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Topic:Osteoarthritis

Osteoarthritis (OA) in horses is a degenerative joint disease characterized by the progressive deterioration of articular cartilage, subchondral bone changes, and synovial inflammation. This condition can result in pain, reduced mobility, and impaired performance in affected animals. Osteoarthritis is commonly observed in athletic horses due to repetitive joint stress, but it can also occur in older horses as part of the natural aging process. Diagnosis typically involves clinical examination, imaging techniques such as radiography or MRI, and sometimes synovial fluid analysis. Management strategies focus on alleviating pain, reducing inflammation, and slowing disease progression through pharmacological treatments, physical therapy, and sometimes surgical interventions. This page compiles peer-reviewed research studies and scholarly articles that explore the pathophysiology, diagnosis, and management of osteoarthritis in equine patients.
Plasma concentration of insulin-like growth factor I (IGF-I) in growing Ardenner horses suffering from juvenile digital degenerative osteoarthropathy.
Veterinary research communications    January 9, 2007   Volume 31, Issue 2 185-195 doi: 10.1007/s11259-006-3385-2
Lejeune JP, Franck T, Gangl M, Schneider N, Michaux C, Deby-Dupont G, Serteyn D.Degenerative osteoarthropathy resulting in a reduced active lifespan was observed in Ardenner horses. In the context of joint biology, insulin-like growth factor I (IGF-I) is a potential candidate to affect the anabolism of cartilage matrix molecules. A group of 30 Ardenner horses reared under standardized conditions from weaning were evaluated periodically from 15 to 28 months of age to detect the early manifestations of the disease. At the end of this period, horses were classified in two pathological groups related to the degree of interphalangeal degenerative osteoarthropathy based on clin...
Severe acute inflammatory reaction (SAIR) of the fetlock joint after intraarticular hyaluronate injection in a horse.
Veterinary and comparative orthopaedics and traumatology : V.C.O.T    December 5, 2006   Volume 19, Issue 4 236-238 
Kuemmerle JM, Uhlig H, Kofler J.Hyaluronate (HA) was administered by intra-articular injection to a 13-year-old Haflinger mare for treatment of metacarpophalangeal osteoarthritis. Ten hours after the injection, a severe inflammatory reaction developed in the treated joint. While awaiting results of synovial fluid analysis, treatment for iatrogenic infectious arthritis was initiated, but the analysis did not confirm sepsis. Clinical signs improved significantly following systemic non-steroidal anti-inflammatory medication and the horse was discharged three days later. Following an intravenous hyaluronate injection, four days ...
Cartilage oligomeric matrix protein and hyaluronan levels in synovial fluid from horses with osteoarthritis of the tarsometatarsal joint compared to a control population.
Equine veterinary journal    November 28, 2006   Volume 38, Issue 6 502-507 doi: 10.2746/042516406x156073
Taylor SE, Weaver MP, Pitsillides AA, Wheeler BT, Wheeler-Jones CP, Shaw DJ, Smith RK.Quantification of cartilage oligomeric matrix protein (COMP) levels within synovial fluid from the tarsometatarsal joint has not previously been reported and an effective synovial fluid marker would allow monitoring of disease progression and treatment. Objective: To quantify levels of COMP and hyaluronan (HA) in synovial fluid from the tarsometatarsal joint, identify differences in levels from horses with osteoarthritis (OA) of the tarsometatarsal joint compared to a control population and to correlate levels with radiographic changes in horses with OA. Methods: Synovial fluid was collected f...
Proximal interphalangeal joint arthrodesis using a combination plate-screw technique in 53 horses (1994-2003).
Equine veterinary journal    November 28, 2006   Volume 38, Issue 6 538-542 doi: 10.2746/042516406x154840
Knox PM, Watkins JP.A method for proximal interphalangeal joint (PIP joint) arthrodesis that provides a stable fixation and minimal duration of cast support is evaluated retrospectively. Objective: Evaluate the clinical use of a combined plate-screw method for PIP joint arthrodesis in a large number of horses. Methods: The records of 53 horses undergoing PIP joint arthrodesis were reviewed. Arthrodesis was performed with a dorsally placed 3-, 4- or 5-hole narrow dynamic compression plate (DCP) with 2 transarticular cortex screws placed in lag fashion either side of the plate. Subject details, clinical presentatio...
Fungal osteomyelitis of the axial border of the proximal sesamoid bones in a horse.
Journal of the American Veterinary Medical Association    November 17, 2006   Volume 229, Issue 10 1607-1611 doi: 10.2460/javma.229.10.1607
Sherman KM, Myhre GD, Heymann EI.A 12-year-old Standardbred gelding was referred for swelling of the right metacarpophalangeal joint. Results: Ultrasonography of the right metacarpal area revealed hypoechoic areas in the right digital sheath and metacarpophalangeal joint consistent with synovial effusion. Radiography of the right metacarpophalangeal joint revealed lysis of the axial border of the proximal sesamoid bones. Aspergillus fumigatus was detected on fungal culture of synovial fluid. Results: Regional limb perfusion (150 mg of amikacin in 60 mL of saline [0.9% NaCl] solution perfused for 30 minutes) was performed 2 an...
Do the matrix degrading enzymes cathepsins B and D increase following a high intensity exercise regime?
Osteoarthritis and cartilage    October 19, 2006   Volume 15, Issue 3 343-349 doi: 10.1016/j.joca.2006.08.014
Bowe EA, Murray RC, Jeffcott LB, Davies ME.It has been shown by others that levels of matrix degrading enzymes are increased in osteoarthritis (OA) and so are proposed to be involved in the aetiopathogenesis of the disease, including exercise-associated OA. Therefore we hypothesised that cathepsin B and cathepsin D were increased in cartilage samples previously shown to have early stage OA from 2-year-old Thoroughbred horses, euthanased for reasons other than this study, that had a history of 19-week high intensity exercise (n=6) compared to age and sex-matched horses with a history of low intensity exercise (n=6). Methods: Cartilage s...
In vitro heterogeneity of osteogenic cell populations at various equine skeletal sites.
Canadian journal of veterinary research = Revue canadienne de recherche veterinaire    October 18, 2006   Volume 70, Issue 4 277-284 
McD○ LA, Anderson GI, Wright GM, Ryan DA.Bone cell cultures were evaluated to determine if osteogenic cell populations at different skeletal sites in the horse are heterogeneous. Osteogenic cells were isolated from cortical and cancellous bone in vitro by an explant culture method. Subcultured cells were induced to differentiate into bone-forming osteoblasts. The osteoblast phenotype was confirmed by immunohistochemical testing for osteocalcin and substantiated by positive staining of cells for alkaline phosphatase and the matrix materials collagen and glycosaminoglycans. Bone nodules were stained by the von Kossa method and counted....
Transcriptional and proteolytic regulation of the insulin-like growth factor-I system of equine articular chondrocytes by recombinant equine interleukin-1beta.
Journal of cellular physiology    August 10, 2006   Volume 209, Issue 2 542-550 doi: 10.1002/jcp.20762
Porter RM, Akers RM, Howard RD, Forsten-Williams K.Interleukin-1 (IL-1) and insulin-like growth factor-I (IGF-I), which have opposing effects on matrix metabolism within articular cartilage, are thought to play prominent roles in the pathogenesis of osteoarthritis. To better understand the link between these anabolic (IGF-I) and catabolic (IL-1) stimuli, we examined exogenous IL-1 regulation of the IGF-I signaling system of articular chondrocytes (ACs). Equine ACs from non-arthritic stifle joints were expanded in monolayer culture, encapsulated for 10 days in alginate beads, and stimulated as high-density monolayers with recombinant equine IL-...
Urine cartilage oligomeric matrix protein (COMP) measurement is useful in discriminating the osteoarthritic Thoroughbreds.
Osteoarthritis and cartilage    August 8, 2006   Volume 14, Issue 11 1174-1180 doi: 10.1016/j.joca.2006.04.017
Misumi K, Tagami M, Kamimura T, Miyakoshi D, Helal IE, Arai K, Fujiki M.To quantify the urinary concentration of cartilage oligomeric matrix protein (COMP), and to evaluate the relationship between urinary COMP concentration and the catabolic activity of synovial fluid (SF) in diseased horses. Methods: COMP in horse urine was detected by immunoblotting with a monoclonal antibody (mAb; 14G4) raised against equine COMP from articular cartilage. Urine and serum samples were obtained from 83 Thoroughbred horses with aseptic joint diseases (AJD, 79 horses) or septic joint diseases (SJD, four horses) at the time of anesthesia induction, and samples of SF were obtained d...
Evidence for functional ATP-sensitive (K(ATP)) potassium channels in human and equine articular chondrocytes.
Osteoarthritis and cartilage    August 7, 2006   Volume 15, Issue 1 1-8 doi: 10.1016/j.joca.2006.06.017
Mobasheri A, Gent TC, Nash AI, Womack MD, Moskaluk CA, Barrett-Jolley R.Chondrocytes are highly sensitive to variations in extracellular glucose and oxygen levels in the extracellular matrix. As such, they must possess a number of mechanisms to detect and respond to alterations in the metabolic state of cartilage. In other organs such as the pancreas, heart and brain, such detection is partly mediated by a family of potassium channels known as K(ATP) (adenosine 5'-triphosphate-sensitive potassium) channels. Here we investigate whether chondrocytes too express functional K(ATP) channels, which might, potentially, serve to couple metabolic state with cell activity. ...
Gross, histologic, and gene expression characteristics of osteoarthritic articular cartilage of the metacarpal condyle of horses.
American journal of veterinary research    August 3, 2006   Volume 67, Issue 8 1299-1306 doi: 10.2460/ajvr.67.8.1299
Smith KJ, Bertone AL, Weisbrode SE, Radmacher M.To identify patterns and correlations of gross, histologic, and gene expression characteristics of articular cartilage from horses with osteoarthritis. Methods: 10 clinically normal horses and 11 horses with osteoarthritis of the metacarpal condyles. Methods: Metacarpophalangeal joints were opened and digitally photographed, and gross lesions were scored and quantified. Representative cartilage specimens were stained for histologic scoring. Total RNA from dorsal and palmar articular surfaces was processed on an equine gene expression microarray. Results: Histologic scores were greater in both ...
Nitrite and nitrotyrosine concentrations in articular cartilage, subchondral bone, and trabecular bone of normal juvenile, normal adult, and osteoarthritic adult equine metacarpophalangeal joints.
The Journal of rheumatology    August 2, 2006   Volume 33, Issue 8 1662-1667 
van der Harst M, Bull S, Brama PA, Barneveld AB, van Weeren PR, van de Lest C.Osteoarthritis (OA) is a chronic debilitating joint disorder in which the importance of inflammation is increasingly recognized. In advanced cases, both the articular cartilage and the underlying bony layers are affected, but the exact sequence of events and their localization in the initial phase of pathogenesis remain uncertain. We measured nitric oxide (NO) end products in tissue layers that constitute the bearing surface of the joint, as possible indicators of physiological and pathological processes. Methods: Nitrite as a measure for NO and nitrotyrosine was measured in articular cartilag...
Mapping of donor and recipient site properties for osteochondral graft reconstruction of subchondral cystic lesions in the equine stifle joint.
Equine veterinary journal    July 27, 2006   Volume 38, Issue 4 330-336 doi: 10.2746/042516406777749254
Changoor A, Hurtig MB, Runciman RJ, Quesnel AJ, Dickey JP, Lowerison M.To improve osteochondral graft reconstruction of subchondral cystic lesions in the medial and lateral femoral condyles by matching the material properties of donor and recipient sites. Objective: To measure biomechanical and biochemical parameters that influence the function and healing of osteochondral grafts used to reconstruct subchondral cystic lesions. Objective: Suitable donor sites are available within the stifle joint for reconstructing the femoral condyles, despite considerable regional property variation. Methods: Fifty-six osteochondral cores were harvested from 6 distal femurs for ...
Signaling through the small G-protein Cdc42 is involved in insulin-like growth factor-I resistance in aging articular chondrocytes.
Journal of orthopaedic research : official publication of the Orthopaedic Research Society    June 17, 2006   Volume 24, Issue 8 1765-1772 doi: 10.1002/jor.20185
Fortier LA, Miller BJ.During aging, chondrocytes become unresponsive to insulin-like growth factor-I (IGF-I). This study examined the role of Cdc42 (cell-division-cycle 42) in IGF-I signaling during aging. Experiments were performed using cartilage and chondrocytes isolated from horses ages 1 day-25 years. Northern analysis was used to examine expression of the small GTPases Cdc42, Rac, and RhoA. Western analysis was utilized to assess total Cdc42 (GTP + GDP-bound); active, GTP-Cdc42 was assessed using a pulldown assay with Western analysis. GTP-Cdc42 was also measured following IGF-I treatment. Gene expression for...
Microscopic change in macroscopically normal equine cartilage from osteoarthritic joints.
Connective tissue research    June 7, 2006   Volume 47, Issue 2 92-101 doi: 10.1080/03008200600584165
Weaver RE, Sharif M, Livingston LA, Andrews KL, Fuller CJ.The objective of this study was to assess whether macroscopically normal articular cartilage taken from joints containing focal osteoarthritic lesions is histologically similar to articular cartilage taken from macroscopically normal joints. Metacarpophalangeal, proximal interphalangeal, and distal interphalangeal joints were obtained from 10 horses following euthanasia. Gross articular cartilage damage was scored and the cartilage assigned to one of two groups: (1) macroscopically normal cartilage from normal joints (control) and (2) macroscopically normal cartilage from diseased joints in wh...
Assessment of the catabolic effects of interleukin-1beta on proteoglycan metabolism in equine cartilage cocultured with synoviocytes.
American journal of veterinary research    June 3, 2006   Volume 67, Issue 6 957-962 doi: 10.2460/ajvr.67.6.957
Gregg AJ, Fortier LA, Mohammed HO, Mayr KG, Miller BJ, Haupt JL.To evaluate the effects of interleukin (IL)-1beta on proteoglycan metabolism in equine cartilage explants when cultured in the presence of synoviocytes. Methods: Samples of cartilage and synovium collected from the femoropatellar joints of three 2- to 3-year-old horses. Methods: 3 experimental groups were established: cartilage explants only, synoviocytes only, and cartilage explants-synoviocytes in coculture. In each group, samples were cultured with or without IL-1beta (10 ng/mL) for 96 hours. Glycosaminoglycan (GAG) content of cartilage and medium samples was measured by use of a spectropho...
Fourier transform infrared imaging spectroscopy investigations in the pathogenesis and repair of cartilage.
Biochimica et biophysica acta    May 23, 2006   Volume 1758, Issue 7 934-941 doi: 10.1016/j.bbamem.2006.05.014
Bi X, Yang X, Bostrom MP, Camacho NP.Significant complications in the management of osteoarthritis (OA) are the inability to identify early cartilage changes during the development of the disease, and the lack of techniques to evaluate the tissue response to therapeutic and tissue engineering interventions. In recent studies several spectroscopic parameters have been elucidated by Fourier transform infrared imaging spectroscopy (FT-IRIS) that enable evaluation of molecular and compositional changes in human cartilage with progressively severe OA, and in repair cartilage from animal models. FT-IRIS permits evaluation of early-stag...
Inhibition of caspase-9 reduces chondrocyte apoptosis and proteoglycan loss following mechanical trauma.
Osteoarthritis and cartilage    May 12, 2006   Volume 14, Issue 10 1002-1010 doi: 10.1016/j.joca.2006.03.012
Huser CA, Peacock M, Davies ME.Chondrocyte death, a notable feature of osteoarthritis, may play a role in the initiation of cartilage degeneration. The present study was aimed at uncovering the nature and involvement of cell death in the initiation of cartilage degeneration induced by mechanical trauma. Methods: Articular cartilage discs obtained from healthy skeletally mature horses were subjected to a single-impact load (500 g from 50 mm) using a simple drop-tower device and cultured in vitro for 48 h. Chondrocyte death was examined using two independent methods: transmission electron microscopy and caspase-3 activity ass...
Use of intra-articular administration of ethyl alcohol for arthrodesis of the tarsometatarsal joint in healthy horses.
American journal of veterinary research    May 3, 2006   Volume 67, Issue 5 850-857 doi: 10.2460/ajvr.67.5.850
Shoemaker RW, Allen AL, Richardson CE, Wilson DG.To evaluate the efficacy and safety of intra-articular administration of ethyl alcohol for arthrodesis of tarsometatarsal joints in horses. Methods: 8 healthy female horses without lameness or radiographic evidence of tarsal joint osteoarthritis. Methods: In each horse, 1 tarsometatarsal joint was treated with 4 mL of 70% ethyl alcohol and the opposite joint was treated with 4 mL of 95% ethyl alcohol. Lameness examinations were performed daily for 2 weeks, followed by monthly evaluations for the duration of the 12-month study. Radiographic evaluations of both tarsi were performed 1 month after...
In situ and ex vivo evaluation of an arthroscopic indentation instrument to estimate the health status of articular cartilage in the equine metacarpophalangeal joint.
Veterinary surgery : VS    April 26, 2006   Volume 35, Issue 3 259-266 doi: 10.1111/j.1532-950X.2006.00136.x
Brommer H, Laasanen MS, Brama PA, van Weeren PR, Helminen HJ, Jurvelin JS.To evaluate an arthroscopic indentation instrument (Artscan 200) for assessment of the health status of equine articular cartilage. Methods: In vitro experiment using equine isolated proximal phalanx (P1) specimens. Methods: P1 specimens from 39 horses (aged 1.5-22 years). Methods: Reproducibility was tested by determination of the coefficient of variation (CV). Dynamic modulus and cartilage degeneration index (CDI) values were measured at 2 predefined sites (site 1, joint margin; site 2, joint center) to assess the accuracy and to evaluate the relation with surface integrity. Results: CV was ...
Unilateral ataxia and head tilt in a 7-year-old Thoroughbred stallion. Temporohyoid osteoarthropathy.
Australian veterinary journal    April 25, 2006   Volume 84, Issue 4 136-142 doi: 10.1111/j.1751-0813.2006.tb13397.x
Hughes KJ, Hodgson DR.The research article discusses the case of a 7-year-old Thoroughbred stallion presenting symptoms such as ataxia, a leftward head tilt and a cloudy left eye, revealing a diagnosis of temporohyoid […]
Arthrodesis of the talocalcaneal joint for the treatment of two horses with talocalcaneal osteoarthritis.
Veterinary and comparative orthopaedics and traumatology : V.C.O.T    April 6, 2006   Volume 18, Issue 1 7-12 
Pauwels FE, Adams SB, Blevins WB.Two horses with lameness due to tolocalcaneal osteoarthritis that failed to respond to conservative management were treated by tolocalcaneal arthrodesis using cortex screws placed in lag fashion. The affected joint of one horse was arthrodesed by compressing and stabilizing the medial facet of the joint with three screws. In the second horse, the medial and lateral facets of the affected tolocalcaneal joint were each compressed and stabilized with two screws. The lameness of both horses improved markedly following surgery.
Arthroscopically assisted arthrodesis of the distal interphalangeal joint with transarticular screws inserted through a dorsal hoof wall approach in a horse.
Journal of the American Veterinary Medical Association    March 16, 2006   Volume 228, Issue 6 909-913 doi: 10.2460/javma.228.6.909
Busschers E, Richardson DW.A 16-year-old Thoroughbred gelding was examined because of chronic right forelimb lameness. Results: On radiographs of the right front foot, the distal interphalangeal (DIP) joint space was narrow, and osteophytes and periarticular bony proliferation indicative of severe osteoarthritis were seen. Arthrodesis of the right DIP joint was recommended to improve the horse's comfort on the limb. Results: The horse was anesthetized, and palmar and dorsal arthroscopic approaches were used to remove as much of the articular cartilage as was accessible. Holes were then drilled through the dorsal aspect ...
Validation of an in vitro single-impact load model of the initiation of osteoarthritis-like changes in articular cartilage.
Journal of orthopaedic research : official publication of the Orthopaedic Research Society    March 4, 2006   Volume 24, Issue 4 725-732 doi: 10.1002/jor.20111
Huser CA, Davies ME.The objective of this study was the development and characterization of an in vitro model of the initiation of traumatic osteoarthritis (OA). Articular cartilage was obtained from seven healthy horses and from four horses diagnosed with OA. Cartilage disks were subjected to a single-impact load (500 g from 25, 50, or 100 mm) using a simple drop-tower device and cultured in vitro for up to 20 days. Cartilage sections were examined histologically to observe surface damage and proteoglycan loss. Percentage cell death was determined using TUNEL, release of glycosaminoglycans (GAG) to the medium wa...
In vivo study on the short-term effect of radiofrequency energy on chondromalacic patellar cartilage and its correlation with calcified cartilage pathology in an equine model.
Journal of orthopaedic research : official publication of the Orthopaedic Research Society    March 4, 2006   Volume 24, Issue 4 716-724 doi: 10.1002/jor.20108
Uthamanthil RK, Edwards RB, Lu Y, Manley PA, Athanasiou KA, Markel MD.Chondromalacia can cause joint pain and synovial effusion with the potential for developing into osteoarthritis. Thermal chondroplasty using radiofrequency energy (RFE) has been reported to be superior to mechanical debridement for treating chondromalacia. We compared short-term changes in biomechanical properties of articular cartilage after treatment with monopolar (mRFE) or bipolar RFE (bRFE) or mechanical debridement (MD) on experimentally created grade II chondromalacia patellae. Chondromalacia patellae was created arthroscopically in both patellae of 15 ponies. Ten months after surgery, ...
Characterization of experimentally induced post-traumatic osteoarthritis in the medial femorotibial joint of horses.
American journal of veterinary research    March 2, 2006   Volume 67, Issue 3 433-447 doi: 10.2460/ajvr.67.3.433
Bolam CJ, Hurtig MB, Cruz A, McEwen BJ.To study osteoarthritis in the equine medial femorotibial (MFT) joint after a single traumatic injury. Methods: 10 mature horses. Methods: In vitro explant cultures were used to determine injury threshold for stifle joint cartilage. Contusive impacts were applied to the medial femoral condyle (MFC), and horses were followed for 84 (n = 5) and 180 days (5). Synovial fluid samples were collected every 14 days for determination of sulphated glycosaminoglycan (sGAG) concentrations. Radiographic and lameness evaluations were performed. Gross and histologic descriptions, and immunohistochemistry, ca...
Therapy for osteoarthritis in the horse – how do we know that it works?
Veterinary journal (London, England : 1997)    January 24, 2006   Volume 171, Issue 1 9-10 doi: 10.1016/j.tvjl.2005.02.003
Clegg PD.No abstract available
Medical treatment of osteoarthritis in the horse – a review.
Veterinary journal (London, England : 1997)    January 24, 2006   Volume 171, Issue 1 51-69 doi: 10.1016/j.tvjl.2004.07.008
Goodrich LR, Nixon AJ.The medical treatment of osteoarthritis (OA) in the horse is one of the most utilized therapeutic regimens in the equine practice. It is important to understand the anatomy of synovial joints and the pathophysiology of the disease process to treat OA adequately. Once a thorough understanding of the disease process is comprehended the proper combination of systemic nonsteroidal anti-inflammatory drugs (NSAIDs), intraarticular steroids, viscosupplementation and chondroprotectants can be used to treat the disease and inhibit further progression of degenerative changes to the cartilage surface. Th...
Osteochondral graft fixation using a bioresorbable bone cement.
Journal of biomechanics    January 4, 2006   Volume 39, Issue 15 2887-2892 doi: 10.1016/j.jbiomech.2005.10.007
Changoor A, Hurtig MB, John Runciman R.Multiple osteochondral grafts can be used to resurface large joint defects in both humans and horses. In humans, immediate postoperative weight bearing can be prevented, however in the equine, it is unavoidable. Early weight bearing can create detrimental graft micromotion. The aim of this study was to investigate the role of a bioresorbable cement in improving the initial stability of multiple osteochondral graft repairs of large subchondral cystic lesions in the horse. Configurations employed for filling a 20mm diameter cylindrical defect included: (A) twelve 4.5mm diameter grafts with cemen...
Effects of glucosamine and chondroitin sulfate on mediators of osteoarthritis in cultured equine chondrocytes stimulated by use of recombinant equine interleukin-1beta.
American journal of veterinary research    December 13, 2005   Volume 66, Issue 11 1861-1869 doi: 10.2460/ajvr.2005.66.1861
Neil KM, Orth MW, Coussens PM, Chan PS, Caron JP.To determine whether glucosamine and chondroitin sulfate (CS) at concentrations approximating those achieved in plasma by oral administration would influence gene expression of selected mediators of osteoarthritis in cytokine-stimulated equine articular chondrocytes. Methods: Samples of grossly normal articular cartilage obtained from the metacarpophalangeal joint of 13 horses. Methods: Equine chondrocytes in pellet culture were stimulated with a subsaturating dose of recombinant equine interleukin (reIL)-1beta. Effects of prior incubation with glucosamine (2.5 to 10.0 microg/mL) and CS (5.0 t...
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