Osteoarthritis in cynomolgus macaques. III: Effects of age, gender, and subchondral bone thickness on the severity of disease.

Knee joints from cynomolgus monkeys of both genders and a wide range of ages were examined to characterize further the natural history of osteoarthritis (OA) in these animals. The objectives of this study were to characterize better the subchondral bone changes previously noted in this disease, to determine whether the severity of OA in these animals is affected by age or weight, and to determine whether males and females are affected similarly. As had been seen in previous studies, the medial tibial plateau was the most severely affected site. The thickness of the subchondral plate in the medial tibial plateau increased with increasing severity of articular cartilage lesions in both males and females; however, in monkeys with subchondral plate thicknesses less than 400 microns, articular cartilage lesions were essentially absent. Subchondral plate thickness increased with increasing weight in both genders, but females had a higher subchondral plate thickness than males for a given body weight. There was no correlation between bone volume in the proximal tibial epiphysis and articular cartilage lesions of OA. The prevalence and severity of OA in the medial tibial plateau increased with increasing age, but were not affected by gender or weight. Although there was no correlation between articular cartilage lesions and body mass index or weight, the waist/hip circumference ratio and severity of articular cartilage lesions were correlated in the female monkeys. This work provides evidence that thickening of the subchondral bone plate may be more important than the volume of epiphyseal/metaphyseal cancellous bone in determining the biomechanical stresses in the joint and in influencing the development of articular cartilage lesions.

Detection of intra-amniotic infection by gas-liquid chromatography.

The use of gas-liquid chromatography to detect short-chain organic acids in the amniotic fluid of patients with amnionitis has been previously described. Most of the studies describe patients in the early third trimester with such infections. The purpose of the current study was to confirm the correlation of infection with increased production of organic acids and to assess the effect of gestational age on the presence of these short-chain fatty acids in the amniotic fluid. Six patients with confirmed chorioamnionitis were used as positive control subjects. Seventy-two patients at various gestational ages from 18 to 42 weeks with negative Gram's stain and culture results from the amniotic fluid were used as negative control subjects. The data revealed an increased production of organic acids, particularly pyruvic, oxalic and succinic, in patients with amnionitis regardless of gestational age. Interestingly, patients with noninfected amniotic fluid also revealed an increase in the concentrations of volatile organic acids between 27 and 32 weeks' gestation. It appears from this study that previous results correlating chorioamnionitis with an increased production of organic acids in the amniotic fluid may have been confounded by gestational age.

Behavioral and neurochemical effects of continuous infusion of cocaine in rats.

The ability of continuous intravenous infusion of cocaine (60 mg/kg per day for 11 or 12 days; by osmotic minipump) to alter responses to acute injection of cocaine (20 mg/kg, i.p.; given 24 hr after termination of the infusion by minipump) was tested in conscious, tethered Sprague-Dawley rats. Extracellular levels of cocaine, dopamine and metabolites of dopamine in the striatum were determined by in vivo microdialysis. Locomotor activity and stereotyped behavior were evaluated simultaneously during dialysis sampling. Prior infusion of cocaine blunted the ability of acute challenge with cocaine to increase the efflux of dopamine in the striatum, locomotor activity and stereotypy. Increases in extracellular levels of homovanillic acid in the striatum were significantly greater in cocaine-infused rats than vehicle-infused controls, both prior to and after acute injections of cocaine. However, no differences between these two groups were observed in levels of cocaine in the striatum after acute challenge. Extracellular levels of dopamine in the striatum correlated significantly (P less than 0.05) with stereotypy in both groups but with locomotor activity only in cocaine-infused rats. The results indicate that behavioral tolerance occurred after continuous intravenous infusions of cocaine, that this was correlated with neurochemical tolerance to acute cocaine challenge and that alterations in the metabolism of cocaine did not account for the observed behavioral responses.

Cocaine elevates striatal dopamine efflux in spontaneously hypertensive and Wistar-Kyoto rats.

The effects of acute cocaine administration on central dopaminergic systems were examined in the striata of spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats with the use of an in vivo microdialysis technique. Increased extracellular levels of dopamine were observed for 45 to 75 minutes following acute cocaine administration in both halothane-anesthetized and conscious SHR and WKY. However, no significant differences were noted between anesthetized and conscious SHR and WKY in either baseline levels or cocaine-induced changes in extracellular levels of dopamine and its metabolites. A positive, linear correlation between extracellular levels of dopamine and cocaine was demonstrated for the 60-min period following acute cocaine administration in both SHR and WKY. The slopes of the linear regression plots obtained from the data of each 15-min sample was slightly, but significantly, higher in conscious SHR than in conscious WKY. The present results suggest a transient and dose-related stimulation of striatal dopamine release following acute cocaine administration and a linear relationship between striatal extracellular levels of dopamine and cocaine in both SHR and WKY.

The effect of activity state upon the production of lethalities due to the inhalation of the toxic pyrolysis products of polyacrylonitrile.

Hydrogen cyanide is known to be produced upon the pyrolysis of the synthetic material polyacrylonitrile. Cyanide inhibits phosphorylation reactions, therefore, decreasing the amount of high energy bonds available for metabolic use. Since the energy requirements, as well as the respiratory minute volume, for an individual decrease with decreasing activity, it was of interest to investigate whether diminished physical activity would decrease the lethal potential of the pyrolysis products of polyacrylonitrile. In order to produce wide variations in physical activity, male ICR mice were pretreated with either 8.6 mg/kg dextroamphetamine sulfate ip 30 min prior to challenge, 75 mg/kg sodium pentobarbital ip 15 min prior to challenge, or 10 ml/kg of 70 proof ethyl alcohol ip 15 min prior to challenge. Control animals received injections of 10 ml/kg normal saline ip 15 min prior to challenge. Animals were subsequently challenged with the cooled/filtered smoke from the pyrolysis of polyacrylonitrile fibers at 660 C. Increased physical activity decreased the exposure time necessary to produce death. Animals pretreated with amphetamine appear to die more rapidly than control animals due to an increase in respiratory minute volume. Animals pretreated with sodium pentobarbital or ethanol appear to survive through long periods of exposure to the toxic gases due to both a decrease in minute volume and a decrease in energy utilization.

New rapid method of analysis of cefoxitin in serum and bone, by high-performance liquid chromatography.

A method for the extraction and quantification of cefoxitin in blood and bone samples is described in this paper. The procedure, which prepares biological material for reversed-phase high-performance liquid chromatographic analysis is convenient, rapid and reproducible. It also allows for use of cephalothin as an internal standard in measuring serum cefoxitin levels. Conventional extraction procedures, involving use of organic solvents, generally yield drug recoveries of 60-80%. Use of Baker--10 SPE disposable extraction columns allowed us to consistently obtain greater than 98% recovery of both cefoxitin and cephalothin. Methods for quantification of the extracted drugs include comparison of peak ratios (for serum) or peak heights (for bone) to first-order equations obtained from regression analyses.

Effect of long-term continuous infusion of alfathesin on clinical biochemical and haematological parameters.

Clinical biochemical and haematological parameters during long-term continuous infusion of alfathesin were studied in twelve neurosurgical patients who did not have multiple organ failure. Significant changes which were possibly caused by alfathesin were an alteration of blood film morphology, an elevation of plasma triglyceride and a reduction in plasma high-density lipids.