameness scores, weight-bearing scores, peak vertical force gait analysis results and ROM improved significantly within two weeks after the administration of PCSO-524 began, while there was no statistically significant improvement in any of the parameters of the fish oil group after 12 weeks. After week four, the lameness and weight-bearing scores and gait analysis results of the PCSO-524 group improved significantly by comparison with the fish oil group. In conclusion, the PCSO-524 administration led to good clinical outcomes and laboratory results of osteoarthritis of the shoulder and hip joints in dogs.
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Thai J Vet Med. 2015. 45(2): 157-165.
Effect of PCSO-524 on OA Biomarkers and Weight-Bearing
Properties in Canine Shoulder and Coxofemeral Osteoarthritis
Kumpanart Soontornvipart1* Natwadee Mongkhon1 Korakot Nganvongpanit2
Prachya Kongtawelert3
Abstract
This study was designed to compare the therapeutic benefits of a compound of omega-3 fatty acids from the
New Zealand green-lipped mussel (Perna canaliculus) (PCSO-524) and omega-3 fatty acids in fish oil on clinical
outcomes and osteoarthritis biomarkers (chondroitin sulfate WF6 epitope) in 66 dogs that had osteoarthritis (OA); 39
dogs with OA hip joints, 15 dogs with OA shoulder joints and 12 dogs with OA shoulder and hip joints. The animals
were presented at the Small Animal Hospital, Faculty of Veterinary Science, Chulalongkorn University. The dogs were
allocated into two groups randomly. One group received PCSO-524 (n = 33) and the other group received fish oil (n =
33), administered orally for 24 weeks. Serum OA biomarkers (WF6), lameness scores, weight-bearing scores, range of
motion (ROM) and peak vertical force gait analysis were evaluated before treatment and two, four, eight, 12, 16, 20 and
24 weeks after the treatment began. The mean of serum WF6 of the PCSO-524 group (262.46±118.06 ng/ml) was
significantly (p<0.05) less than that of the fish oil group (324.76±133.65 ng/ml) after 24 weeks of administration. The
lameness scores, weight-bearing scores, peak vertical force gait analysis results and ROM improved significantly within
two weeks after the administration of PCSO-524 began, while there was no statistically significant improvement in any
of the parameters of the fish oil group after 12 weeks. After week four, the lameness and weight-bearing scores and gait
analysis results of the PCSO-524 group improved significantly by comparison with the fish oil group. In conclusion,
the PCSO-524 administration led to good clinical outcomes and laboratory results of osteoarthritis of the shoulder and
hip joints in dogs.
Keywords: canine, fish oil, green-lipped mussel, osteoarthritis, PCSO-524, WF6
1Department of Veterinary Surgery, Faculty of Veterinary Science, Chulalongkorn University, Bangkok 10330, Thailand
2Department of Veterinary Preclinical Science, Faculty of Veterinary Medicine, Chiang Mai University, Chiang Mai 50100,
Thailand
3Thailand Excellence Center for Tissue Engineering, Department of Biochemistry, Faculty of Medicine, Chiang Mai University,
Chiang Mai 50200, Thailand
*Correspondence: skumpana@gmail.com
Original Article
158 Soontornvipart K. et al. / Thai J Vet Med. 2015. 45(2): 157-165.
Introduction
The understanding of the pathogenesis of
osteoarthritis (OA) is still unclear. Many researchers
believed that the causes of OA could be articular
cartilage changes such as structure, biochemistry and
metabolism, which might be influenced by one or a
combination of genetic factors, overuse, accidents,
aging, dietary and inflammatory factors (Burnett et al.,
2006; Bennett, 2010). The prevalence of canine
osteoarthritis increased from 15% to 67% as dogs aged
(Gail et al., 2006). Moreover, another study showed
that canine OA affected about 20% of dogs that were
more than one year old (Johnston, 1997).
According to the pathogenesis and clinical
outcomes of OA, there are two purposes of OA
management, which are to relieve pain and to prevent
OA progression. Surgical, medical andor
nutraceuticals are provided to achieve these aims
(Wang et al., 2004). The development of nutraceuticals
has led to the hope that inhibition of the inflammatory
pathway can cause a reduction in articular
degradation. For this reason, the anti-inflammatory
properties of omega-3 polyunsaturated fatty acids
(omega-3 PUFAs) have attracted great interest as a
possible OA treatment. There are many types of
omega-3 PUFAs, of which eicosapentaenoic acid
(EPA), docasahexaenoic acid (DHA) and
eicosatetraenoic acid (ETA) are the three best-known
types (Yuan et al., 2006; Treschow et al., 2007; Roush et
al., 2010). Many clinical researchers revealed that both
green-lipped mussel extract (GLM) and fish oil (EPA
18% and DHA 12%) could reduce pain and increase
joint mobility in OA cases because they had an anti-
inflammatory effect. Many researchers demonstrated
that omega-3 PUFAs (especially ETA and EPA) might
affect the LOX and COX pathways by reducing the
production of leukotrienes and prostaglandins
(Whitehouse et al., 1997; Dugas, 2000; Murphy et al.,
2002). Identification of GLM components found a
predominant PUFA (ETA) structure that was similar to
arachidonic acid. As a result of a reduction in LOX
production, the PUFAs in GLM might be a significant
anti-inflammatory compound (Treschow et al., 2007).
Recently, Roush et al. (2010), Hielm-Bjorkman
et al. (2012) and Zawadzki et al. (2013) have evaluated
the effects of fish oil on weight bearing in OA dogs.
Moreover, other researchers showed that greater EPA
and DHA concentrations could improve the clinical
signs (lameness and weight bearing) of OA dogs
(Fritsch et al., 2010a; Fritsch et al., 2010b). Another
study on the use of GLM in OA dogs found that the
clinical signs improved significantly after six weeks
(Bierer and Bui, 2002).
PCSO-524 has a huge difference in efficacy
between other mussel extracts and powders due to the
patented CO2 extracted oil (Whitehouse et al., 1997).
Recently, there has been growing interest in
osteoarthritis biomarkers as primary outcome
measures. Although considerable research has been
devoted to clinical signs of improvement, rather less
attention has been paid to OA biomarkers as a mean by
which to monitor disease activity and predict disease
progression. Thus, the aim of this study was to
examine the positive effect of PCSO-524 (a long-chain
omega-3 PUFA compound from the New Zealand
green-lipped mussel) on the osteoarthritis biomarker
level, weight-bearing properties in the treatment of
canine shoulder and coxofemoral osteoarthritis
compared to fish oil.
Materials and Methods
Sixty-six dogs showed signs of coxofemoral
and/or shoulder osteoarthritis, which included limb
lameness, joint pain, stiffness and decreased range of
motion (ROM) (Millis, Taylor, & Levine, 2004).
Moreover, the evidence of OA at coxofemoral or
shoulder joints was indicated in radiographs (Sirois et
al., 2010). The dogs were only fed commercial standard
food (Royal Canin® mature large breed) for at least two
weeks before the study. The exclusion criteria during
this study were: 1. severe liver, gastrointestinal,
urogenital, or neurological problems and/or pregnant;
2. previous OA treatment with other drugs or dietary
supplements; and 3. a pain-score evaluation of more
than five points on the scale of the Glasgow Composite
Measure Pain Score-Short Form (Gaynor and Muir,
2009). Animal owner informed consents were gained
and the trial procedures were approved by the Faculty
of Veterinary Science, Chulalongkorn University’s
Ethics Committee, Bangkok, Thailand (No. 12310001).
The 66 OA dogs were divided into two
groups by blind randomized sampling (Table 1). The
PCSO-524 group (produced by MacLab in Nelson,
New Zealand (Gibson, 2000) (n = 33) were fed PCSO-
524 with the recommended dosage (50mg/10kg body
weight) once daily. The fish oil group (n = 33) received
fish oil with the recommended dosage (1,000 mg/dog
twice daily) produced by Mega Lifesciences (Thailand)
(Table 2). The animals were reassessed at weeks two
(W2), four (W4), eight (W8), 12 (W12), 16 (W16), 20
(W20) and 24 (W24) for clinical evaluations and blood
collection. The owners' preferences were assessed
monthly. The treatment was terminated at the end of
the sixth month.
The severity of clinical lameness and OA
scoring were evaluated and recorded before (D0) and
after treatment, as well as at weeks two, four, eight, 12,
16, 20 and 24 by the use of the clinical scoring system
(Table 3) and the measurement of range of motion
(ROM - using a goniometer) by the same veterinarian
(Millis et al., 2004; McCarthy et al., 2007). The OA
scoring was defined by using radiographic and clinical
lameness correlation. Double measurement of ROM
was required in each position of assessment and mean
was calculated and recorded. The veterinarian was
blinded to group classification when he scored. Peak
vertical force gait analysis was performed in each leg
while the dogs were standing and walking for 3 times
by using the platform system (Chalayon et al., 2013).
Data were averaged, analyzed and scoring
collaborated with weight-bearing properties compared
with the expected normal weight-bearing properties in
each leg (Table 3). The normal ratio between forelimbs
and hind limbs is 60:40. The average weight-bearing
peak vertical force was calculated by comparison with
the expected weight bearing of each limb. The
lameness scores were defined as improved, not
improved and worsened if there were different
Soontornvipart K. et al. / Thai J Vet Med. 2015. 45(2): 157-165. 159
lameness scores before and after treatment. The peak
vertical forces of the improved group should be better
than 5% of normal expected values.
Four milliliter blood samples were collected
from each dog at pre-treatment and at weeks two, four,
eight, 12, 16, 20 and 24 post-treatments. One milliliter
was separated into two parts for complete blood counts
(CBCs) and blood chemistry tests (alanine
aminotransferase, aspartate aminotransferase, blood
urea nitrogen and creatinine). The CBCs samples were
kept in anticoagulant (100IU/ml heparin; APS Finchem,
Australia). The analysis was performed only three
times, before weeks 12, 24 and after treatment, to
evaluate the health of animals. To prepare OA
biomarker samples, three milliliters of blood was
centrifuged at 7,000 x g for 15 minutes to obtain about
one milliliter of serum. This serum was frozen at -20oC
until a biomarker assay was performed. The
competitive inhibition quantitative enzyme-linked
immunosorbent assay (ELISA) method was applied.
The ELISA detected the monoclonal antibody WF6,
which was the primary antibody (Tangkijvanich et al.,
2003). Then, the samples were added to microplate
wells that were prepared with embryonic shark
skeletal cartilage aggrecan to be a coating antigen, or to
be a competitor. Next, peroxidase conjugated anti-
mouse immunoglobulin M (IgM) antibody was added
as a secondary antibody and the sample was
incubated. To encourage concentration of the epitope
WF6, the substrate was added and absorbance was
determined. Finally, the concentration of the epitope
WF6 was calculated and recorded.
Table 1 Signalment of animals
Group
Number
(N)
Joint
(n)
Age (year)
(mean [SD])
Sex
(N)
PCSO-524
33
Hip (42)
Shoulder (7)
7.65 (1.84)
Female (14)
Male (19)
Fish oil
33
Hip (40)
Shoulder (4)
6.65 (1.79)
Female (18)
Male (15)
Table 2 Composition of PCSO-524* and fish oil**
Group of treatment
Composition of a capsule
Dose
PCSO-524
(50 mg/capsule)
- Perna canaliculusoil 50 mg
- Vitamin E 0.225 mg
- Others: olive oil, gelatin and glycerine
1 capsule per 10 kg
once daily
(8 weeks)
Fish oil
(1000 mg/capsule)
Fish oil 1,000 mg
- EPA 180 mg
- DHA 120 mg
- Vitamin E 1.4 mg
1 capsule per dog
once daily
(8 weeks)
*MacLab in Nelson, New Zealand ** Mega Lifesciences (Thailand)
Table 3 Weight bearing properties measured by peak vertical force gait analysis. Data were analyzed as percentage of expected
weight bearing in each leg: 60:40, forelimbs: hind limbs.
Joint
Patients with OA in hip joints
(percentage of mean [SD])
Patients with OA in shoulder joints
(percentage of mean [SD])
Time
D0
W2
W8
W16
W24
D0
W2
W8
W16
W24
PCSO-524
Fish oil
64.5
(6.43)
79.3
(4.32)
82.1
(8.42)
88.7
(5.11)
89.2
(5.81)
68.1
(4.18)
81.4
(7.12)
86.7
(3.84)
89.3
(6.18)
91.2
(2.12)
66.8
(8.41)
68.4
(5.31)
70.1
(9.21)
71.5
(8.76)
72.3
(3.14)
67.8
(9.42)
68.9
(7.63)
70.4
(8.43)
71.2
(9.44)
71.6
(4.56)
For observation of the supplements’ side
effects, we used a routine coagulation test as screening.
Buccal mucosal bleeding time was measured before the
treatment commenced and at weeks 12 and 24 after
PCSO-524 and fish oil administration. If the dogs had
prolonged bleeding time (more than 2.6 minutes),
coagulogram (activated partial thromboplastin time,
prothrombin time and thrombin time) was performed
(Jergans et al., 1987).
The concentration of OA biomarkers (WF6)
from the serum and ROM were reported as mean ± SD
each week in the same treatment. The paired t-test
procedure was used to test for differences between
before and after treatment in the same group.
Comparison between groups was analyzed using an
unpaired t-test. The clinical sign scores was calculated
as mean ± SD using the non-parametric two samples
Mann Whitney procedure (Powers and Knapp, 2010).
Relative data were analyzed using the SPSS program
(SPSS). p-values less than 0.05 were considered to be
significant.
Results
CBCs and serum chemistry were evaluated in
all dogs at D0 and W24. Most of the values were not
significantly different between D0 and W24 (p>0.05)
(Table 4). All means of parameters were in normal
range at both D0 and W24 in the two groups. There was
no significant difference in CBCs and blood chemistry
160 Soontornvipart K. et al. / Thai J Vet Med. 2015. 45(2): 157-165.
between the PCSO-524 group and the fish oil group at
both D0 and W24 (Table 4). The buccal mucosal
bleeding times were normal and there were no
significant differences before and after treatment in
either group.
The serum of 66 dogs was evaluated by the
CS-WF6 epitope concentration (Fig 1). The levels of
serum CS-WF6 epitope at D0 were not significantly
different between the groups. In the PCSO-524 group
(n = 33) the level of serum CS-WF6 epitope was
significantly lower at W2, W4, W8, W12, W16, W20 and
W24 compared with the level at D0. In the fish oil
group (n = 33) the level of serum CS-WF6 epitope at
W8 and W20 was significantly greater than that before
the treatment commenced (D0). There was a significant
difference in CS-WF6 concentration between the
groups at the 24th week after the treatment
commenced.
The evaluations of the weight-bearing score
in 82 hip joints were performed eight times within 24
weeks (Fig 2). Results revealed that the mean scores for
weight bearing in the PCSO-524 group showed
significant improvement (p<0.05) at W2 to W24,
respectively, while in the fish oil group they were not
significantly different during the first 12 weeks of
treatment. The means of weight-bearing scores were
significantly different between the groups after four
weeks of administration (p<0.05). Eleven shoulder
joints were evaluated for weight-bearing scores (Fig 3).
Results revealed that the mean scores for weight
bearing in the PCSO-524 group showed significant
improvement (p<0.05) after the first two weeks of
administration compared with D0, while in the fish oil
group they were not significantly different within the
treatment period. The means of weight-bearing scores
were significantly different between the groups at W4,
W8, W12, W16, W20 and W24 (p<0.05). The OA dogs
were evaluated for clinical outcomes (lameness and
weight bearing) by joints that were affected separately.
Eighty-two hip joints and 11 shoulder joints that were
assessed by clinical scoring was categorized into three
groups: improved, not improved and worsened after
24 weeks of the administration of PCSO-524 (Table 5).
Table 4 Comparison of CBCs and blood chemistry profiles between pre-treatment (D0) and post-treatment (W24) within group.
Parameters
Normal range
(Bennett, 2010)
D0
W24
p-value
PCSO-524
Fish oil
PCSO-524
Fish oil
PCSO-524
Fish oil
R.B.C.x103 (cell/µl)
Hemoglobin (g/dl)
Hematocrit (%)
Platelet x103 (cell/µl)
W.B.C. x103 (cell/µl)
Neutrophils (%)
Eosinophils (%)
Basophils (%)
Lymphocytes (%)
Monocytes (%)
ALT (U/I)
ALP
BUN (mg%)
Creatinine (mg%)
5.2-8.06
12.4-19.1
29.8-57.5
160-525
5.4-15.3
51-84
0-9
0-1
8-38
1-9
4-91
3-60
7-26
0.6-1.4
6.15±1.32
14.41±2.47
41.66±6.21
289.47±81.29
10.00±3.76
71.60±9.92
2.26±2.92
0.21±0.51
17.34±7.46
6±2.29
34.43±10.16
57.21±31.44
16.17±7.85
1.1±0.38
6.62±0.78
15.35±1.68
44.22±4.80
297.47±61.64
11.10±2.86
72.95±6.88
2.91±2.69
0.04±0.20
16.13±5.96
6.00±1.88
58.89±27.79
62.86±31.39
14.65±3.92
0.94±0.22
6.38±1.19
14.76±2.26
42.25±6.30
293.52±67.65
10.04±2.49
70.91±7.75
2.08±2.37
0.21±0.67
15.82±5.41
5.21±2.77
35.69±9.63
56.52±20.5
15.29±5.65
1.07±0.47
6.93±0.73
15.58±1.3
45.31±5.26
286.34±46.34
10.27±1.69
71.08±8.17
2.04±1.74
0.17±0.38
14.60±6.23
5.52±2.15
34.13±12.67
56.56±20.83
16.69±4.64
0.90±0.20
0.2712
0.3087
0.3769
0.4276
0.4842
0.3961
0.4129
0.5000
0.2165
0.1517
0.3345
0.4466
0.3120
0.4196
0.0901
0.3029
0.2333
0.2462
0.1206
0.2030
0.1003
0.0811
0.2011
0.2133
0.1256
0.1280
0.4026
0.2983
p-values between pre-treatment (D0) and the end of treatment (W24) in the PCSO-524 and fish oil groups. R.B.C: red blood cell,
W.B.C: white blood cell, ALT: alanine aminotransferase, ALP: alkaline phosphatase, BUN: blood urea nitrogen. Data are expressed
as mean±SD.
Table 5 Clinical outcomes after 24 weeks of PCSO-524 administration (hip and shoulder joints; n = 49)
Clinical outcomes (%)
Improved
Not improved
Worsened
Lameness score
43 (87.76%)
4 (8.16%)
2 (4.08%)
Weight-bearing score
39 (79.59%)
8 (16.33%)
2 (4.08%)
Soontornvipart K. et al. / Thai J Vet Med. 2015. 45(2): 157-165. 161
Figure 1 Mean of the levels of serum chondroitin sulfate epitope (CS-WF6; ng/ml). *Values were significantly different compared
with D0 within the groups (p<0.05). aValues were significantly different between the groups within the week (p<0.05).
Figure 2 Mean of weight-bearing scores (hip joints). *Values were significantly different compared with D0 within the groups
(p<0.05). aValues were significantly different between the groups within the week (p<0.05).
Figure 3 Mean of weight-bearing scores (shoulder joints). *Values were significantly different compared with D0 within the groups
(p<0.05). aValues were significantly different between the groups within the week (p<0.05).
**a *a *a *a *a *a
a*a *a *a *a
a
0
100
200
300
400
500
D0 W2 W4 W8 W12 W16 W20 W24
Mean of WF6 concentration
(ng/ml)
Mean of WF6 epitope concentration
PCSO-524
Fish oil
*a *a *a *a *a *a
aaa*a *a *a
Mean of weight-bearing scores
Mean of weight-bearing scores (hip joints)
PCSO-524
Fish oil
*
*
* a * a * a* a * a * a
aaa
Mean of weight-bearing scores
Mean of weight-bearing scores (shoulder joints)
PCSO-524
Fish oil
a
a a
162 Soontornvipart K. et al. / Thai J Vet Med. 2015. 45(2): 157-165.
The peak vertical force was calculated into
percentage compared to the normal weight- bearing
properties (forelimb = 30% and hind limb = 20%). The
peak vertical force (PVF) while standing and walking
in the PCSO-524 group significantly improved than in
the fish oil group since the 2nd week of administration
in the forelimbs and hind limbs (Table 5 and 6). ROMs
were acquired from 46 dogs, which were divided into
two groups (Table 7). In the PCSO-524 group there
were 42 hip joints and seven shoulder joints. In the fish
oil group there were 40 hip joints and four shoulder
joints.
Table 6 Clinical outcomes after 24 weeks of fish oil administration (hip and shoulder joints; n = 44)
Clinical outcomes (%)
Improved
Not improved
Worsened
Lameness score
14 (31.81%)
24 (54.55%)
6 (13.64%)
Weight-bearing score
13 (29.55%)
22 (50.00%)
9 (20.45%)
Table 7 Mean (SD) of ROMs in the PCSO-524 group and the fish-oil group
Joint
Hip joints (mean [SD])
Shoulder joints (mean [SD])
Time
D0
W2
W8
W16
W24
D0
W2
W8
W16
W24
Flex
(degree)
PCSO-
524
40.11
(7.50)
34.57*
Ϯ
(6.87)
33.32*
Ϯ
(4.79)
33.44*Ϯ
(4.76)
32.03*Ϯ
(4.64)
51.93
(9.32)
41.93*Ϯ
(8.99)
38.43*Ϯ
(6.98)
38.73*Ϯ
(7.86)
36.75*Ϯ
(5.80)
Fish oil
39.25
(6.63)
38.51
Ϯ
(7.01)
39.55
Ϯ
(6.03)
34.15 *
Ϯ
(5.65)
32.45*
Ϯ
(5.55)
53.16
(3.01)
51.33
Ϯ
(1.89)
51.50
Ϯ
(2.78)
49.41 * Ϯ
(0.87)
46.33*
Ϯ
(1.37)
Extend
(degree)
PCSO-
524
122.60Ϯ
(10.74)
130.6*
(11.74)
135.91*
(10.02)
137.48*
(8.48)
137.90*
(7.96)
121.75Ϯ
(4.66)
127.87*Ϯ
(5.8)
132.31*
(10.74)
134.31*
(8.17)
136.58*
(5.80)
Fish oil
130.60Ϯ
(11.41)
132.21
(7.98)
134.89
(6.33)
136.53*
(5.65)
138.74*
(5.35)
136.66Ϯ
(5.77)
136.33Ϯ
(5.34)
137.16
(4.90)
139.5*
(6.94)
139.00*
(4.82)
*Values were significantly different compared with the pre-treatment (D0) values within the groups (p<0.05).
ϮValues were significantly different between the groups within the week (p<0.05).
Discussion
The results of this study revealed that the
lameness score, peak vertical force weight-bearing
score and ROM in the PCSO-524 group showed
significantly greater improvement than those in the
fish oil group. The level of the WF6 epitope was
significantly less than that of the fish oil group. These
results supported the improvement of OA signs and
the slow OA progression among the dogs that were
given PCSO-524. This was in accord with previous
studies which found that OA dogs had greater
lameness scores and a greater concentration of WF6
epitope than those found in normal dogs
(Nganvongpanit et al., 2008a; Trakulsantirat et al.,
2011). The subjective assessment of OA signs is inferior
to an objective assessment obtained from force-
platform gait analysis (Roush et al., 2010). The clinical
outcomes in the present study, however, were assessed
by the same blinded veterinary orthopedist who has
extensive experience in the treatment of OA. This study
found that the clinical lameness and the peak vertical
force weight-bearing properties correlated and
improved in the PCSO-524 group, whereas those in the
fish oil group worsened at four weeks after the
administration commenced. The percentage of clinical
outcomes after 24 weeks of PCSO-524 administration
revealed a progression of lameness and weight-bearing
scores of only 4.08%. One dog required surgical
intervention at the femoral head and neck excision.
Rehabilitation, NSAIDs and omega-3 were applied for
pain relief and to assist in the return of limb function.
The veterinarian decided to give more treatment
because the pain score evaluation was more than five
points on the scale of the Glasgow Composite Measure
Pain Score-Short Form (Gaynor and Muir, 2009).
Previous studies investigated the serum WF6
epitope level and the alteration of the articular
cartilage, which was more sensitive to joint cartilage
degradation (Nganvongpanit et al., 2008a; Pruksakorn
et al., 2009). Therefore, the released serum WF6 from
extracellular matrix of joint cartilage is due to the
destruction of cartilage and the assay should be proven
for monitoring OA treatment or before and after
traumatic arthritis detection (Pruksakorn et al., 2009).
The results showed that the serum WF6 epitope
concentration in the PCSO-524 group was significantly
less than the concentration in the fish oil group at the
end of study. It is interesting that PCSO-524 may
decrease the cartilage destruction in OA dogs and the
effect was detected after two weeks of administration.
At W12 the PCSO-524 group showed that a mildly
increased WF6 level could result from an induced
catabolic process of the articular cartilage, but joint
metabolism recovered to maintain the balance of the
joint metabolism (Nganvongpanit et al., 2008b). On the
other hand, the dogs to which fish oil were
administered continued to experience joint cartilage
degradation, as indicated by an increase in the WF6
epitope concentration. The trend of the WF6 level of the
fish oil group was decreased slightly after W12. A
further long-term study should be performed. A
systematic review of research on the efficacy of
nutraceuticals for the relief of the clinical signs of
osteoarthritis examined 22 papers. Although the
conclusion was that the efficacy of nutraceuticals was
poor, omega-3 fatty acid in dogs was the exception
(Van de Weerd et al., 2012). The efficacy of omega-3 use
Soontornvipart K. et al. / Thai J Vet Med. 2015. 45(2): 157-165. 163
in OA dogs varies according to the source, the omega-
3 to omega-6 ratio, the volume of EPA and DHA and
also the extraction method and subsequent processing.
The carrier elements and the anti-oxidant used to
stabilize an active ingredient also have an effect on the
efficacy (Whitehouse et al., 1997; Treschow et al., 2007;
Fritsch et al., 2010a; Fritsch et al., 2010b). A study
revealed that high EPA and DHA concentrations in
food (approximately 2.94% of dry weight) and a high
omega-3 to omega-6 fatty acid ratio (approximately
2.19) improved the clinical outcome significantly after
90 days (Fritsch et al., 2010a). Another study found that
the lameness and weight-bearing scores of 38 OA dogs
improved after they received a diet that contained 3.5%
omega-3 fatty acids (fish oil) (Roush et al., 2010). These
results were the opposite of what this study found,
however the period of the study of Roush (2010) was
only 60 days. The result of a consistent dose of fish oil
in dogs is not understood well because there have been
only a small number of animal studies. The adverse
effect is that EPA may inhibit blood clotting. There are
no known adverse effects of DHA (Beale, 2004). The
impact on blood clotting was measured twice
(monthly) during the term of a study, by recording the
buccal mucosal bleeding. All the dogs experienced
normal bleeding (less than 2.6 minutes) (Jergans et al.,
1987). It should also be borne in mind that the omega-
3 and omega-6 content of each product is different
because of source variation and different processes.
The source of an omega-3 has been shown to have a
great bearing on its efficacy. Omega-3 chains extracted
from the New Zealand green-lipped mussel (Perna
canaliculus) have been shown to be much more potent
than fish oil as an anti-inflammatory (Whitehouse et
al., 1997). Omega-3 fatty acids in fish oil include EPA
and DHA (Fritsch et al., 2010a), but those in PCSO-524
include compound fatty acids (ETA, EPA, DHA, etc.)
(Treschow et al., 2007). Although PCSO-524 is a GLM
extract, it is different from other GLM products. PCSO-
524 is the result of a patented extraction and
stabilization process part of which a super-critical fluid
process is used (Whitehouse et al., 1997; Treschow et
al., 2007; Soontornvipart and Mongkhon, 2012). PCSO-
524 is a lipid-rich extract that improved OA signs and
delayed cartilage degradation at the second week after
administration in the present study. A new study of 12
weeks of PCSO-524 administration to dogs that had
OA at shoulder, hip and/or stifle joints and cauda
equine syndrome revealed that a large percentage of
dogs improved in clinical lameness (Mongkon and
Soontornvipart, 2012). These studies provide evidence
of the efficacy of GLM. The present study found that
the unique composition of PCSO-524 provided a faster
rate of improvement than the GLM powder. A study
that compares the efficacy of different GLM extracts
will provide useful data. Another advantage of PCSO-
524 is that it can be used in the long term without
adverse side effects (Beale, 2004; Wang et al., 2004) to
treat OA, provide pain relief and help dog to regain
limb function quickly (Bennett, 2010; Nelson et al.,
2006). This study indicated that PCSO-524 had a
greater therapeutic effect on OA dogs than fish oil. The
administration of PCSO-524 can improve clinical signs
and ROM, and decrease the level of serum WF6 epitope
in canine shoulder and coxofemoral osteoarthritis.
There were no proven side effects in either of the
nutraceuticals administered during this clinical trial.
The analyses of complete blood counts and blood
chemistry were not different between pre-treatment
and the end of this study.
In conclusion, the PCSO-524 administration
led to good clinical outcomes and laboratory results of
osteoarthritis of the shoulder and hip joints in dogs.
The fish oil did not show any positive effects in the
canine osteoarthritic treatment.
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


กัมปนาท สุนทรวิภาต1* ณัฐวดี มงคล1 กรกฏ งามวงศ์พาณิชย์2 ปรัชญา คงทวีเลิศ3
 
 (PCSO-524)      

 PCSO-524 (n = 33) 
(n = 33) (WF6)

        WF6  PCSO-524
(262.46±118.06 ngml)(324.76±133.65 ngml)(p<0.05)

PCSO-524 
 
  PCSO-524 
 PCSO-524 
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: 
110330
250100
350200
*ผู้รับผิดชอบบทความE-mail: skumpana@gmail.com
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... Several clinical studies have assessed the effectiveness of GLMOC for OA treatment in dogs (6,15,17,20,26,27). An initial investigation by Mongkon and Soontornvipart (20) demonstrated improvements in the clinical signs in dogs with OA treated with GLMOC. ...
... An initial investigation by Mongkon and Soontornvipart (20) demonstrated improvements in the clinical signs in dogs with OA treated with GLMOC. Three comparative studies (15,17,26) assessing various nutraceuticals, including GLMOC, revealed significant improvements in the subjective and objective findings of the GLMOC-treated group, showing its superior efficacy relative to other nutraceuticals. Kwananocha et al. (17) found the most significant improvement when GLMOC was combined with carprofen. ...
... EAB-277 (Antinol Rapid ® ) is the proprietary combination of phospholipids extracted from krill oil together with lipid fractions from the Green Lipped Mussel (PCSO-524™). Several studies have shown an apparent benefit of PCSO-524 for canine OA pain (9)(10)(11)(12)(13). Krill oil, extracted from krill, a small red-colored crustacean inhabiting the Antarctic, has been suggested to have advantages over fish oil due to its higher phospholipid-bound EPA and DHA content. ...
Article
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Introduction With little to no regulation of the supplement markets and a paucity of quality information regarding clinical utility of individual marketed supplements, it is difficult for veterinarians to provide any evidence-based recommendations to owners. The current study aimed to provide clinically useful comparative efficacy data on certain marketed supplements. Methods Using a prospective, block-randomized, double-blinded, placebo-controlled design, one hundred and one pet dogs with clinical hip OA-associated pain with one side worse than the other (index limb) were randomly assigned to one of four treatment groups: Green lipped Mussel plus Krill oil extracts (Antinol® Rapid, EAB-277); Biota orientalis extracts (4CYTE™ Epiitalis® Forte); an NSAID (meloxicam); or placebo (sunflower oil). Peak vertical force (PVF, expressed as a percentage of bodyweight) of the index limb, orthopedic assessment score (OAS) and hematology and blood chemistry values were evaluated before treatment (week 0), at 2, 4 and 6 weeks during treatment. Results At 6 weeks, the changes from baseline in PVF of the index limb in the EAB-277 and meloxicam groups were significantly greater than the change in the placebo and 4CYTE™ groups, and the placebo and 4CYTE groups were not different from each other. At 6 weeks, there were significant differences between the groups for overall OAS scores with the lowest scores (least impairment) in the EAB-277 and meloxicam groups, followed by the 4CYTE group and then the placebo group. Discussion Results of this study indicate that meloxicam and EAB-277 have significant objectively measured benefits in managing OA-related pain in dogs compared to placebo, but 4CYTE does not differ from placebo.
... Table 2 details published studies for each of these nutraceuticals Green-lipped mussel (Perna canaliculus) Green-lipped mussel (GLM) is derived from a mussel native to New Zealand and their extract provides essential amino acids, glycoproteins and omega-3 fatty acids. Hielm-Björkman et al. (2009), Soontornvipart et al. (2015 and Vijarnsorn et al. (2019) all demonstrated improvements in clinical outcomes in canine OA by alleviating inflammation and increasing weight-bearing abilities. Furthermore, there has been reported improvement in limb manipulation with a reduction in pain, swelling, crepitus after treatment with GLM in OA dogs (Servet et al. 2006). ...
Article
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Osteoarthritis is a progressive degenerative disease process that affects a significant proportion of the canine population, impacting these animals' quality of life. Currently, there is no cure and treatment consists of managing the clinical signs of pain and reduced mobility. There are many treatments for canine osteoarthritis and in this review we discuss the evidence base behind non‐pharmaceutical, non‐surgical treatments of this disease. These treatments include weight management, nutraceuticals, acupuncture, physiotherapies such as therapeutic exercise, hydrotherapy as well as other therapeutic modalities including photobiomodulation therapy, electromagnetic field therapy and others.
... In addition, GSM oil and powder have shown promise as protective agents against proteoglycan and collagen degradation in animal studies. For example, GSM oil (PCSO-524) fed to dogs with OA at 5mg/kg body weight once daily reduced cartilage degradation and the release of WF6, an epitope of chondroitin sulphate; in contrast, fish oil fed at 1000 mg/dog twice daily had no significant protective effect [62]. More recently, GSM powder administrated at 5% of the diet, providing 1% of the total dietary fat and 33% of dietary protein, was shown in an obese rat model of metabolic OA to reduce both the production of C-telopeptide collagen type II (CTX-II), a biomarker of type II collagen degradation, and the severity of cartilage damage in knee joints [63]. ...
Article
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GreenshellTM mussels (GSMs), Perna canaliculus, are Aotearoa/New Zealand’s most important aquaculture species and is sold as a variety of food products worldwide. GSMs are a traditional and culturally valuable food of the Māori people. Following the development of a series of nutraceutical products (dried powders and extracted oils) by the GSM aquaculture industry in the 1960s, there has been an increased scientific interest in the clinical health benefits of GSM products. Omega-3 polyunsaturated fatty acids in GSMs have exhibited significant anti-inflammatory activity, and the clinical evidence has led to GSM powders and oils being extensively promoted as treatments for rheumatoid arthritis and osteoarthritis. This review defines the nutritional composition of GSMs and describes the sustainability of GSMs and their traditional uses. The review also details the health benefits of GSMs in clinical applications and identifies potential mechanisms and molecular pathways initiated by the various bioactive components of GSMs.
... PCSO-524 is a marine based fatty acid compound comprising of a patented extract stabilized marine lipids from the New Zealand green lipped mussel (Perna canaliculus). In dogs, it has been reported that the PCSO-524 is associated with beneficial effect outcomes in clinical OA cases (19)(20)(21)(22). ...
Article
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Introduction Glucosamine hydrochloride and chondroitin sulfate are commonly used in dogs with OA, but evidence around efficacy is mixed. This study evaluated the effectiveness of glucosamine and chondroitin sulfate, marine based fatty acid compounds (PCSO-524 and EAB-277), and carprofen for the alleviation of canine hip OA pain. This was a prospective, block-randomized, double-blinded, placebo-controlled clinical trial. Methods Seventy-five owned pet dogs with hip OA were assigned randomly into five treatment groups: PCSO-524, Glucosamine and chondroitin sulfate, EAB-277, carprofen, and Placebo (sunflower oil). Peak vertical force (PVF) and subjective orthopedic assessment scores (OAS) were evaluated before treatment (week 0), and at weeks 2, 4, and 6 during treatment. Results At week 2, the carprofen group showed a significant increase in PVF (3.14 ± 5.33; mean ± SD). After 4 weeks, the increases in PVF of the PCSO-524 (3.90 ± 3.52), EAB-277 (4.17 ± 4.94), and carprofen (3.08 ± 5.87) groups were significant, and significantly greater than placebo (0.08 ± 1.90) and glucosamine (−0.05 ± 6.34) groups. After 6 weeks, the change of PVF in the PCSO-524 (4.14 ± 4.65), EAB-277 (4.45 ± 4.23), and carprofen (4.21 ± 6.52) groups were significant and significantly higher than the placebo group (−0.33 ± 3.65). The change in PVF in the glucosamine group (1.08 ± 5.49) lay between the placebo group and the other treatment groups. The OAS did not show any significant change in any group. Discussion PCSO-524 and EAB-277, but not glucosamine/chondroitin, resulted in significant improvements in PVF from baseline after 4 weeks, and 6 weeks, and to a similar degree to that seen with carprofen.
... chacune des cinq catégories testées. La durée de suivi oscillait entre 42(Bierer & Bui, 2002) et 180 jours(Roush et al. 2010a) pour les diètes thérapeutiques enrichies en oméga-3 (ctg. 1) ; entre 28(Vijarnson et al. 2019) et 180 jours(Soontornvipart et al. 2015) pour les nutraceutiques à base d'oméga-3 (ctg. 2) ; entre 30(Stabile et al. 2019) et 150 jours(Gupta et al. 2010) pour les nutraceutiques à base de collagène (ctg. ...
Article
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Le but de cette revue systématique et métanalyse était d’examiner les évidences d’efficacité clinique analgésique des diètes enrichies et nutraceutiques testés chez des chiens arthrosiques. À partir de quatre bases de données bibliographiques électroniques, 1096 publications ont été retracées, en plus de 20 publications provenant de sources internes. Cinquante-quatre articles ont été inclus, comprenant 69 essais et permettant d’établir 9 catégories de traitement. L’évaluation d’efficacité, modulée par le niveau de qualité des essais, établit une évidence analgésique, avec effet clinique, pour les diètes enrichies et les suppléments à base d’oméga-3, ainsi que ceux à base de cannabidiol (à moindre degré). Nos analyses démontrent aussi une faible efficacité du collagène, et un non-effet marqué des nutraceutiques à base de chondroïtine – glucosamine qui nous pousse à recommander que ces derniers produits ne soient plus conseillés pour la gestion des douleurs en arthrose canine. Mots-Clés : Arthrose, Nutraceutiques, Compléments alimentaires, Diètes thérapeutiques, Douleur, Animal, Locomotion, Qualité méthodologique, Évidences scientifiques, Validation métrologique
... In dogs with a higher risk factor for OA, a diet with focus on joint health is ideal to ensure that the dietary ingredients included support the musculoskeletal system. In particular, omega 3 FAs have shown to be effective in reducing the signs and progression of OA (30)(31)(32)(33)(34)(35)(36)(37)(38), although it is important to provide adequate dosing (39). Most joint health focused diets have omega 3 FAs at varying dosing ranging from 0.59 to 10.11 g/1,000 kcal, with many brands being under 3.5 g/1,000 kcal (40). ...
Article
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The Canadian consensus guidelines on OA treatment were created from a diverse group of experts, with a strong clinical and/or academic background in treating OA in dogs. The document is a summary of the treatment recommendations made by the group, with treatments being divided into either a core or secondary recommendation. Each treatment or modality is then summarized in the context of available research based support and clinical experience, as the treatment of OA continues to be a multimodal and commonly a multidisciplinary as well as individualized approach. The guidelines aim to help clinicians by providing clear and clinically relevant information about treatment options based on COAST defined OA stages 1–4.
... It is important to note that there are in vivo canine trials which demonstrate the clinical effectiveness of Antinol in os-teoarthritis (Kwananocha et al., 2016;Mongkon & Soontornvipart, 2012;Soontornvipart et al., 2015). Further work attempting to elucidate mechanisms of action and the effects of Antinol on cartilage degradation are warranted. ...
Article
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With osteoarthritis being the most common degenerative disease in pet animals, a very broad panel of natural health products is available on the market for its management. The aim of this systematic review and meta-analysis, registered on PROSPERO (CRD42021279368), was to test for the evidence of clinical analgesia efficacy of fortified foods and nutraceuticals administered in dogs and cats affected by osteoarthritis. In four electronic bibliographic databases, 1578 publications were retrieved plus 20 additional publications from internal sources. Fifty-seven articles were included, comprising 72 trials divided into nine different categories of natural health compound. The efficacy assessment, associated to the level of quality of each trial, presented an evident clinical analgesic efficacy for omega-3-enriched diets, omega-3 supplements and cannabidiol (to a lesser degree). Our analyses showed a weak efficacy of collagen and a very marked non-effect of chondroitin-glucosamine nutraceuticals, which leads us to recommend that the latter products should no longer be recommended for pain management in canine and feline osteoarthritis.
Article
Owners often reach for over-the-counter supplements for the management of canine osteoarthritis, believing them to be natural, side effect-free options. Some may ask for your opinion as a veterinary professional, whereas others will come to you already using certain products. It is imperative to be aware of the evidence for the relevant products and to encourage the use of good quality products as the first option. The aim should be to help prevent owners of arthritic dogs wasting their money buying multiple products with little or no evidence to back up their use, to be wary of bold unsubstantiated claims for improvements or health benefits, and to ensure that supplements are not used as a sole intervention for the management of arthritic pain, as they are unlikely to have the evidence base to support this claim.
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This study aimed to determine whether swimming could improve function of osteoarthritic joints in canine hip OA. Fifty-five dogs were categorized into three groups. The OA with swimming group (OA-SW; n = 22), the healthy (non-OA; n = 18) with swimming group (H-SW), and the healthy (non-OA; n = 15) without swimming group (H-NSW). All animals were allowed to swim for a total of 8 weeks (2-day period, 3 cycles of swimming for 20 minutes, and resting period for 5 minutes in each cycle). Three ml of blood was collected every 2 weeks for evaluation of the levels of biomarkers for OA, including chondroitin sulfate epitope WF6 (CS-WF6) and hyaluronan (HA). Clinical evaluation of the OA-SW group found that most parameters showed improvement (P < 0.01) at week 8 compared to pretreatment, while pain on palpation was improved (P < 0.01) at week 6. The relative level of serum CS-WF6 in the OA-SW group was found to be significantly different (P < 0.01) at weeks 6 and 8 compared with the preexercise. The levels of serum HA of the H-SW group in weeks 2-8 were significantly (P < 0.01) higher than preexercise. Conclusion, swimming over 2-day period, 8 weeks continually, can improve the function of OA joint.
Conference Paper
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A developed force platform system, composed of a force sensing system, a data acquisition system and a data analysis program was used to measure the weight distributed on each paw of 25 dogs when they were standing on the platform. The system was first tested, to ensure the accuracy of the detected weight distribution, using standard weights, by placing 3 different shapes of weight, with results of less than 3% error. The animal tests were then performed using healthy and abnormal dogs varying from 2 kg to 40 kg randomly chosen and physically examined by veterinarians. The dogs were grouped into 3 healthy groups and 3 abnormal groups according to their size. The obtained results show that for healthy dogs, regardless of the size, the average force ratios from hind to fore limbs was about 63:37 and the average left:right ratios was close to 50:50 with less than a 3.2% difference between left and right limbs for both fore limbs and hind limbs. For abnormal dogs, the fore:hind ratios are not consistent ranging from 51:49 to 75:25 and the average left:right ratios are not close to 50:50 with differences between left and right limbs varying from 2.2-49%.
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Food supplemented with fish oil improves clinical signs and weight bearing in dogs with osteoarthritis (OA). Determine whether increasing the amount of fish oil in food provides additional symptomatic improvements in OA. One hundred and seventy-seven client-owned dogs with stable chronic OA of the hip or stifle. Prospective, randomized clinical trial using pet dogs. Dogs were randomly assigned to receive the baseline therapeutic food (0.8% eicosopentanoic acid [EPA] + docosahexaenoic acid [DHA]) or experimental foods containing approximately 2- and 3-fold higher EPA+DHA concentrations. Both veterinarians and owners were blinded as to which food the dog received. On days 0, 21, 45, and 90, serum fatty acid concentrations were measured and veterinarians assessed the severity of 5 clinical signs of OA. At the end of the study (day 90), veterinarians scored overall arthritic condition and progression of arthritis based on their clinical signs and an owner interview. Serum concentrations of EPA and DHA rose in parallel with food concentrations. For 2 of 5 clinical signs (lameness and weight bearing) and for overall arthritic condition and progression of arthritis, there was a significant improvement between the baseline and 3X EPA+DHA foods (P=.04, .03, .001, .0008, respectively) but not between the baseline and the 2X EPA+DHA foods. Increasing the amount of fish oil beyond that in the baseline food results in dose-dependent increases in serum EPA and DHA concentrations and modest improvements in the clinical signs of OA in pet dogs.
Article
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To determine the effects of feeding a diet supplemented with fish oil omega-3 fatty acids on carprofen dosage in dogs with osteoarthritis. Randomized, controlled, multisite clinical trial. 131 client-owned dogs with stable chronic osteoarthritis examined at 33 privately owned veterinary hospitals in the United States. In all dogs, the dosage of carprofen was standardized over a 3-week period to approximately 4.4 mg/kg/d (2 mg/lb/d), PO. Dogs were then randomly assigned to receive a food supplemented with fish oil omega-3 fatty acids or a control food with low omega-3 fatty acid content, and 3, 6, 9, and 12 weeks later, investigators made decisions regarding increasing or decreasing the carprofen dosage on the basis of investigator assessments of 5 clinical signs and owner assessments of 15 signs. Linear regression analysis indicated that over the 12-week study period, carprofen dosage decreased significantly faster among dogs fed the supplemented diet than among dogs fed the control diet. The distribution of changes in carprofen dosage for dogs in the control group was significantly different from the distribution of changes in carprofen dosage for dogs in the test group. Results suggested that in dogs with chronic osteoarthritis receiving carprofen because of signs of pain, feeding a diet supplemented with fish oil omega-3 fatty acids may allow for a reduction in carprofen dosage.
Article
The clinical outcome of PCSO-524 application in the treatment of canine osteoarthritis and spinal disorder was studied at the Small Animal Teaching Hospital, Chulalongkorn University. Eighty-four dogs were included in our study. Thirty-one dogs showed signs of osteoarthritis (OA) in both hip joints and shoulder joints; 33 dogs had OA in stifle joints from cranial cruciate ligament rupture; and 20 dogs had neurological signs of the cauda equina syndrome. All affected dogs were treated by 50 mg/ 10 kg of PCSO-524, PO for twelve weeks. Neurological grading, lameness scores and neurological examinations were evaluated before and after the administration of PCSO-524 for two and four weeks. Radiographic examinations were taken before and after the administration of PCSO-524 for four weeks. The results revealed that a large percentage of dogs experienced improvements in clinical lameness and owner preference although only a few dogs had better radiographic findings. Some of the dogs showed worse radiographic findings, whereas the clinical signs improved. Although the percentages of the improved clinical lameness between the two OA patient groups were high, but were not statistically and significantly different, the radiographic OA findings improved more in patients that had OA in the hip and shoulder joints than in patients that had OA in the stifle joints.
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Arthritis is a chronic inflammatory disease, lacking an adequate therapeutic treatment with minimal side effects. Therapy has traditionally involved the use of non-steroidal anti-inflammatory drugs which are often accompanied by severe side effects. Clinical and animal studies have demonstrated oils rich in marine derived omega-3 polyunsaturated fatty acids (n-3 PUFA) can reduce the production of eicosanoids and cytokines associated with the inflammatory response and can reduce lipid peroxidation (1, 2). Past research has shown that the lipids of the NZGLM possess equal or greater anti-inflammatory activity than regular n-3 PUFA rich fish oils (3). The aim of this study was to compare the efficacy of the NZGLM oil in comparison with a regular fish oil rich in n-3 PUFA, in reducing markers of inflammation and cardiovascular disease risk factors. This was a double blind, randomised, parallel study, with a six week dietary intervention and a two week washout period following supplementation. Twenty eight healthy subjects were randomly assigned to consume either 2 mL/day of the NZGLM oil containing 241 mg n-3 PUFA or 2 mL/day of fish oil containing 181 mg n-3 PUFA. Subjects gave fasting blood samples at day 0, day 21, 42 and 56. Dietary restrictions were implemented to control the dietary intake of n-3 PUFA from other sources. Blood was analysed for neutrophil phospholipid fatty acids and serum levels of thromboxane B 2 (TXB 2). Stimulated monocyte production of prostaglandin E 2 (PGE 2), interleukin-1β (IL-1β) and tumor necrosis factor α (TNFα) were also measured. Lipid oxidation was assessed by measuring low density lipoprotein (LDL) concentration of cholesteryl esters and cholesteryl linoleate hydroperoxide (Ch18:2n-6-OOH). Plasma antioxidant status was assessed using the ferric reducing antioxidant power (FRAP) assay, tocopherol, retinol and carotenoids. Following six weeks of supplementation, both groups showed a small, but significant increase in neutrophil phospholipid content of eicosapentaenoic acid and docosahexaenoic acid (P < 0.05), a significant reduction in serum TXB 2 and a significant reduction in endotoxin stimulated monocyte production of PGE 2 and IL-1β in subjects with high baseline levels (P < 0.05). There was an increase in plasma antioxidant status in both treatment groups (P < 0.05) and a trend to decrease LDL Ch18:2n-6-OOH and free cholesterol at day 42 compared with day 0 in both groups. These results are in agreement with past research (1–4), however the novel aspect of this study is that the dose of long chain n-3 PUFA was substantially lower than in many other studies. These data provide additional biochemical evidence that the NZGLM oil is anti-inflammatory in vivo, and could aid in reducing the symptoms associated with arthritis. It is possible that the marine oils reduced the level of these eicosanoids and cytokines by inducing a shift in cyclooxygenase and lipoxygenase substrate specificity, reducing eicosanoid and cytokine synthesis, inhibiting the expression of cell surface adhesion molecules and modulating gene transcription and peroxisome proliferator activated receptor activation. References 1. Lorenz R, Weber PC, Szimnau P, Heldwein W, Strasser T, Loeschke K. Supplementation with n-3 fatty acids from fish oil in chronic inflammatory bowel disease—a randomized, placebo-controlled, double-blind cross-over trial. J Intern Med Suppl 1989; 225: 225–32. 2. Higgins S, McCarthy SN, Corridan BM, Roche HM, Wallace JMW, O'Brien NM, et al. Measurement of free cholesterol, cholesteryl esters and cholesteryl linoleate hydroperoxide in copper-oxidised low density lipoprotein in healthy volunteers supplemented with a low dose of n-3 polyunsaturated fatty acids. Nutrition Research 2000; 20: 1091–1102. 3. Whitehouse MW, Macrides TA, Kalafatis N, Betts WH, Haynes DR, Broadbent J. Anti-inflammatory activity of a lipid fraction (Lyprinol) from the N.Z. green-lipped mussel. Inflammopharmacology 1997; 5: 237–246. 4. Kesavulu MM, Kameswararao B, Apparao C, Kumar EG, Harinarayan CV. Effect of omega-3 fatty acids on lipid peroxidation and antioxidant enzyme status in type 2 diabetic patients. Diabetes Metab 2002; 28: 20–6.
Article
Various treatments of osteoarthritis (OA) have been described, including use of nutraceuticals. To review systematically the literature about the effects of nutraceuticals on clinical signs of pain or abnormal locomotion in horses, dogs, and cats, and to discuss methodological aspects of trials and systematic reviews. A systematic search of controlled trials evaluating the impact of nutraceuticals on OA in horses, dogs, and cats was performed, using Medline, CAB Abstracts, and Google Scholar. Scientific evidence was evaluated by means of criteria proposed by the Food and Drug Administration (FDA), and a scoring system adapted from both the CONsolidated Standards of Reporting Trials (CONSORT) statement and recommendations for assessing trials by the Center of Evidence Based Medicine of Oxford. Twenty-two papers were selected and reviewed, with 5 studies performed in horses, 16 in dogs, and 1 in cats. The strength of evidence was low for all nutraceuticals except for omega-3 fatty acid in dogs. There were limited numbers of rigorous randomized controlled trials and of participants in clinical trials. The evidence of efficacy of nutraceuticals is poor, with the exception of diets supplemented with omega-3 fatty acids in dogs. Greater access to systematic reviews must be part of the objectives of the veterinary science in the future. Their reporting would be improved by internationally agreed-upon criteria for standards and guidelines.