D. C. Van Sickle

Measurement of the total motion between two body segments — II Description of application☆

The total motion between two body segments can be measured accurately if all six possible degrees of freedom between the two body segments are considered. Part I of this paper (Kinzel et al. 1972) described the analytical basis for a measurement scheme capable of considering all six degrees of freedom. The objective of part II is to describe an application of the measurement system to a study of the motion in the shoulder joint of a dog. The design of the instrumented spatial linkage used to make the measurements and the use of the linkage data to determine both the gross relative motion of the scapula with respect to the humerus and the detailed relative motion between the two articulating surfaces of the shoulder joint are described.

Chondrotoxicity of ciprofloxacin in immature beagle dogs: immunohistochemistry, electron microscopy and drug plasma concentrations.

Abstract The systemic effects of ciprofloxacin in immature Beagles were studied. Dogs of 10–11 weeks were dosed orally for 5 days with 0 (n=3), 30 (n=5) and 200 (n=5) mg ciprofloxacin/kg body wt. Plasma concentrations were measured by high-performance liquid chromatography (HPLC) 1 h after dosing (assuming to be peak concentrations). In view of the high doses used, the plasma concentrations were rather low and declined during the study period. For example, plasma concentrations in the high dose group were 6.6 ± 0.9 mg/l (day 1), 3.9 ± 1.4 mg/l (day 3), and 2.6 ± 1.6 mg/l (day 5). In control dogs and in dogs treated with the low dose of ciprofloxacin no pathological changes were seen by light microscopy. However, cleft formation and erosions were observed in joint cartilage from two of five dogs treated with 200 mg/kg. It is noteworthy that despite the high dose used cartilage lesions were not detectable in all five dogs of this group by light microscopy. Using antibodies against cell membrane receptors (e.g. the α5β1-integrin) or matrix components (fibronectin, collagen II) the articular cartilage effects were studied in detail by immunohistochemistry. The most sensitive alteration was an increase in fibronectin which was detectable in the vicinity of the lesions in cartilage samples from the group of dogs administered the high dose. No clear-cut changes were seen with the use of antibodies against other matrix components. Electron microscopy revealed typical alterations in chondrocytes from dogs treated with ciprofloxacin: e.g., swollen mitochondria and enlarged rough endoplasmic reticulum. These changes were much more pronounced in dogs from the high dose group than in dogs from the low dose group. Our main conclusion is that after oral administration ciprofloxacin exhibits rather low chondrotoxicity, even in the most sensitive species known to date. This correlates with the findings in humans that ciprofloxacin seems to be less chondrotoxic than pefloxacin or other quinolones.

Fetal effects of cadmium in pregnant rats on normal and zinc deficient diets

SummaryThis investigation has shown that not only the extent of fetal resorption and malformation but also the types of malformation seen in rats depend upon the strain used and day of gestation. Furthermore, the effects of zinc deficiency and cadmium administration on the fetus can be at least additive, as was seen for malformations. For fetal resorption, zinc deficiency potentiated the action of cadmium.

Histochemical evidence of a functional heterogeneity in neonatal canine epiphyseal chondrocytes.

SynopsisThe chondrocytes of the neonatal proximal humeral chondroepiphyses of twelve purebred English pointer pups were investigated histochemically, using frozen serial sections, for chondroitin sulphate and for the following enzyme activities: lactate dehydrogenase, NAD and NADP transhydrogenases, glutamate dehydrogenase, isocitrate dehydrogenase, malate dehydrogenase, glucose-6-phosphate dehydrogenase, ATPase, succinate dehydrogenase, and UDPgalactose 4-epimerase. By using Alcian Blue with and without a prior digestion in testicular hyaluronidase, and Alcian Blue in the presence of 0.9 M magnesium chloride, it was found that about half the chondrocytes stained as if they were producing significant amounts of chondroitin sulphate. Only one enzyme, UDPgalactose 4-epimerase (which is involved in the biosynthesis of chondroitin sulphate), was found to have a similar staining heterogeneity. Therefore, it was concluded that the chondrocytes studied possessed a functional heterogenicity with particular reference to chondroitin sulphate synthesis while appearing morphologically homogeneous.

Histochemical evidence of a functional heterogeneity of the chondrocytes of adult canine articular cartilage

SynopsisTwenty humeral heads were collected from 10 adult English Pointer dogs, fixed in 15% formalin containing cetylpyridinium chloride, decalcified, processed for paraffin sections, and cut serially. The articular cartilage was studied by staining principally with Alcian Blue in the presence of 0.4 or 0.9m MgCl2 with and without a van Gieson counterstain. The results of the differential staining procedures demonstrated the existence of two groups of chondrocytes with distinctly different staining affinities. One group reacted intensely for the presence of protein-polysaccharides within its cytoplasm while the other group completely lacked this property. An approximate proportionality of 3∶1 of the protein polysaccharide-positive and-negative chondrocytes was observed in the tangential layer and upper intermediate zone. In the lower intermediate zone, radiate zone, and zone of calcified cartilage, the chondrocyte types were present in equal proportions. Staining with Alcian Blue in the presence of 0.9m MgCl2 with and without a van Gieson counterstain indicated a further subdivision of the protein-polysaccharide positive group of chondrocytes. This blocking technique has been reported to distinguish between chondroitin sulphate and high mol. wt. keratosulphate. Thus, based upon a greatly decreased number of the blue-stained chondrocytes after staining with Alcian Blue in the presence of 0.9m MgCl2 the hypothesis is put forward that some chondrocytes produce primarily chondroitin suphate and others produce both chondroitin sulphate and keratosulphate.

Improved osseointeraction of calcium phosphate-coated external fixation pins Studies in calves

We investigated osseointeraction of solution-precipitated calcium phosphate (SPCP)-coated transfixation pins used in external skeletal fixation of a calf stable fracture model. One group (SPCP) received centrally-threaded transfixation pins which had SPCP coating; the other group (control) received identical, but not coated, pins. Radiographs were obtained 1 and 40 days after surgery and examined for evidence of osteolysis. Bone phase 99mTc-MDP studies were performed 6 and 28 days after surgery. Calves were killed 40 days after surgery and mechanical tests performed. Dual-energy x-ray absorptiometry (DEXA) and histomorphometric analyses were done. A smaller proportion of SPCP pins (5/24) had evidence of discharge during the study compared with control pins (21/24). A smaller proportion of SPCP pins (4%) had radiographic evidence of osteolysis compared with control pins (42%). Uptake of 99mTc-MDP was similar for SPCP and control calves. Uptake was significantly greater in bone segments showing radiographic evidence of osteolysis than in bone segments not having osteolysis. Yield stress (MPa) for axial displacement was similar in the treatment groups. Bone mineral density was less in SPCP pins. Affinity index and interface histologic score were greater and osteoclastic index less in SPCP calves. Coating of transfixation pins with solution-precipitated calcium phosphate improved the osseointeraction of pin and bone during this 40-day study.

Prostaglandins in inflammatory bone pathology: mechanism and therapeutic benefit of etodolac.

To investigate the role of PGE2 in the development of bone and joint pathology in rat adjuvant arthritis, hindlimb paws were evaluated by calcified tissue histologic techniques focusing on histochemical visualization of cartilage and bone lesions. Case studies of hindlimbs from normal, adjuvant arthritic, and etodolac-treated arthritic rats demonstrated the association of disease severity with inflammation, chondromalacia, replacement of adipose bone marrow with a fibroid marrow, osteoclastic bone resorption, synovial cysts, and pannus formation within the joints. Extensive periosteal intramembranous bone formation was temporally associated with joint destruction and medullary tissue pathology.In vivo data were correlated within vitro effects of inflammatory mediators (IL-1, PGE2) on bone resorption. Etodolac blocked bone explant PGE2 accumulation at concentrations of 10−7M and higher, and inhibited bone resorption at concentrations of 10−5M and higher. The data indicate thatin vitro andin vivo models of bone metabolism are well correlated regarding prostaglandin synthesis; that the inflammatory mediator PGE2 is largely responsible for the involvement of skeletal tissue in the adjuvant arthritis model; and that the effects of etodolac are specifically mediated by its ability to inhibit PGE2 accumulationin vivo.

The biodistribution of [75Se]bis[β-(N,N,N-trimethylamino)ethyl]selenide diiodide in adult guinea pigs

The biodistribution of [75Se]BISTAES was studied in guinea pigs. A higher concentration of radioactivity was observed in articular cartilage than in other tissues or organs. A minimal amount of radioactivity was found in the blood, muscle and bone. The compound was excreted rapidly in urine. The target to background ratios were encouraging. [75Se]BISTAES has potential as an articular cartilage imaging agent and further studies in osteoarthritic animals are merited.

Chondrotoxicity of Ciprofloxacin in Immature Beagle Dogs

Quinolone-induced arthropathy was first described more than 2 decades ago in immature dogs.[1,2] However, the issue of quinolone-induced arthropathy is still discussed controversially with respect to its relevance to man. The vast majority of data on quinolone use in children and adolescents have derived from the use of ciprofloxacin in patients with cystic fibrosis.[3,4] Obviously, ciprofloxacin is rather well tolerated in juveniles, which is in contrast to the experience with other drugs of this group such as pefloxacin.[5,6] Since ciprofloxacin was not considered for treatment of juvenile patients when it was marketed in 1986, no detailed studies on the chondrotoxic effects of this compound have been published. Only summary data of the experiments performed by the manufacturer are available.[7] Because of the lack of data from studies in dogs with the most widely used quinolone, we decided to study the effects of ciprofloxacin in juvenile beagles by light and electron microscopy and to measure plasma drug concentrations during a 5-day treatment period.

Evaluation of Chromatin Clumping and Myelination of the Spinal Cord of Pigs with Congenital Tremor

Clumps of chromatin in the spinal cord of 2- to 10-day-old pigs with congenital tremor were of no diagnostic value since they were present also in unaffected pigs of the same age. No differences in shape, size, number, location, and staining characteristics of the clumps were found. The clumps were thought to be evidence of cellular necrobiosis. The cords of pigs with tremor had distinctly less myelin than those of normal pigs.