Objective Chondrocytes are crucial for adequate matrix balance and function. Cell proliferation and, recently, extensive apoptotic cell death have been reported in osteoarthritic (OA) cartilage. Apoptotic cell death would be an obvious central factor in the initiation and progression of OA, since there is no potential for replacing articular chondrocytes in the adult. Therefore, we studied the occurrence of apoptotic cell disintegration and cell proliferation in OA and normal articular cartilage obtained from the knees of adult donors of all ages. Methods Following immunostaining for cellular proteins as well as staining for nuclear DNA, we performed triple‐channel confocal laser scanning microscopy on thick cartilage slices to evaluate lacunar emptying and cell viability. Cell proliferation and apoptotic cell death were evaluated morphologically, by immunodetection of the proliferation‐associated Ki‐67 antigen, and by the TUNEL reaction. Results With the exception of the calcified layer, we were not able to detect any major (apoptotic or nonapoptotic) cell disintegration in normal young or aged articular knee cartilage. Single apoptotic cells were detected in OA articular knee cartilage. A significant increase in lacunar emptying was observed in late‐stage specimens with higher Mankin scores compared with age‐matched normal control cartilage specimens, but not in low‐grade lesions. A significant (but lesser) increase in empty lacunae was also observed with age in normal cartilage. Cell proliferation was rarely detected in OA cartilage samples and was not detected at all in normal cartilage samples. Conclusion Our results confirm the findings of previous studies showing that cell proliferation occurs in OA cartilage. They also show that, contrary to previous suggestions, apoptotic cell death is not a widespread phenomenon in aging or OA cartilage.

Objective. To evaluate the anabolic activity of osteoarthritic chondrocytes in situ by investigating the messenger RNA (mRNA) expression of 3 major cartilage components, type I1 collagen, aggrecan, and link protein.Methods. In situ hybridization experiments and histochemical analysis for proteoglycan content were performed on parallel sections of normal and osteoarthritic (OA) cartilage specimens.Results. Most chondrocytes in the deeper zones of OA cartilage showed an increase in mRNA expression, in particular, of type I1 collagen and to a lesser extent, aggrecan, compared with normal specimens. However, chondrocytes of the upper zone were largely negative for aggrecan or type I1 collagen mRNA. The expression of link protein mRNA was low in normal and OA specimens.Conclusion. These observations suggest that suppression of the anabolic activity of chondrocytes in the upper zones contributes to the metabolic imbalance observed in OA cartilage. Stimulation of matrix anabolism in superficial chondrocytes might be a suitable target for therapeutic intervention.The unique biomechanical properties of articular cartilage are provided by its extracellular matrix, and the failure of cartilage in joint disease is a consequence of the progressive destruction of this matrix. The extracelMar matrix of articular cartilage consists of 2 major Supported by the Deutsche Forschungsgemeinschaft (DFG Grant Ai 20/1-1).T. Aigner, MD, S. I. Vornehm, BsC, K. von der Mark, PhD: University of Erlangen-Nurnberg, Erlangen, Germany; G. Zeiler, MD: Orthopedic Hospital Wichernhaus, Rummelsberg, Schwarzenbruck, Germany; J. Dudhia, PhD, M. T. Bayliss, PhD: Kennedy Institute of Rheumatology, London, UK.Address reprint requests to T. Aigner, MD, Institute of Pathology, University of Erlangen-Nurnberg, Krankenhausstrasse 8-10, D-91054 Erlangen, Germany.Submitted for publication June 17, 1996; accepted in revised form September 3, 1996. components: the network of types 11, IX, and XI collagen (l), which provides the tensile strength and stiffness of articular cartilage, and the large aggregating proteoglycan, aggrecan, which is responsible for the osmotic swelling capacity, and thus the elasticity, of the cartilage matrix (2,3). Aggrecan associates with hyaluronic acid, and this interaction is stabilized by link protein (4), which shares homology with the hyaluronan-binding (Gl) domain of aggrecan. Other cartilage proteoglycans such as decorin, biglycan, fibromodulin, and versican may be present in the cartilage matrix in equimolar amounts, but have other important functions, such as control of collagen fibril diameter and binding of growth factors (2,5,6). Similarly, type VI collagen, which is specifically found in the pericellular matrix of articular cartilage, presumably plays a crucial role in the establishment of the microenvironment of the chondrocytes (7).In normal adult articular cartilage, the turnover of collagen fibrils is very low (8-lo), whereas a relatively high turnover rate for aggrecan has been measured (11,12). In osteoarthritic...

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Objective. The aim of this study was to evaluate the messenger RNA (mRNA) expression and distribution of the major pericellular type VI collagen in normal and osteoarthritic (OA) cartilage.Methods. Conventional and confocal laser scanning immunohistochemistry, as well as in situ hybridization experiments, were performed for all 3 collagen type VI chains in sections of normal and OA articular cartilage.Results. individual microfibrillar network in virtually all connective tissues (1-4). In hyaline articular cartilage, type V1 collagen has thus far been described in the immediate pericellular matrix (5-8), and is therefore an integral component of the chondron, the functional unit of the articular cartilage (9,lO). This local restriction is the main reason why type VI collagen represents only a small portion (<2%) of all cartilage collagens (11).The composition of the pericellular matrix of articular chondrocytes is different in many respects from that of the territorial and interterritorial cartilage matrix. Thus, besides type VI collagen, it contains increased amounts of specifically composed proteoglycans (1 2), other collagens such as types IX (13) and XI (14), and noncollagenous components (15). The function of type VI collagen in articular cartilage is still unclear, but it is likely to be different from that in other connective tissues, where it is not associated with cells. Type VI collagen has been shown to bind to integrins of the chondrocyte membrane, though the exact interaction remains unclear (16,17). Additionally, type VI collagen binds to other proteins of the pericellular matrix, such as other collagens, decorin, fibromodulin, hyaluronan, and fibronectin (18)(19)(20). Thus. type VI collagen might act as an interface between the rigid interterritorial cartilage matrix and the chondrocyte, and is presumably involved in cell anchoring as well as matrix-cell signaling (21).The hallmark of osteoarthritic (OA) cartilage degeneration is the destruction and, finally, the erosion of the extracellular cartilage matrix. This implies degradation, as well as increased synthesis, of cartilage matrix components. Most investigations so far have analyzed the biochemistry of the major components of the interterritorial cartilage matrix, and many data have accumulated about synthesis and degradation of, for example, type I1 collagen and aggrecan (22)(23)(24)(25). Much less attention has been given to the changes in the pericellular matrix and its turnover by the chondrocytes. Poole et a1

We evaluated behavioural changes in domestic cats during a short-term hospitalisation using a novel cat demeanour scoring system. Thirty-five, healthy client-owned cats admitted for neutering were enrolled. Cats were housed in a standardised cat ward for a short-term hospitalisation period (3-5 days) and demeanour scores were recorded once daily. The scoring system classified cats into one of five behavioural groupings: friendly-and-confident, friendlyand-shy, withdrawn-and-protective, withdrawn-and-aggressive, and overtly-aggressive. Total demeanour score decreased over time (P<0.001) and the demeanour category improved (P<0.001). The intra-class correlation was 0.843 (P<0.001) and kappa was 0.606 (P<0.001) suggesting good repeatability and agreement among investigators. The demeanour scoring system was effective in detecting behaviour change in healthy cats undergoing a short-term hospitalisation period. The findings suggest that healthy cats require two days to acclimatise to hospitalisation.

Goats are rarely anaesthetised; consequently, scant information is available on the efficacy of anaesthetic drugs in this species. Alfaxalone is a relatively new anaesthetic agent, of which the efficacy in goats has not yet been studied. In this study, the sedative and alfaxalone sparing effects of midazolam and butorphanol, administered alone or concomitantly, in goats were assessed. Eight clinically healthy goats, four does and four wethers, were enlisted in a randomised crossover manner to receive intramuscular sedative treatments consisting of saline 0.05 mL/kg, or midazolam 0.30 mg/kg, or butorphanol 0.10 mg/kg, or a combination of midazolam 0.30 mg/kg with butorphanol 0.10 mg/kg before intravenous induction of general anaesthesia with alfaxalone. Following induction, the goats were immediately intubated and the quality of anaesthesia and basic physiological cardiorespiratory and blood-gas parameters were assessed until the goats had recovered from anaesthesia. The degree of sedation, quality of induction and recovery were scored. When compared with saline (3.00 mg/kg), midazolam,administered alone or with butorphanol, caused a statistically significant increased level of sedation and a reduction in the amount of alfaxalone required for induction (2.00 mg/kg and 1.70 mg/kg, respectively). Butorphanol alone (2.30 mg/kg) did not cause significant changes in level of sedation or alfaxalone-induction dose. During induction and recovery, the goats were calm following all treatments, including the control group. Cardiorespiratory and blood-gas parameters were maintained within clinically acceptable limits. The present study showed that midazolam, administered alone or combined with butorphanol, produces a degree of sedation that significantly reduces the dose of alfaxalone required for induction of general anaesthesia in goats, without causing any major adverse cardiorespiratory effects.

Objectives To compare the anaesthetic, analgesic and cardiorespiratory effects of intramuscular (IM) medetomidine and ketamine administered alone or combined with morphine or tramadol, for orchiectomy in cats.Study Design Randomised, blinded, prospective clinical study.Animals Thirty client-owned cats. oxygen tension (mean ± SD: 66 ± 2 mmHg) was low, and, surgery increased systolic arterial blood pressure (p<0.001), haemoglobin saturation (p<0.001), respiratory (p=0.003) and heart rates (p=0.002), and decreased end-tidal carbon dioxide (p=0.003). Pain scores did not differ significantly between groups. Von Frey responses decreased over time, changes over time varied by treatment (p<0.001), the MedK group returning to baseline values more rapidly than MedKM and MedKT. None of the cats required rescue analgesics. Materials and Methods Conclusion and Clinical RelevanceAll three protocols provide adequate anaesthesia and analgesia for orchiectomy in cats. However, rescue intervention to maintain surgical anaesthesia such as isoflurane may be required in some cats. Oxygen supplementation is advised.

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