MRI and articular cartilage

There are considerable laboratory data and information from animal and continuous culture in vitro models to support continuous infusion therapy for penicillins and cephalosporins, but, as yet, the only existing clinical data relate to cephalosporins. Penicillins do not exert concentration-dependent killing in the therapeutic range but have a post-antibiotic effect (PAE) against Gram-positive cocci but not Gram-negative rods. Animal models indicate the time (T) during which the serum concentrations exceed the minimum inhibitory concentration (MIC) of the pathogen [T > MIC] determines outcomes. Pharmacokinetic studies in humans indicate that continuous infusion with penicillins is possible but there are no clinical data on efficacy. Cephalosporins have similar pharmacodynamic properties to penicillins; T > MIC determines outcome. Data related to ceftazidime indicate that the drug concentration at steady-state (Css) should exceed the pathogen MIC by > 1-fold and perhaps by 4- to 5-fold or more. Human pharmacokinetics of ceftazidime administered by continuous infusion to a wide variety of patient groups indicates that Css of > 20 mg/L can easily be achieved using conventional daily doses. Clinical data indicate increased effectiveness of a continuous regimen in neutropenic patients with Gram-negative infection. Furthermore cefuroxime administration by continuous infusion has resulted in lower doses and shorter course durations. Little is known of the pharmacodynamics of monobactams and there are few clinical data on continuous infusion therapy. Carbapenems have different pharmacodynamics to other beta-lactams as they have concentration-dependent killing and a PAE with both Gram-positive and Gram-negative bacteria. While T > MIC has a role in determining outcomes, the proportion of the dosing interval for which serum drug concentrations should exceed the pathogen MIC is less than for other beta-lactams. In vitro models have shown that continuous infusion is effective, as is less frequent dosing. There are few data on continuous infusion of carbapenems but some patients have been treated with once-daily dosing. Clinically, continuous infusion therapy with penicillins and cephalosporins should be considered in patients infected with susceptible Gram-negative rods not responding to conventional therapy. As an approximation, the same total daily dose should be given but a bolus intravenous injection should be give at the start of continuous infusion to ensure Css is reached rapidly. The Css may be difficult to predict and determination of serum drug concentrations may be indicated. Ideally, the Css should be calculated based on the MIC of the potential pathogen and may be higher or lower than the Css achieved by a conventional daily dose.     

MR imaging of articular cartilage

Recent theoretical models suggest that males may respond to changes in paternity by adjusting their parental effort. Male response will depend on the availability of reliable paternity cues and the relative costs and benefits of parental effort to the male (i.e. its effect on the survival of young and alternative mating opportunities). Males breeding in pairs may be constrained because reductions in male parental effort are unlikely to be compensated for by the female and thus the survival of both related and unrelated young may decrease. In contrast, males breeding in cooperative groups (i.e. with helpers or co-breeders) may not have this constraint if other individuals in the group compensate for reductions in male parental effort. White-browed scrubwrens, Sericornis frontalis, breed in pairs and cooperative groups, typically with one female and two males (alpha and beta). We found that male parental effort was related positively to paternity for beta males, but not for alpha or pair males. Alpha males had paternity in all broods and always fed young. In contrast, beta males often had no paternity and sometimes did not feed young. Time spent near the fertile female was not an accurate predictor of the percentage of young sired in a brood, but it was a good predictor of having sired young in a brood. Our results are consistent with the idea that male parental effort is allocated according to whether or not the male copulated with the female. We suggest that the relationship between male parental effort and paternity may vary among cooperatively breeding species depending on the type and availability of cues to a male's paternity. Copyright 1998 The Association for the Study of Animal Behaviour Copyright 1998 The Association for the Study of Animal Behaviour.     

Human joint performance and the roughness of articular cartilage

The Doppler technique has been used to evaluate venous reflux in the spermatic cord. Valsalva-induced reflux occurred on the left side in 83% and on the right side in 59% of 118 patients without clinical varicoceles and there was no difference in incidence between fertile and infertile men. The significance of Valsalva-induced reflux should be questioned. Greater importance should be attributed to the spontaneous venous reflux that occurred during quiet respiration in the majority of patients with varicoceles. Seven velocity waveform patterns are described and these are thought to represent increasing degrees of internal spermatic vein reflux and provide a basis on which it is possible to grade varicoceles. The Doppler grades correlated with the size of the varicocele, and with the internal spermatic vein diameter and testosterone concentrations.     

The fate of the articular cartilage in intracapsular fracture of the femoral neck (articular cartilage in femoral neck fracture)

The fate of the articular cartilage of the hip joint with intracapsular neck fracture was studied by histological, histochemical and autoradiographic techniques and by using a polarized microscope and a scanning electron microscope. Cartilage specimens from 93 femoral heads and 7 acetabula were obtained from fractured hips 2 days to 4 1/3 years postfracture and from control hips with various disorders. The cartilage degeneration appeared 2 weeks after fracture and advanced steadily with time. The matrix was covered, invaded and ultimately replaced by the fibrous tissue. Chondrocyte viability, though it was lost from the surface, was recognized in the deep matrix even in the oldest fracture examined. It is concluded that the humoral factor directly caused by the injury as well as the biomechanical impairment, i.e. a loss of physical stress, may play an essential role in the pathogenesis of the degeneration. The possibility of regeneration was discussed.     

Chondromodulin-I expression in rat articular cartilage

The localization and expression of chondromodulin-I (ChM-I), an angiogenesis inhibitor, in the rat articular cartilage during maturation from 2 to 10 weeks of age were examined by immunohistochemistry, Western blot analysis and ribonuclease protection assay, and the results were compared with those in the epiphyseal cartilage. ChM-I was found to be diffusely immunostained in the inter-territorial space of the cartilage matrix from the intermediate to the deep layers at the immature stage. As the articular cartilage matured, the immunoreactivity was localized around the hypertrophic chondrocytes in the deep layer and the immunoreactivity became weak after maturation. In contrast, the ChM-I immunoreactivity was intense in the epiphyseal cartilage at all ages examined. ChM-I was detected by Western blotting as a broad band or occasionally as a cluster of multiple bands (approximately 25 kDa) in both the articular and the epiphyseal cartilage. The intensity of the bands decreased gradually with age in the articular cartilage, but was unchanged in the epiphyseal cartilage at all ages. Ribonuclease protection assay revealed that ChM-I mRNA also decreased gradually with age in the articular cartilage in parallel with the maturation of the articular cartilage, while no decrease in ChM-I mRNA was found in the epiphyseal cartilage. The expression of ChM-I mRNA in the articular cartilage was less than that in the epiphyseal cartilage at all ages. The decrease in amount of ChM-I in the mature articular cartilage suggests that ChM-I plays a more important role in the maintenance of avascularity in the immature articular cartilage than in the mature one. The avascular condition may be preserved by angiogenic inhibitors or mechanisms other than ChM-I in the mature articular cartilage.     

Ultrastructure of articular cartilage of achondroplastic mice

Articular chondrocytes of achondroplastic mice (cn/cn) resemble ultrastructurally those of their non-achondroplastic siblings (Cn/Cn or Cn/cn), except for premature deposition of glycogen and a tendency to undergo regression. The latter may be slight or extreme. The ultimate cause of the vulnerability of the chondrocytes and the cause of the heterogeneity of the reaction could not be determined with the method employed. Nevertheless, increased vulnerability accounts for cell death under conditions which are usually not injurious, and which may be either physiologic or altered by endogenous or exogenous factors.     

Membrane transport properties of bovine articular cartilage

The thermodynamic parameters which define transport of nonelectrolytes through bovine articular cartilage membranes were evaluated. H3HO, glucose and sucrose were used as permeants. These solutes permeate more readily through the upper layers (near the articular surface) than through the denser deeper layers approaching bone. Cartilage is similar in many respects to a swollen cellulose gel. Viscous-flow contributes importantly to transport within cartilage thus greatly enhancing the movement of nutrients.     

Reaction of hypochlorous acid with bovine nasal cartilage comparison to pig articular cartilage

The action of sodium hypochlorite (NaOCl) on bovine nasal cartilage was studied by proton nuclear magnetic resonance (1H-NMR) spectroscopy in order to model degradation processes of cartilage caused by neutrophil-derived hypochlorous acid. Nasal cartilage was chosen as a mean of comparison because it differs from articular cartilage in its composition. It contains some more proteoglycans, i.e. polymeric carbohydrates and less collagen than articular cartilage. This is important for studying the influence of hypochlorous acid on cartilage components (collagen and polysaccharides). Cartilage samples were incubated at 37 degrees C with phosphate buffer in the presence or absence of NaOCl. Supernatants were collected and assayed by NMR-spectroscopy. In the presence of pure phosphate buffer, the supernatants of bovine nasal cartilage were less rich in low molecular mass metabolites (e.g. amino acids, lactate) than articular cartilage. However, intense signals for highly mobile N acetyl groups of cartilage polysaccharides were detectable in nasal cartilage. NaOCl caused an increase in signals for acetate and formiate. Signals for N-acetyl groups rose only during the first 25 minutes of incubation with NaOCl. Then, their concentration decreased markedly. These changes were related to an enhanced release of chondroitinsulfate from nasal cartilage.     

Ultrastructural changes in articular cartilage in rheumatoid arthritis

Electron microscope studies of the articular cartilages removed in the course of the operation on 6 patients with rheumatoid arthritis were carried out. The processes of destruction of chondrocytes and the cartilaginous matrix in different regions of the articular cartilage were traced. In the surface areas of the drastically changed cartilage there were observed leucocytes of the synovial fluid, and in deeper areas--disintegration of chondrocytes and extracellular disposition of lysosomes and altered organellas, destroyed cartilaginous cells. In these areas destruction of collagenous fibres was particularly intensive. In areas of the tissue remote from the destuction hypertrophy of chondrocytes due to hyperplasia of various organellas and the Golgi complex in particular were noted. In the Golgi zone granules of glycogen were detected. No mitoses were observed. Apparently, the enzymatic destruction of the cartilaginous matrix in rheumatoid arthritis could proceed at the expense of the activazation of the synovial fluid lysosomes and lysosomes of chondrocytes themselves. A reparative regeneration of the disintegrating matrix was realized mainly because of hypertrophy of the functionally preserved chondrocytes.     

Variations in thickness of articular cartilage in the human sacroiliac joint

Differences in articular cartilage thickness in the sacroiliac joint were investigated in different regions of the sacral and the iliac articular surfaces in the embalmed cadavers of five males and six females. The mean thickness of the sacral articular cartilage was greater than that of the iliac articular cartilage (P < 0.001) and the sacral articular cartilage of the female was thicker than that of the male (P < 0.02). Differences between thicknesses of the iliac articular cartilage in the male and female and in different regions of the sacral and iliac articular cartilages were found to be not significant.     

Biomechanical topography of human articular cartilage in the first metatarsophalangeal joint

The objective of this study was to provide a map of cartilage biomechanical properties, thickness, and histomorphometric characteristics in the human, cadaveric first metatarsophangeal joint, to determine if normal articular cartilage was predisposed topographically to biomechanical mismatches in articulating surfaces. Cartilage intrinsic material properties and thickness were obtained from seven pairs of human, freshly frozen, cadaveric, metatarsophalangeal joints using an automated creep indentation apparatus under conditions of biphasic creep. Eight sites were tested: four on the metatarsal head, two on the proximal phalanx base, and one on each sesamoid bone to obtain the aggregate modulus, Poisson's ratio, permeability, shear modulus, and thickness. Cartilage in the lateral phalanx site of the left metatarsal head had the largest aggregate modulus (1.34 MPa), whereas the softest tissue was found in the right medial sesamoid (0.63 MPa). The medial phalanx region of the right joint was the most permeable (4.56 x 10(-15) meter4/Newton-second), whereas the medial sesamoid articulation of the metatarsal head of the left joint was the least permeable (1.26 x 10(-15) meter4/Newton-second). Material properties and thickness are indicative of the tissue's functional environment. The lack of mismatches in cartilage biomechanical properties of the articulating surfaces found in this study may be supportive of clinical observations that early degenerative changes, in the absence of traumatic events, do not occur at the selected test sites in the human first metatarsophalangeal joint.     

Increase of decorin content in articular cartilage following running

The effect of long distance running exercise (40 km/day for 15 weeks, five days a week) on the decorin content of articular cartilage from the knee joint was studied in female beagle dogs. Samples from load bearing sites on the lateral plateau of the tibia (TL), and pooled material from two minimum load bearing sites on the posterior section of lateral (FLP) and medial (FMP) femoral condyles were analyzed. The running exercise protocol did not lead to significant changes in the overall glycosaminoglycan content of the cartilage. However, the amount of decorin significantly increased in the TL samples, and also in the FMP pool. These results support earlier in vitro observations that decorin synthesis is stimulated by loading, independent of the synthesis of aggrecan.     

Low-selenium diet, bone, and articular cartilage in rats

The pathophysiology of secondary osteoarthritis remains largely obscure. Our attention has been drawn to Kashin-Beck disease (KBD), which has been attributed to Se deficiency. To obtain information regarding the prevention, prediction of progression, and treatment of this condition, we performed histological and biochemical studies on bone and articular cartilage specimens obtained from rats fed a low-Se diet. A low-Se diet was prepared and fed to Wistar rats for 3-11 mo, after which the rats were killed under general anesthesia, and their articular cartilages were studied microscopically and electron microscopically. The bone mineral density (BMD) of the femur was determined by the microdensitometry method and ash weight. In addition, serum Se, Ca, P, Alk Phos, T3, T4, and urinary Se were measured. In the low-Se group, impaired weight gain was observed from the 5th mo, and head alopecia was found in 60% of the animals. Microscopically, no clear changes in the articular chondrocytes were apparent, whereas with the electron microscope, chondrocytes in the deep layer showed degeneration of nuclei and endoplasmic reticular ballooning. From the 5th mo, a decrease in BMD (ash weight) was noted. Serum Se concentrations, alkaline phosphatase activity, and urine Se concentrations were decreased in the Se-deficient rats, whereas serum Ca, P, T3, and T4 values did not differ from those of a control group. Also, a decrease in sulfotransferase activity, which is involved in transfer in the process of synthesis of glycosaminoglycan, which is a proteoglycan carbohydrate chain, was found.(ABSTRACT TRUNCATED AT 250 WORDS)     

Fibronectin synthesis in superficial and deep layers of normal articular cartilage

OBJECTIVE: To study the distribution and synthesis of fibronectin (FN) in superficial and deep layers of normal articular cartilage. METHODS: Superficial and deep bovine and human articular cartilage slices were used to extract and quantitate FN by radioimmunoassay. Chondrocytes were also isolated by collagenase digestion for FN extraction and culture. Superficial and deep cartilage explants were cultured with and without stimulation by cytokines. Quantitation of newly synthesized FN was carried out by incubation with 35S-methionine. FN was purified on gelatin-agarose columns and further characterized by polyacrylamide gel electrophoresis. FN messenger RNA (mRNA) was quantitated by Northern blot analysis. RESULTS: Freshly isolated bovine chondrocytes from deep cartilage contained 2.3 +/- 0.2 times more FN than was found in superficial cells (P < 0.025). Deep cartilage explants contained 1.2 times more FN than was found in superficial tissue. Explants obtained from deep cartilage synthesized 2.4 times more FN per cell than did superficial tissues (P < 0.01). FN synthesis as a fraction of total protein synthesis was significantly greater in deep explants (P < 0.01) compared with superficial tissues. Isolated deep chondrocytes in culture synthesized 1.89 +/- 0.33-fold more FN than did superficial cells (P < 0.05). Cytokine-stimulated superficial cartilage explants failed to respond in terms of FN synthesis. FN mRNA quantitation showed no significant differences between superficial and deep populations. CONCLUSION: Since FN plays a major role in cell adhesion to damaged cartilage surfaces, our results suggest that modulation of FN synthesis near the articular surface of cartilage may be one of the factors that impede pannus invasion following an inflammatory insult to the joint.     

Treatment of articular cartilage defects of the knee with autologous chondrocyte implantation

alpha 1-Adrenergic receptor-mediated responses are overwhelming in adult rat hepatocytes. Inversely, beta-responses are predominant over alpha 1-responses in the hepatocytes that have been cultured at a low cell density (10(4) cells/cm2) for 24 h. The insulin-EGF-induced DNA synthesis in the beta-response-dominant hepatocytes was doubled by beta-agonists or cAMP-generating agents added far behind (16-20 h) the addition of insulin/EGF; i.e., immediately before the entry into the S-phase of the cell cycle. Agonists of alpha 1-adrenergic or other Ca2+, mobilising receptors added to the alpha 1-response-dominant hepatocytes increased DNA synthesis only if they were added within 1-2 h after the addition of insulin/EGF, at the early stage of G1-phase. Agonists of "non-dominant" receptors were rather antagonistic to agonists of "dominant" receptors. Thus, agonists of alpha 1-adrenergic (and other Ca2+ mobilising) receptors and agonists of beta-adrenergic (and other cAMP-generating) receptors acted as comitogens in their own particular manners in the presence of growth factors in hepatocytes in which the respective receptor functions were dominant.     

A theoretical formulation for boundary friction in articular cartilage

In this paper we report the cloning and characterization of cDNA encoding a novel, short form of heparin-binding EGF-like growth factor (SF HB-EGF), and show expression of specific mRNA in various tissues and cell types. Our data suggest that SF HB-EGF mRNA is a product of alternative splicing. Like normal HB-EGF, SF HB-EGF contains the signal peptide, the propeptide, the heparin-binding domain and the first two conservative disulfide loops of the EGF unit. Instead of the third disulfide loop, the spacer, the transmembrane and the cytoplasmic domains, SF HB-EGF has a nine amino acid tail.     

Rabbit articular cartilage defects treated with autologous cultured chondrocytes

Adult New Zealand rabbits were used to transplant autologously harvested and in vitro cultured chondrocytes into patellar chondral lesions that had been made previously and were 3 mm in diameter, extending down to the calcified zone. Healing of the defects was assessed by gross examination, light microscope, and histological-histochemical scoring at 8, 12, and 52 weeks. Chondrocyte transplantation significantly increased the amount of newly formed repair tissue compared to the found in control knees in which the lesion was solely covered by a periosteal flap. In another experiment, carbon fiber pads seeded with chondrocytes were used as scaffolds, and repair significantly increased at both 12 and 52 weeks compared to knees in which scaffolds without chondrocytes were implanted. The histologic quality scores of the repair tissue were significantly better in all knees in which defects were treated with chondrocytes compared to knees treated with periosteum alone and better at 52 weeks compared to knees in which defects were treated with carbon scaffolds seeded with chondrocytes. The repair tissue, however, tended to incomplete the bonding to adjacent cartilage. This study shows that isolated autologous articular chondrocytes that have been expanded for 2 weeks in vitro can stimulate the healing phase of chondral lesions. A gradual maturation of the hyalinelike repair with a more pronounced columnarization was noted as late as 1 year after surgery.     

A novel cartilage protein (CILP) present in the mid-zone of human articular cartilage increases with age

A novel, somewhat basic noncollagenous protein was purified from guanidine hydrochloride extracts of human articular cartilage using cesium chloride density gradient centrifugation, followed by ion-exchange chromatography at pH 5, and gel filtration on two serially coupled columns of Superose 6 and Superdex 200. The protein of 91.5 kDa contains a single polypeptide chain substituted with N-linked oligosaccharides. It appeared unique to cartilage as studied by enzyme-linked immunosorbent assay and immunoblots of various tissue extracts. Its concentration in articular cartilages showed some variability with age being lower in young individuals. It represents a chondrocyte product, since it is synthesized by articular chondrocytes in explant cultures. Interestingly, the distribution of the protein in the articular cartilage provides important information on the nature of chondrocytes at different compartments in the tissue. Thus, chondrocytes in the middle/deeper layers of the tissue in particular, appeared to have produced the protein and deposited it in the interterritorial matrix. The protein was neither seen in the superficial nor in the deepest regions of the articular cartilage. Based on its immunolocalization we have named this protein CILP (cartilage intermediate layer protein).