| 1. |
- Corin, Antonia, et al.
(författare)
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Computed tomography evaluation of intra-articular mineralization in feline stifle joints
- 2016
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Ingår i: Veterinary Radiology and Ultrasound. - 1058-8183 .- 1740-8261. ; 57, s. 658-658
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- COMPUTEDTOMOGRAPHYEVALUATIONOFINTRA-ARTICULARMINERALIZATIONINFELINESTIFLEJOINTSA.Corin,C.Ley,A.Leijon,C.J.Ley.FromtheDepartmentofClinicalSciences(Corin,Ley)andDepartmentofBiomedicalSciencesandVeterinaryPublicHealth,SwedishUniversityofAgriculturalSciences,UppsalaSE-75007,Sweden(Ley,Leijon).Introduction/Purpose:Intra-articularmineralization(IAM)isacommonradiographicfndingincatstifle.TheetiologyofIAMremainsunknown,althoughseveralstudieshaveshownacorrela-tionwithosteoarthritis(OA).Theaimsofthisstudywereto(a)investigatecorrela-ionsbetweenIAMandtheparametersage,sex,catsize,andsesamoidvolumes;(b)investigatepossiblecorrelationsbetweenIAMandOAcartilagelesions;(c)comparethesizeofIAMincomputedtomography(CT)imagesandradiographsofthesamestifle.Methods:Rightstifljointsfrom28cats(16MN,9FN,3F),age1-23years(mean9.9),weight2.1-7.3kg(mean3.9)thatdiedforreasonsunrelatedtothestudywereexaminedpostmortemwithCTandradiography,followedbymacroscopicandmicroscopicevaluationofjointtissues.Femurvolume,IAMvolume,andsesamoidmineralizedtissuevolumesweremeasuredinCTimages.Intra-articularmineralizationareawasmeasuredinmediolateralprojectionradiographsandcategorizedaccordingtoapublishedstudy.1Allmeasurementsweredonebyoneauthor(C.J.L.).ThearticularcartilagewasgradedforpresenceofOAlesionsbytwoauthors(C.L.,A.L.)usingconsensusandwithlightmicroscopyhistology.OsteoarthritisgradeswerecomparedwiththepresenceandvolumeofIAMinCTimages.Regressionanalysis,t-tests,andFisherexacttestswereusedandvaluesofP<0.05wereconsideredsignificantResults:In13of28jointsIAMweredetectedandallexceptonewerelocatedwithinthemedialmeniscus.Whenmeasuredinradiographs11of13IAMweresmall(<2.25mm2),twowereintermediate,andnoIAMwerelarge(>6.25mm2).Osteoarthritiswasdetectedin26jointsandofthese13hadminimalOA,11hadmildOA,andtwohadmoderateOA.NosignificancorrelationwasfoundbetweenIAMandgradeofOAcartilagelesions,femurvolume,lateralfabellavolume,poplitealsesamoidvolume,patellavolume,sex,orageofthecats.Themedialfabellawasmineralizedin16cats,eightofwhichhadIAM.ThemedialfabellawassignificantllargerincatswithIAM.AreaofIAMinradiographshadsignificancorrelationswithCTvolumemeasurements.Discussion/Conclusions:Intra-articularmineralizationswerenotaconsistentfindininstifljointswithminimal,mild,andmoderateOAcartilagelesions.SmallmineralizationsinthefelinemedialmeniscusmaydevelopforreasonsotherthanOAandsmallIAMareunlikelytobeareliableindicationoffelinestiflOA.ThereasonforcatswithIAMhavinglargermineralizedmedialfabellaisnotclear.ItseemsreasonabletousemeasurementsfrommediolateralprojectionradiographstoestimateIAMsizeinfelinestifljoints.References:1.VossK,etal.JFelineMedSurg2015;Epubaheadofprint.
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| 2. |
- Leijon, Alexandra, et al.
(författare)
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Cartilage lesions in feline stifle joints – Associations with articular mineralizations and implications for osteoarthritis
- 2017
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Ingår i: Research in Veterinary Science. - : Elsevier BV. - 0034-5288 .- 1532-2661. ; 114, s. 186-193
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Tidskriftsartikel (refereegranskat)abstract
- Feline stifle osteoarthritis (OA) is common, however little is known about the early stages of the disease. Furthermore, the importance of small articular mineralizations (AMs) in feline stifle OA is controversial. This study aimed to describe microscopic articular cartilage lesions and to investigate associations between cartilage lesions and AMs, synovitis, osteochondral junction findings and subchondral bone sclerosis. Stifles of 29 cats, aged 1-23 years and euthanized for reasons other than stifle disease, were examined. Osteochondral tissue and synovial membrane changes were histologically evaluated. Computed tomography and radiography were used for evaluation of AMs. Global cartilage scores (GCS, n = 28) were summarized and joints assigned a histologic OA grade. Minimal to mild histologic OA was seen in 24/28 joints. In 27/29 joints tibial cartilage lesions were seen, whereas femoral lesions were only seen in two joints. Articular mineralizations were detected in 13/29 joints, 11 were small and 12 were located entirely within the medial meniscus. There was no association between GCS and presence or volumes of AMs. However, higher GCS was associated with synovitis (P = 0.001) and age (P < 0.0005). Presence of subchondral bone sclerosis (P < 0.0005) and disruption of the calcified cartilage or tidemark (P < 0.0005) were associated with cartilage lesions. We conclude that the tibial articular cartilage is a common location for histologic OA lesions in cats. Synovitis and changes in the subchondral bone and calcified cartilage may be important in the pathogenesis of feline stifle OA, whereas small AMs likely represent incidental findings.
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| 3. |
- Leijon, Alexandra, et al.
(författare)
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Morphological changes of osteoarthritis in feline stifle joints and associations to intra-articular mineralization
- 2017
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Ingår i: Journal of Comparative Pathology. - 0021-9975 .- 1532-3129. ; 156, s. 83-83
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- MORPHOLOGICAL CHANGES OF OSTEOARTHRITIS IN FELINE STIFLE JOINTS AND ASSOCIATIONS WITH INTRAARTICULAR MINERALIZATION A. Leijon*, C.J. Ley y , A. Corin y and C. Ley* *Department of Biomedical Sciences and Veterinary Public Health and y Department of Clinical Sciences, Swedish University of Agricultural Sciences, Sweden Introduction: Osteoarthritis (OA) is common in cats. However, there are no detailed histological descriptions of feline stifle OA. Intra-articular mineralization (IAM) is commonly detected in feline stifle radiographs, but the association between small IAMs and feline OA is unclear. The purpose of this study was to describe OA lesions in feline stifle joints and to investigate associations between articular cartilage lesions, synovitis and IAMs. Materials and Methods: The right stifle joints from 29 cats (age 1e23 years, median 9) were examined for IAM using computed tomography and radiography, followed by macro- and microscopical evaluation of joint tissues. Articular cartilage lesions and synovitis were graded histologically. Cartilage lesions were summarized into global joint scores (GJS, n 5 28). Associations between cartilage lesions, synovitis and IAMs were determined. Results: The most frequent location of cartilage lesions was the tibia (27/29 joints), followed by the patella (14/28 joints). The majority of cartilage lesions were low grade. Femoral cartilage lesions (2/29 joints) were only seen in joints with severe tibial cartilage lesions. Synovitis was present in 13/29 joints and always low grade. IAMs were detected in 13 joints, 11 were classified as small. Neither GJS nor synovitis scores were associated with IAMs; however, increased GJS was associated with synovitis (P 5 0.001). Conclusions: OA lesions in the articular cartilage were common and associated with synovitis. Tibial cartilage may represent the most common site for detection of early morphological cartilage changes of feline stifle OA. Lack of association between GJS and IAMs suggests that small IAMs are incidental findings in OAaffected joints.
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| 4. |
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| 5. |
- Ley, Cecilia, et al.
(författare)
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Acetabular margin changes in feline hip joints-Implications for radiologic diagnosis and development of osteoarthritis
- 2021
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Ingår i: Research in Veterinary Science. - : Elsevier BV. - 0034-5288 .- 1532-2661. ; 137, s. 243-251
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Tidskriftsartikel (refereegranskat)abstract
- The development and early morphological features of feline hip osteoarthritis (OA) are largely unknown. Tears in the acetabular labrum and at the chondrolabral transition zone are suggested to be important in the pathogenesis of human hip OA, but in cats such lesions have not been described. We investigated associations between computed tomography (CT)-detected joint changes and microscopic articular cartilage lesions, the distribution of detected changes, and histologically evaluated the acetabular margin (AM) in hip joints from 20 cats. Histologic evaluation was undertaken on at least one joint from each cat. CT-detected joint changes and articular cartilage lesions were graded and the histological appearance of CT-detected osteophytes evaluated. The majority of CTdetected lesions and cartilage lesions were mild. Whole-joint CT scores and AM osteophyte CT scores showed moderate to strong correlation with cartilage scores. The odds were higher for presence of CT-detected osteophytes in craniodorsal, cranial, cranioventral, ventral and dorsal AM regions. Peripheral acetabular regions showed higher cartilage lesion grades than central regions. Tears, seen as fissures/clefts, in labral and perilabral tissues were common. CT-detected AM osteophytes morphologically presented as pointed sclerotic bone, spurshaped bone or rounded chondro-osteophytes. The results suggest that CT is a valuable tool for diagnosing early feline hip OA. CT-detected osteophytes showed variable histologic morphologies, which may implicate different disease mechanisms and/or disease stages. Tears in the AM could represent an early event in feline hip OA and this warrants further investigation.
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| 6. |
- Ley, Charles, et al.
(författare)
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Computed tomography is superior to radiography for detection of feline elbow osteoarthritis
- 2021
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Ingår i: Research in Veterinary Science. - : Elsevier BV. - 0034-5288 .- 1532-2661. ; 140, s. 6-17
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Tidskriftsartikel (refereegranskat)abstract
- Elbow osteoarthritis (OA) is common in cats and radiography is typically used for diagnosis. However computed tomography (CT), with its multiplanar three-dimensional characteristics, could have significant advantages for assessment of OA compared to radiography, particularly early in the disease process. The study objectives were to compare radiography and CT to histologic OA changes, investigate the stage of OA that radiography and CT detect, and search for specific changes in CT images strongly predictive for feline elbow OA. Right elbows from 29 cats were evaluated by radiography and CT, and articular cartilage lesions graded histologically and macroscopically. Three further joints were sampled to specifically evaluate the morphology of the anconeal process. Macroscopic, radiographic and CT OA diagnosis were compared to the reference standard histologic OA that was divided into mild, moderate and severe. Osteophytic spurs on the lateral margin of the anconeal process could be reliably measured in CT images (intra-class correlation 0.79) and when >= 0.5 mm had high sensitivity for moderate/severe histologic OA, moderate sensitivity for mild histologic OA and high specificity for all stages of OA. In moderate/severe histologic OA both radiography and CT subjective OA diagnosis had moderate to very high sensitivity. However, in mild histologic OA CT grading had low sensitivity and radiography did not detect OA. In conclusion, CT of the feline elbow including measurement of osteophytes on the anconeal process lateral margin is superior to radiography for OA detection and should be considered for OA diagnosis, particularly when mild OA changes are of interest.
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| 7. |
- Ley, Cecilia, et al.
(författare)
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Evaluation of body fat content and osteoarthritis in cats using computed tomography – a novel approach using whole-body imaging
- 2015
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Ingår i: Acta Veterinaria Scandinavica Supplementum. - 0065-1699. ; 57, s. 9-9
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Evaluation of body fat content and osteoarthritis in cats using computed tomography - a novel approach using whole-body imaging Cecilia Ley1*, Charles J Ley2 1Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Uppsala, Sweden; 2Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden E-mail: cecilia.ley@slu.se Acta Veterinaria Scandinavica 2015, 57(Suppl 1):P7 Introduction: Development of whole-body multidetector computed tomography (MDCT) methods have the potential to allow investigations into relations between feline osteoarthritis (OA) and obesity. In one MDCT examination all joints in an animal and the total body fat content can be evaluated. However, studies investigating the correlation between presence of joint lesions detected by MDCT and macroscopic evidence of OA are lacking. Objectives: The aims of the study were to evaluate whole-body MDCT for the diagnosis of feline OA, and to utilize a method for whole-body MDCT-based quantitative fat content determination. Methods: MDCT images from 30 cats were evaluated for joint lesions and fat percentages (fat%) were calculated for 14 cats. Body condition scores (BCS) were determined using a nine-grade scale. The shoulder, elbow, antebrachiocarpal, hip, stifle and tarsocrural joints were macroscopically evaluated for presence of cartilage lesions. Associations between MDCT-detected lesions and macroscopic cartilage lesions were investigated, and the correlation between MDCT-fat% and BCS determined. Results: Significant associations between MDCT-detected lesions and macroscopic cartilage lesions were detected in the shoulder (p=0.0002), elbow (p=0.009), and tarsocrural (p=0.004) joints. MDCT estimates of fat% ranged from 13.4-48.6% (median 34%) and the BCS ranged from 2- 8 (median 5). There was significant correlation between fat% and the BCS (p=0.006). Conclusion: Whole-body MDCT is useful for predicting macroscopic cartilage lesions in feline shoulder, elbow and tarsocrural joints and for determination of body fat content. These methods may be valuable for future studies of feline OA and investigations into the possible influence of obesity on OA development.
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| 8. |
- Ley, Cecilia, et al.
(författare)
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Falciform fat:femur length ratio provides a novel method for objective postmortem estimation of total body fat in overweight and obese cats
- 2022
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Ingår i: Journal of Veterinary Diagnostic Investigation. - : SAGE Publications. - 1040-6387 .- 1943-4936. ; 34, s. 237-245
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Tidskriftsartikel (refereegranskat)abstract
- Determination of the nutritional condition, including estimation of amounts of total body fat (tBF), at routine postmortem examination of cats is typically based on subjective visual assessment. Subjective assessment may result in uncertainties regarding degree of overweight, and objective methods that provide a numerical value reflecting the tBF could be valuable to accurately judge excess body fat. We investigated if the falciform fat pad weight (FFPW) was correlated to tBF and could be used to detect overweight and obesity in cats. The FFPW and the femur length (FL) were recorded at postmortem examination in 54 cats and the FFPW:FL ratio (FFR) calculated. Each cat was additionally assigned to a fat category (FC) according to subjective assessment. Computed tomography was used to determine tBF as the body fat percentage (%BF), the body fat volume (BFV), and BFV normalized to animal size (nBFV) in 39 cats. There was strong correlation between the FFPW and the BFV (r = 0.888) and between the FFR and the nBFV (r = 0.897). The correlation between the nBFV and %BF was very strong (r = 0.974). Using a lower FFR cutoff value of 3.5 for obesity and 1.6 for overweight, there was a discrepancy in FC between using the FFR and subjective assessment in 6 of 54 cats (11%). We conclude that the FFPW increases proportionally with tBF and that the FFR provides a method for objective tBF estimation. We suggest introducing the FFR to feline postmortem examination protocols as an objective estimate of tBF.
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| 9. |
- Strage, Emma, et al.
(författare)
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Homeostasis model assessment, serum insulin and their relation to body fat in cats
- 2021
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Ingår i: BMC Veterinary Research. - : Springer Science and Business Media LLC. - 1746-6148. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundObesity is associated with insulin resistance (IR) and considered a risk factor for diabetes mellitus (DM) in cats. It has been proposed that homeostasis model assessment (HOMA-IR), which is the product of fasting serum insulin (mU/L) and glucose (mmol/L) divided by 22.5, can be used to indicate IR. The objectives of this study were threefold: (i) to evaluate associations between body fat, fasting insulin, and HOMA-IR, (ii) to determine population-based reference interval of HOMA-IR in healthy lean cats, and (iii) to evaluate biological variation of HOMA-IR and fasting insulin in cats.Results150 cats were grouped as lean or overweight based on body condition score and in 68 of the cats body fat percentage (BF%) was estimated by computed tomography. Fasting serum insulin and glucose concentrations were analysed. Statistical differences in HOMA-IR and insulin between overweight or lean cats were evaluated using Wilcoxon rank-sum test. Robust method with Box-Cox transformation was used for calculating HOMA-IR reference interval in healthy lean cats. Relations between BF% and HOMA-IR and insulin were evaluated by regression analysis. Restricted maximum likelihood ratio was used to calculate indices of biological variation of HOMA-IR and insulin in seven cats.There were significant differences between groups with overweight cats (n = 77) having higher HOMA-IR (p < 0.0001) and insulin (p = 0.0002) than lean cats (n = 73). Reference interval for HOMA-IR in lean cats was 0.1–3.0. HOMA-IR and fasting insulin concentrations showed similar significant positive association with BF% (p = 0.0010 and p = 0.0017, respectively). Within-animal coefficient of variation of HOMA-IR and insulin was 51% and 49%, respectively.ConclusionsHOMA-IR and fasting insulin higher in overweight than lean cats and correlate to BF%. The established population-based reference interval for HOMA-IR as well as the indices of biological variation for HOMA-IR and fasting insulin may be used when interpreting HOMA-IR and fasting insulin in cats. Further studies are needed to evaluate if HOMA-IR or fasting insulin is useful for identifying cats at risk of developing DM.
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| 10. |
- Tengstrand, Sofia, et al.
(författare)
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Mystery of fatal 'staggering disease' unravelled: novel rustrela virus causes severe meningoencephalomyelitis in domestic cats
- 2023
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- ‘Staggering disease’ is a neurological disease entity considered a threat to European domestic cats (Felis catus) for almost five decades. However, its aetiology has remained obscure. Rustrela virus (RusV), a relative of rubella virus, has recently been shown to be associated with encephalitis in a broad range of mammalian hosts. Here, we report the detection of RusV RNA and antigen by metagenomic sequencing, RT-qPCR, in-situ hybridization and immunohistochemistry in brain tissues of 27 out of 29 cats with non-suppurative meningoencephalomyelitis and clinical signs compatible with’staggering disease’ from Sweden, Austria, and Germany, but not in non-affected control cats. Screening of possible reservoir hosts in Sweden revealed RusV infection in wood mice (Apodemus sylvaticus). Our work indicates that RusV is the long-sought cause of feline ‘staggering disease’. Given its reported broad host spectrum and considerable geographic range, RusV may be the aetiological agent of neuropathologies in further mammals, possibly even including humans.
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| 11. |
- Blomström, Anne-Lie, et al.
(författare)
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Astrovirus as a possible cause of congenital tremor type AII in piglets?
- 2014
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Ingår i: Acta Veterinaria Scandinavica. - : Springer Science and Business Media LLC. - 0044-605X .- 1751-0147. ; 56
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Tidskriftsartikel (refereegranskat)abstract
- Background: Congenital tremor is associated with demyelination of the brain and spinal cord and is clinically noted as outbreaks of trembling and shaking in newborn piglets during a limited time-period. Six forms of the disease have been described, where form AII may be caused by an, as yet, unidentified viral infection. This study aimed to investigate the presence of astrovirus and circovirus by sequencing and polymerase chain reaction (PCR) analysis and by relating the findings to the occurrence of disease and lesions in the brain, in 4-6 days-old piglets obtained from a clinical outbreak of congenital tremor.Results: In piglets with congenital tremor, there were mild to moderate vacuolar changes of the white matter in the cerebrum, brain stem and cerebellum. In healthy piglets, less conspicuous vacuolar changes were detected. One healthy and one diseased piglet were positive for porcine circovirus type 2. The nested pan-PCR showed the presence of astrovirus in at least one brain region in all piglets and by sequencing, two different porcine astrovirus lineages were identified.Conclusions: The results do not support previous studies identifying porcine circovirus type 2 as the cause of congenital tremor. The demonstration of astrovirus in the brain of piglets suffering from congenital tremor is interesting. However, astrovirus was demonstrated in both healthy and diseased individuals and therefore, further studies are warranted to determine the possible involvement of astrovirus in the pathogenesis of congenital tremor in pigs.
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| 12. |
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| 13. |
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| 14. |
- Hedenqvist, Patricia, et al.
(författare)
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Carprofen neither reduces postoperative facial expression scores in rabbits treated with buprenorphine nor alters long term bone formation after maxillary sinus grafting
- 2016
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Ingår i: Research in Veterinary Science. - : Elsevier BV. - 0034-5288 .- 1532-2661. ; 107, s. 123-131
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Tidskriftsartikel (refereegranskat)abstract
- In connection with bilateral maxillary sinus augmentation, the acute effects of the nonsteroidal anti-inflammatory drug carprofen on facial expressions and long-term effects on bone formation were evaluated in 18 male New Zealand White rabbits. A 10 x 10 mm bone window was drilled in the maxilla, the sinus membrane elevated and a titanium mini-implant inserted. One of two test materials was randomly inserted unilaterally and bovine bone chips (control) on the contralateral side in the created space. Rabbits were randomly allocated to receive buprenorphine plus carprofen (n = 9) or buprenorphine plus saline (n = 9) postoperatively. Buprenorphine was administered subcutaneously every 6 h for 3 days in a tapered dose (0.05-0.01 mg/kg) and carprofen (5 mg/kg) or saline administered subcutaneously 1 h before, and daily for 4 days postoperatively. To assess pain, clinical examination, body weight recording and scoring of facial expressions from photos taken before, and 6-13 h after surgery were performed. Twelve weeks after surgery the rabbits were euthanized and sections of maxillary bones and sinuses were analysed with histomorphometry and by qualitative histology. Carprofen had no effect on mean facial expression scores, which increased from 0.0 to 3.6 (carprofen) and 43 (saline), of a maximum of 8.0. Neither did carprofen have an effect on bone formation or implant incorporation, whereas the test materials had. In conclusion, treatment with 5 mg/kg carprofen once daily for 5 days did not reduce facial expression scores after maxillary sinus augmentation in buprenorphine treated rabbits and did not affect long term bone formation.
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| 15. |
- Hedenqvist, Patricia, et al.
(författare)
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The effect of housing environment on bone healing in a critical radius defect in New Zealand White rabbits
- 2020
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 15:5
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Tidskriftsartikel (refereegranskat)abstract
- In animal studies on bone healing, the effect of housing space and physical activity are seldom taken into account. Bone formation was evaluated in New Zealand White rabbits (mean ± SEM BW: 3.9 ± 0.11 kg) with a critical bone defect after 12 weeks of rehabilitation in pair-housing in 3 m2 large floor pens (Floor, n = 10) or standard single housing in 0.43 m2 cages (Cage, n = 10). In the randomised full-factorial study, a bone replica of calcium phosphate cement (CPC, n = 10) or autologous bone (AB, n = 10) was implanted in the unilateral 20 mm radius defect. Post-mortem, the oxidative capacity was measured by citrate synthase (CS) activity in M. quadriceps and the defect filling volume and density evaluated by microcomputer tomography (μ-CT). Histology sections were evaluated by subjective scoring and histomorphometry. Fourteen rabbits remained until the end of the study. Group Floor (n = 7; 3 CPC + 4 AB) had a higher CS activity and a larger bone defect filling volume and lower density by μ-CT measurements than group Cage (n = 7; 3 CPC + 4 AB). Three out of four rabbits in AB-Floor presented fusion of the defect with reorganisation of trabecular bone, whereas three of four in AB-Cage showed areas of incomplete healing. Floor rabbits had a higher score of bony fusion between the radius and ulna than Cage rabbits. There were no differences between groups in histomorphometry. The study found that a larger housing space increased physical activity and promoted bone formation. © 2020 Hedenqvist et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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| 16. |
- Ley, Cecilia, et al.
(författare)
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Effects of high mobility group box protein-1, interleukin-1 beta, and interleukin-6 on cartilage matrix metabolism in three-dimensional equine chondrocyte cultures
- 2011
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Ingår i: Connective Tissue Research. - : Informa UK Limited. - 0300-8207 .- 1607-8438. ; 52, s. 290-300
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Tidskriftsartikel (refereegranskat)abstract
- The effects of high mobility group box protein (HMGB)-1, interleukin (IL)-1 beta, and IL-6 on equine articular chondrocytes were investigated, with emphasis on detecting differences between anatomical sites exposed to different loading in vivo, using three-dimensional (3D) cell cultures established with chondrocytes from dorsal radial facet (DRF, highly loaded) and palmar condyle (PC, less loaded) of the third carpal bone (C3). Expression of important genes involved in cartilage metabolism, presence of glycosaminoglycans and cartilage oligomeric matrix protein (COMP) in pellets, and concentrations of matrix metalloproteinase (MMP)-13 and aggrecan epitope CS 846 were evaluated. Compared to controls, IL-1 beta treatment increased gene expression of versican, matrix-degrading enzymes, and tissue inhibitor of metalloproteinase (TIMP)-1, and decreased aggrecan and collagen type I and type II expression. In addition, IL-1 beta-treated pellets showed decreased safranin O staining and increased COMP immunostaining and MMP-13 concentrations in culture supernatants. Effects of IL-6 and HMGB-1 on gene expression were variable, although upregulation of Sry-related high-mobility group box 9 (Sox9) was often present and statistically increased in HMGB-1-treated pellets. Response to cytokines rarely differed between DRF and PC pellets. Thus, site-associated cartilage deterioration in equine carpal osteoarthritis (OA) is not explained by topographically different responses to inflammatory mediators. Differences in gene expressions of structural matrix proteins in untreated DRF and PC pellets were noted in the youngest horses, which may indicate differences in the chondrocytes potential to produce matrix in vivo. Overall, a strong catabolic response was induced by IL-1 beta, whereas slight anabolic effects were induced by IL-6 and HMGB-1.
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| 17. |
- Ley, Cecilia, et al.
(författare)
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Effects of high mobility group box protein-1, interleukin-1β, and interleukin-6 on cartilage matrix metabolism in three-dimensional equine chondrocyte cultures.
- 2011
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Ingår i: Connective tissue research. - : Informa UK Limited. - 1607-8438 .- 0300-8207. ; 52:4, s. 290-300
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Tidskriftsartikel (refereegranskat)abstract
- The effects of high mobility group box protein (HMGB)-1, interleukin (IL)-1β, and IL-6 on equine articular chondrocytes were investigated, with emphasis on detecting differences between anatomical sites exposed to different loading in vivo, using three-dimensional (3D) cell cultures established with chondrocytes from dorsal radial facet (DRF, highly loaded) and palmar condyle (PC, less loaded) of the third carpal bone (C3). Expression of important genes involved in cartilage metabolism, presence of glycosaminoglycans and cartilage oligomeric matrix protein (COMP) in pellets, and concentrations of matrix metalloproteinase (MMP)-13 and aggrecan epitope CS 846 were evaluated. Compared to controls, IL-1β treatment increased gene expression of versican, matrix-degrading enzymes, and tissue inhibitor of metalloproteinase (TIMP)-1, and decreased aggrecan and collagen type I and type II expression. In addition, IL-1β-treated pellets showed decreased safranin O staining and increased COMP immunostaining and MMP-13 concentrations in culture supernatants. Effects of IL-6 and HMGB-1 on gene expression were variable, although upregulation of Sry-related high-mobility group box 9 (Sox9) was often present and statistically increased in HMGB-1-treated pellets. Response to cytokines rarely differed between DRF and PC pellets. Thus, site-associated cartilage deterioration in equine carpal osteoarthritis (OA) is not explained by topographically different responses to inflammatory mediators. Differences in gene expressions of structural matrix proteins in untreated DRF and PC pellets were noted in the youngest horses, which may indicate differences in the chondrocytes potential to produce matrix in vivo. Overall, a strong catabolic response was induced by IL-1β, whereas slight anabolic effects were induced by IL-6 and HMGB-1.
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| 18. |
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| 19. |
- Ley, Cecilia
(författare)
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Inflammatory response in equine joints : studies on proinflammatory cytokines in diseased joints and chondrocyte cultures
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Proinflammatory cytokines mediate inflammatory responses as well as regulate tissue metabolism. Thus, they may provide a link between inflammation and other pathologic findings seen in equine joint disease. The aims of this thesis were to gain a deeper understanding of the development of chondral pathology in equine osteoarthritis (OA) by obtaining increased knowledge of inflammatory processes in the joint, and to investigate proinflammatory cytokines as markers of joint pathology. Measurements of interleukin (IL)-6 and tumour necrosis factor (TNF) activities in synovial fluid from clinical cases of carpal joint disease revealed increased concentrations of bioactive IL-6 in joints with osteochondral fragments (OCF). Immunohistochemical staining for IL-6 and high mobility group box protein (HMGB)-1 in tissues from diseased carpal and fetlock joints identified both OCF and synovial membranes as cellular sources of IL-6 and extracellular/cytoplasmic HMBG-1. Histological assessment of synovial membrane biopsies from immunostained joints showed increased grade of synovitis in diseased compared to healthy joints. The effects of IL-6, IL-1β and HMGB-1 on chondrocyte metabolism was studied in vitro, and focused on gene expression analyses. A catabolic response to IL-1β was detected, whereas the response to IL-6 and HMGB-1 was varied but indicated promotion of cartilage formation. Analyses of the ultrastructural immunolocalisation of HMGB-1 in IL-1β and IL-6 treated pellets, showed a trend for decreased nuclear/cytoplasmic ratio, and increased extracellular matrix density of HMGB-1 after IL-6 treatment. Theses studies gained insight to presence of TNF, IL-6 and HMGB-1 in equine joints, and indicated an increased inflammatory response in joints with OCF. The difference in metabolic response of chondrocytes to IL-1β versus IL-6 or HMGB-1 in vitro, and differences in HMGB-1 translocation after IL-1β and IL-6 treatment suggest that the outcome of cartilage pathology in equine joint disease may relate to the individual contributions of cytokine activity and cytokine interactions.
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| 20. |
- Ley, Cecilia, et al.
(författare)
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Interleukin-6 and high mobility group box protein-1 in synovial membranes and osteochondral fragments in equine osteoarthritis
- 2009
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Ingår i: Research in Veterinary Science. - : Elsevier BV. - 0034-5288 .- 1532-2661. ; 86:3, s. 490-497
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Tidskriftsartikel (refereegranskat)abstract
- Cytokine production in synovial membranes (SM) and osteochondral fragments (OCF) may influence the development of equine osteoarthritis (OA). In this study, the presence of interleukin (IL)-6 and cytoplasmic and extracellular high mobility group box protein (HMGB)-1 in SM and osteochondral tissue from healthy and diseased equine joints was investigated by immunohistochemistry. Additionally, microscopic synovitis was graded. IL-6 was commonly found in SM cells and in chondrocytes in uncalcified cartilage of OCF, whereas little staining was detected in healthy cartilage. Cytoplasmic and/or extracellular HMGB-1 was widespread only in SM from diseased joints, and also detected in OCF in areas of cartilage damage, fibrous repair tissue, and tidemark reduplication. Joints with OCF and cartilage lesions (without OCF) showed significantly higher median synovitis scores than healthy joints (p=0.013 and p=0.042, respectively). The study identifies OCF as a source of inflammatory mediators in equine OA, as shown by the presence of IL-6 and extracellular HMGB-1 in the fragment. Based upon HMGB-1 release in SM and OCF, further studies to investigate possible involvement of HMGB-1 in the pathogenesis of OA are warranted.
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| 21. |
- Ley, Cecilia, et al.
(författare)
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Interleukin-6 and tumour necrosis factor in synovial fluid from horses with carpal joint pathology
- 2007
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Ingår i: Journal of Veterinary Medicine A. - : Wiley. - 0931-184X .- 1439-0442. ; 54:7, s. 346-351
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Tidskriftsartikel (refereegranskat)abstract
- The carpal joints are common sites of traumatic arthritis and osteoarthritis (OA) in athletic horses. The pro-inflammatory cytokines interleukin (IL)-6 and tumour necrosis factor (TNF) may be of great importance in the development of intra-articular lesions. The aim of the present study was to investigate possible associations between synovial fluid levels of bioactive IL-6 and TNF and different types of joint lesions seen in traumatic arthritis and OA. Synovial fluid was collected from horses with carpal lameness immediately before arthroscopic surgery. Articular cartilage, synovial membranes and intra-articular ligaments were assessed macroscopically at arthroscopy. Synovial fluid levels of IL-6 and TNF were determined by bioassays, and the cytokine levels between different grades of morphologic changes in each type of assessed tissue were compared. The highest levels of IL-6 were detected in joints with chip fractures. All joints with chip fractures also showed some degree of synovitis. Tumour necrosis factor bioactivity was low and not associated with any joint lesion. Hence, TNF is not useful as a biomarker indicating a specific joint lesion in equine traumatic arthritis or OA. We conclude that a dramatic increase of IL-6 in synovial fluid indicates the presence of osteochondral fragmentation, although low or undetectable levels of IL-6 do not exclude chip fractures. The role of IL-6 in the disease process of osteochondral fragmentation needs further investigation.
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| 22. |
- Ley, Cecilia, et al.
(författare)
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Presence of CD3+ and CD79a+ lymphocytes in the pituitary gland of dogs at post-mortem examination
- 2020
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Ingår i: Journal of Comparative Pathology. - : Elsevier BV. - 0021-9975 .- 1532-3129. ; 176, s. 116-121
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Tidskriftsartikel (refereegranskat)abstract
- Hypophysitis has been reported occasionally in dogs, with most cases resembling primary lymphocytic hypophysitis in man. Although it is generally assumed that lymphocytes are not present normally in the canine pituitary gland, few studies have investigated this hypothesis. However, lymphocytes are recognized in the pituitary gland of people and horses without signs of pituitary disease. It is unknown to what degree lymphocyte infiltration of the pituitary gland might occur as an incidental finding in dogs. The aim of the present study was to investigate the presence and distribution of lymphocytes in the pituitary gland of dogs without clinical suspicion of pituitary disease. Twenty dogs were subjected to routine necropsy examination. Formalin-fixed and paraffin wax-embedded sections of pituitary were stained with haematoxylin and eosin (HE) or subjected to immunohistochemistry (IHC) using primary antibodies specific for the T-cell marker CD3 and the B-cell marker CD79a. The number of CD3(+) and CD79a(+) cells per area unit (CPA) was determined for different pituitary regions. Two dogs had extensive neoplastic lesions in the pituitary gland and were excluded from analysis. In the remaining 18 dogs, occasional scattered CD3(+) cells were found in the pituitary gland. There was a significant difference in CD3(+) CPA between pituitary regions (P = 0.001). The highest CD3(+) CPA was found in the pars tuberalis (median 41.3 cells/mm(2), interquartile range 20.9-50.5 cells/mm(2)). In six of the 18 dogs (33%), CD79a(+) cells were detected in small number (median total cell number 0 cells/section, interquartile range 0-1.0 cells/section). This study shows that T cell, and fewer B cells, may be found in the pituitary gland of dogs without clinical suspicion of pituitary disease. Regional difference in T-cell density, with the highest CD3(+) CPA in the pars tuberalis, may imply regional immunoregulatory functions in the canine pituitary gland. (C) 2020 The Authors. Published by Elsevier Ltd.
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| 23. |
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| 24. |
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| 25. |
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| 26. |
- Löfgren, Maria, et al.
(författare)
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Cell and matrix modulation in prenatal and postnatal equine growth cartilage, zones of Ranvier and articular cartilage
- 2014
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Ingår i: Journal of Anatomy. - : Wiley. - 0021-8782 .- 1469-7580. ; 225:5, s. 548-568
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Tidskriftsartikel (refereegranskat)abstract
- Formation of synovial joints includes phenotypic changes of the chondrocytes and the organisation of their extracellular matrix is regulated by different factors and signalling pathways. Increased knowledge of the normal processes involved in joint development may be used to identify similar regulatory mechanisms during pathological conditions in the joint. Samples of the distal radius were collected from prenatal and postnatal equine growth plates, zones of Ranvier and articular cartilage with the aim of identifying Notch signalling components and cells with stem cell-like characteristics and to follow changes in matrix protein localisation during joint development. The localisation of the Notch signalling components Notch1, Delta4, Hes1, Notch dysregulating protein epidermal growth factor-like domain 7 (EGFL7), the stem cell-indicating factor Stro-1 and the matrix molecules cartilage oligomeric matrix protein (COMP), fibromodulin, matrilin-1 and chondroadherin were studied using immunohistochemistry. Spatial changes in protein localisations during cartilage maturation were observed for Notch signalling components and matrix molecules, with increased pericellular localisation indicating new synthesis and involvement of these proteins in the formation of the joint. However, it was not possible to characterise the phenotype of the chondrocytes based on their surrounding matrix during normal chondrogenesis. The zone of Ranvier was identified in all horses and characterised as an area expressing Stro-1, EGFL7 and chondroadherin with an absence of COMP and Notch signalling. Stro-1 was also present in cells close to the perichondrium, in the articular cartilage and in the fetal resting zone, indicating stem cell-like characteristics of these cells. The presence of stem cells in the articular cartilage will be of importance for the repair of damaged cartilage. Perivascular chondrocytes and hypertrophic cells of the cartilage bone interface displayed positive staining for EGFL7, which is a novel finding and suggests a role of EGFL7 in the vascular infiltration of growth cartilage.
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| 27. |
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| 28. |
- Mellgren, Torbjörn, 1986-, et al.
(författare)
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Guided bone tissue regeneration using a hollow calcium phosphate based implant in a critical size rabbit radius defect
- 2021
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Ingår i: Biomedical Materials. - : Institute of Physics Publishing (IOPP). - 1748-6041 .- 1748-605X. ; 16:3
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Tidskriftsartikel (refereegranskat)abstract
- Long bone fractures are common and sometimes difficult to treat. Autologous bone (AB), bovine bone and calcium phosphates are used to stimulate bone growth with varying results. In the present study, a calcium phosphate cement (CPC) that previously showed promising grafting capabilities was evaluated for the first time in a long bone defect. A radius defect of 20 mm was created in 20 rabbits. The defect was filled by either a hollow CPC implant that had been manufactured as a replica of a rabbit radius through indirect 3D printing, or by particulate AB as control. Defect filling and bone formation was evaluated after 12 weeks by combining micro computed tomography (mu CT) and scoring of 3D images, together with histomorphometry and histology. The mu CT and histomorphometric evaluations showed a similar amount of filling of the defect (combining graft and bone) between the CPC and AB group, but the scoring of 3D images showed that the filling in the CPC group was significantly larger. Histologically the AB graft could not be distinguished from the new bone. The AB treated defects were found to be composed of more bone than the CPC group, including reorganised cancellous and cortical bone. Both the CPC and AB material was associated with new bone formation, also in the middle of the defect, which could result in closing of the otherwise critically sized gap. This study shows the potential for an indirectly 3D printed implant in guided bone regeneration in critically sized long bone defects.
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| 29. |
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| 30. |
- Miller, Andrea, et al.
(författare)
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First identification of Echinococcus multilocularis in rodent intermediate hosts in Sweden
- 2016
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Ingår i: International Journal for Parasitology. - : Elsevier BV. - 0020-7519 .- 1879-0135. ; 5, s. 56-63
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Tidskriftsartikel (refereegranskat)abstract
- Echinococcus multilocularis is a zoonotic tapeworm with a sylvatic lifecycle and an expanding range in Europe. Monitoring efforts following its first identification in 2011 in Sweden have focused on the parasite's definitive host, the red fox (Vulpes vulpes). However, identifying rodent intermediate hosts is important to recognize opportunities for parasite transmission. During 2013-2015, livers from a total of 1566 rodents from four regions in Sweden were examined for E.multilocularis metacestode lesions. Species identity of suspect parasite lesions was confirmed by PCR and sequencing. E.multilocularis positive lesions >6mm in diameter were also examined histologically. One Microtus agrestis out of 187 (0.5%, 95%CI: 0-2.9%), 8/439 (1.8%, 95%CI: 0.8-3.6%) Arvicola amphibius, 0/655 (0%, 95%CI: 0-0.6%) Myodes glareolus, and 0/285 (0%, 95%CI: 0-1.3%) Apodemus spp. contained E.multilocularis metacestode lesions. Presence of protoscoleces was confirmed in the infected M.agrestis and in three of eight infected A.amphibius. Six of the nine positive rodents were captured from the same field. This is the first report of E.multilocularis in intermediate hosts in Sweden. The cluster of positive rodents in one field shows that local parasite prevalence can be high in Sweden despite overall low national prevalence in foxes (<0.1%). The presence of protoscoleces in infected M.agrestis and A.amphibius indicate these species can serve as competent intermediate hosts in Sweden. However, their relative importance for E.multilocularis transmission in the Swedish environment is not yet possible to assess. In contrast, the negative findings in all M.glareolus and Apodemus spp. suggest that these species are of no importance.
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| 31. |
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| 32. |
- Skiöldebrand, Eva, et al.
(författare)
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Serotonin-evoked cytosolic Ca2+ release and opioid receptor expression are upregulated in articular cartilage chondrocytes from osteoarthritic joints in horses
- 2019
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Ingår i: Veterinary and Animal Science. - : Elsevier BV. - 2451-943X. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Osteoarthritis is a pain-associated progressive disease and pain mediators, such as opioid receptors, expressed in articular cartilage could represent novel therapeutic targets. Acute and chronic stages of OA indicate different metabolic abilities of the chondrocytes depending on inflammatory state. This study aimed to investigate the response of healthy and osteoarthritic chondrocytes and their expression and release of pain mediators in response to acute inflammation. Interleukin-1 beta (IL-1β) and lipopolysaccharide (LPS) were used to induce an acute inflammatory response in cultured equine chondrocytes harvested from healthy joints (HC) and osteoarthritic joints (OAC), the latter representing acute exacerbation of a chronic inflammatory state. Intracellular Ca2+ release was determined after exposure to serotonin (5-hydroxytryptamine (5-HT), glutamate or ATP. Protein expression levels of F- and G-actin, representing actin rearrangement, and opioid receptors were investigated. Glutamate concentrations in culture media were measured. Cartilage was immunohistochemically stained for µ (MOR), κ (KOR), and δ (DOR) opioid receptors. Upon exposure to acute inflammatory stimuli, OAC showed increased intracellular Ca2+ release after 5-HT stimulation and increased expression of MOR and KOR. When cells were stimulated by inflammatory mediators, glutamate release was increased in both HC and OAC. Immunostaining for MOR was strong in OA cartilage, whereas KOR was less strongly expressed. DOR was not expressed by cultured HC and OAC and immunostaining of OA cartilage equivocal. We show that chondrocytes in different inflammatory stages react differently to the neurotransmitter 5-HT with respect to intracellular Ca2+ release and expression of peripheral pain mediators. Our findings suggest that opioids and neurotransmitters are important in the progression of equine OA. The inflammatory stage of OA (acute versus chronic) should be taken into consideration when therapeutic strategies are being developed. © 2019 The Author(s)
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| 33. |
- Strage, Emma, et al.
(författare)
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Insulin release from isolated cat islets of Langerhans
- 2024
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Ingår i: Domestic Animal Endocrinology. - : Elsevier. - 0739-7240 .- 1879-0054. ; 87
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Tidskriftsartikel (refereegranskat)abstract
- Feline diabetes mellitus is a common endocrine disease with increasing prevalence. It shows similarities with human type 2 diabetes and is characterized by insulin resistance and deficient insulin secretion. Moreover, cats and humans belong to the very few species that form amyloid depositions in the pancreatic islets. However, little is known about cat islet function and no studies have addressed insulin secretion from isolated islets ex vivo. The aim of this study was to establish a protocol for isolation of islets of Langerhans from pancreata of cats euthanized due to disease, and to evaluate insulin secretion responses to various physiological and pharmacological stimuli. Collagenase digestion of pancreatic tissue from 13 non-diabetic cats and two cats with diabetic ketoacidosis yielded individual islets surrounded by a layer of exocrine tissue that was reduced after two days in culture. Histological examination showed islet amyloid in pancreatic biopsies from most non-diabetic and in one diabetic cat. Islets from non-diabetic cats cultured at 5.5 mM glucose responded with increased insulin secretion to 16.7 mM glucose, 30 mM K+ and 20 µM of the sulfonylurea glipizide (2-3 times basal secretion at 3 mM glucose). The glucagon-like peptide-1 receptor agonist exendin-4 (100 nM) had no effect under basal conditions but potentiated glucose-triggered insulin release. Only one of nine islet batches from diabetic cats released detectable amounts of insulin, which was enhanced by exendin-4. Culture of islets from non-diabetic cats at 25 mM glucose impaired secretion both in response to glucose and K+ depolarization. In conclusion, we describe a procedure for isolation of islets from cat pancreas biopsies and demonstrate that isolated cat islets secrete insulin in response to glucose and antidiabetic drugs. The study provides a basis for future ex vivo studies of islet function relevant to the understanding of the pathophysiology and treatment of feline diabetes.
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| 34. |
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| 35. |
- Svala, Emilia, et al.
(författare)
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Effects of interleukin-6 and interleukin-1 beta on expression of growth differentiation factor-5 and Wnt signaling pathway genes in equine chondrocytes
- 2014
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Ingår i: American Journal of Veterinary Research. - : American Veterinary Medical Association (AVMA). - 0002-9645 .- 1943-5681. ; 75:2, s. 132-140
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Tidskriftsartikel (refereegranskat)abstract
- Objective-To determine the effects of interleukin (IL)-6 and IL-1 beta stimulation on expression of growth differentiation factor (GDF)-5 and Wnt signaling pathway genes in equine chondrocytes. Sample-Macroscopically normal articular cartilage samples from 6 horses and osteochondral fragments (OCFs) from 3 horses. Procedures-Chondrocyte pellets were prepared and cultured without stimulation or following stimulation with IL-6 or IL-1 beta for 1, 2, 12, and 48 hours; expression of GDF-5 was determined with a quantitative real-time PCR assay. Expression of genes in various signaling pathways was determined with microarrays for pellets stimulated for 1 and 2 hours. Immunohistochemical analysis was used to detect GDF-5, glycogen synthase kinase 3 beta (GSK-3 beta), and beta-catenin proteins in macroscopically normal cartilage samples and OCFs. Results-Chondrocytes stimulated with IL-6 had significantly higher GDF-5 expression within 2 hours versus unstimulated chondrocytes. Microarray analysis of Wnt signaling pathway genes indicated expression of GSK-3 beta and coiled-coil domain containing 88C increased after 1 hour and expression of beta-catenin decreased after 2 hours of IL-6 stimulation. Results of immunohistochemical detection of proteins were similar to microarray analysis results. Chondrocytes in macroscopically normal articular cartilage and OCFs had immunostaining for GDF-5. Conclusion and Clinical Relevance-Results indicated IL-6 stimulation decreased chondrocyte expression of the canonical Wnt signaling pathway transactivator beta-catenin, induced expression of inhibitors of the Wnt pathway, and increased expression of GDF-5. This suggested IL-6 may inhibit the Wnt signaling pathway with subsequent upregulation of GDF-5 expression. Anabolic extracellular matrix metabolism in OCFs may be attributable to GDF-5 expression. This information could be useful for development of cartilage repair methods.
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| 36. |
- Trbakovic, Amela, et al.
(författare)
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A new synthetic granular calcium phosphate compound induces new bone in a sinus lift rabbit model
- 2018
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Ingår i: Journal of Dentistry. - : Elsevier BV. - 0300-5712 .- 1879-176X. ; 70, s. 31-39
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Tidskriftsartikel (refereegranskat)abstract
- Objectives The aim of this study was to investigate if a synthetic granular calcium phosphate compound (CPC) and a composite bisphosphonate-linked hyaluronic acid–calcium phosphate hydrogel (HABP·CaP) induced similar or more amount of bone as bovine mineral in a modified sinus lift rabbit model. Material and methods Eighteen adult male New Zeeland White rabbits, received randomly one of the two test materials on a random side of the face, and bovine mineral as control on the contralateral side. In a sinus lift, the sinus mucosa was elevated and a titanium mini-implant was placed in the alveolar bone. Augmentation material (CPC, HABP·CaP or bovine bone) was applied in the space around the implant. The rabbits were euthanized three months after surgery and qualitative and histomorphometric evaluation were conducted. Histomorphometric evaluation included three different regions of interest (ROIs) and the bone to implant contact on each installed implant. Results Qualitative assessment (p=<.05), histomorphometric evaluations (p=<.01), and implant incorporation (p=<.05) showed that CPC and bovine mineral induced similar amount of bone and more than the HABP·CaP hydrogel. Conclusion CPC induced similar amount of bone as bovine mineral and both materials induced more bone than HABP·CaP hydrogel. Clinical significance The CPC is suggested as a synthetic alternative for augmentations in the maxillofacial area.
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| 37. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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