Knee Posture Predicted from Subchondral Apparent Density in the Distal Femur: An Experimental Validation

Spatial patterning in the apparent density of subchondral bone can be used to discriminate between species that differ in their joint loading conditions. This study provides an experimental test of two hypotheses that relate aspects of subchondral apparent density patterns to joint loading conditions. First, the region of maximum subchondral apparent density (RMD) will correspond to differences in joint posture at the time of peak locomotor loads; and second, differences in maximum density between individuals will correspond to differences in exercise level. These hypotheses were tested using three age‐matched samples of juvenile sheep. Two groups of five sheep were exercised, at moderate walking speeds, twice daily for 45 days on a treadmill with either a 0% or 15% grade. The remaining sheep were not exercised. Sheep walking on the inclined treadmill used more flexed knee postures than those in the level walking group at the time of peak vertical ground reaction forces. Kinematic measurements of knee posture were compared with knee postures estimated from the spatial position of the RMD on the medial femoral condyle. Our results show that the difference in the position of the RMD between the incline and level walking groups corresponded to the difference in knee postures obtained kinematically; however, exercised and nonexercised sheep did not differ in the magnitude of apparent density. These results suggest that patterns of subchondral apparent density are good indicators of the experimental modifications in joint posture during locomotion and may, therefore, be used to investigate differences between species in habitual joint loading. Anat Rec, 291:293–302, 2008. © 2008 Wiley‐Liss, Inc.     

Lack of interaction between lomefloxacin and caffeine in normal volunteers.

Sixteen healthy, nonsmoking adult males participated in a randomized, double-blind, placebo-controlled, two-way crossover study to evaluate the influence of chronic lomefloxacin administration on the disposition of caffeine and its major metabolite, paraxanthine, at steady-state conditions. Lomefloxacin (400 mg) or placebo was administered orally once daily for 5 days to xanthine-free volunteers after an overnight fast. Caffeine (200 mg orally) was administered simultaneously with lomefloxacin on days 3 through 5. After a 2-day washout period, subjects were crossed over to the alternate 5-day regimen with caffeine, which was again given on the final 3 days. Blood samples for caffeine, paraxanthine, and lomefloxacin concentration determinations were serially collected for 48 h following the last dose of each regimen. All compounds were analyzed by high-performance liquid chromatography. For the placebo versus lomefloxacin-containing treatments, maximum caffeine concentrations in plasma (4.35 +/- 0.63 versus 4.07 +/- 0.56 micrograms/ml), areas under the concentration-time curve from time zero to 24 h at steady state (30.3 +/- 6.9 versus 29.7 +/- 6.6 micrograms.h/ml), and elimination half-lives of caffeine (4.8 +/- 1.1 versus 4.8 +/- 1.2 h) were not significantly different. In addition, there were no significant changes in the disposition parameters of paraxanthine as a result of lomefloxacin administration. The frequencies of central nervous system-related effects for the two treatments were not statistically different. We conclude that lomefloxacin has no significant effect on the disposition of caffeine in young healthy volunteers.     

Antibodies against arylcyclohexylamines and their similarities in binding specificity with the phencyclidine receptor

Rabbit antibodies were generated against five unique epitopes of phencyclidine (PCP)-like molecules to determine the molecular requirements for arylcyclohexylamine binding to the PCP receptor. Three of the haptens contained the three ring structures of PCP. A fourth hapten was synthesized from a derivative of the highly potent PCP analog, 1-[1-(2-thienyl)cyclohexyl]piperidine. The fifth hapten, 5-[N-(1'-phenylcyclohexyl)amino]pentanoic acid, was used as a haptenic model for N-ethyl-1-phenylcyclohexylamine, one of the most potent arylcyclohexylamines. These haptens were bound covalently to bovine serum albumin and were then used as antigens to immunize rabbits. The affinities and cross-reactivity patterns of the resulting five antibodies were studied in a [3H]PCP radioimmunoassay using standard curves of various arylcyclohexylamines. The dissociation constants ranged from 1.9 to 51.6 nM. From the average IC50 values of the radioimmunoassay dose-response curves, the relative potency of each ligand to PCP was determined. Least-squares linear regression was used to correlate these data with relative potency data from two [3H]PCP receptor binding assays and a PCP drug discrimination assay in the rat. Only relative potency data from the anti-5[N-(1'-phenylcyclohexyl)amino]pentanoic acid antibody showed a significant correlation with data from the three pharmacological studies (r2 = 0.80, 0.57 and 0.78, respectively; p less than .05 in all cases). These data indicated the 5-[N-(1'-phenylcyclohexyl)amino]pentanoic acid hapten contained the pharmacologically active features needed for arylcyclohexylamine binding to the PCP receptor.     

Renal clearance of canrenoate in normal man.

Potassium canrenoate was administered intravenously, twice at a 9-hr interval, to 3 apparently healthy male volunteers. No consistent changes in endogenous creatinine or PAH clearances were observed for 6 hr after the initial 200-mg dose of this aldosterone antagonist. The clearance of canrenone (the major gamma-lactone metabolite) exceeded by 70% the simultaneous clearance of creatinine from the second through the sixth hour. The excretion of canrenone amounted to 6.8 mg (3.4%) of the dose during the 6-hr clearance study, but was nearly absent (0.2 mg) during the ensuing 6- to 9-hr period. The cumulative excretion of the glucuronide conjugate of canrenone amounted to 4.6 and 2.8 mg (2.3% and 1.4%) of the dose during these respective periods. A sustained retention of K was observed in 1 subject. Otherwise, as was anticipated in the absence of hyperaldosteronism, urinary electrolyte levels were essentially unchanged. Circulating aldosterone and plasma renin activity levels were essentially unaltered.     

Adaptive differentiation of murine lymphocytes. IV. (Responder × Nonresponder) F(1) T cells can be taught to preferentially help nonresponder,rather than responder, B cells

Responses to the synthetic terpolymer L-glutamic acid, L-lysine, L-tyrosine (GLT) in the mouse are controlled by H-2-1inked Ir-GLTgenes. (Responder × nonresponder) F(1) hybrid mice, themselves phenotypic responders, can be primed with GLT to develop specific helper cells capable of interacting with 2,4-dinitrophenyl hapten (DNP)-primed F(1) B cells in response to DNP-GLT. Unlike the indiscriminant ability of F(1) helper T cells for conventional antigens (i.e. not Ir gene-controlled), which can help B cells of either parental type (as well as F(1)) equally well, GLT-primed F(1) T cells can only provide help under normal circumstances for B lymphocytes of responder parent origin; they are unable to communicate effectively with nonresponder parental B cells (1, and the present studies). The present studies reveal, however, that the induction of a parental cell-induced allogeneic effect during priming of F(1) mice to GLT actually dictates the direction of cooperating preference that will be displayed by such F(1) helper cells for B cells of one parental type or the other. Thus, F(1) T cells, primed to GLT under the influence of an allogeneic effect induced by parental BALB/c cells, develop into effective helpers for nonresponder A/J B cells, but fail to develop effective helpers for responder BALB/c B cells, and vice-versa. In contrast, F(1) T cells, primed to GLT under the influence of an allogeneic effect induced by either parental type, display significantly enhanced levels of helper activity for B cells derived from F(1) donors. These results are interpreted to reflect the existence of two interdependent events provoked by the allogeneic effect: one event augments the differentiation of GLT-specific helper T cells belonging to the subset corresponding to the opposite parental type; this would explain the development of increased helper activity provided to partner B cells of opposite parental type (as well as of F(1) origin). The second event, we postulate, involves the production of responses against the receptors which normally self-recognize native cell interaction determinants; this form of anti-idiotype response is restricted against self- recognizing receptors of the same parental type used for induction of the allogeneic effect, hence explaining diminished helper activity of such F(1) cells for partner B lymphocytes of corresponding parental type.