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Background and Purpose: (R)-Ketamine (arketamine) may have utility as a rapidly acting antidepressant. While (R)-ketamine has lower potency than (R,S)-ketamine to inhibit NMDA receptors in vitro, the extent to which (R)-ketamine shares the NMDA receptor-mediated adverse effects of (R,S)-ketamine in vivo has not been fully characterised. Furthermore, (R)-ketamine is metabolised to (2R,6R)-hydroxynorketamine (HNK), which may contribute to its antidepressant-relevant actions.Experimental Approach: Using mice, we compared (R)-ketamine with a deuterated form of the drug (6,6-dideutero-(R)-ketamine, (R)-d2 -ketamine), which hinders its metabolism to (2R,6R)-HNK, in behavioural tests predicting antidepressant responses. We also examined the actions of intracerebroventricularly infused (2R,6R)-HNK. Further, we quantified putative NMDA receptor inhibition-mediated adverse effects of (R)-ketamine.Key Results: (R)-d2 -Ketamine was identical to (R)-ketamine in binding to and functionally inhibiting NMDA receptors but hindered (R)-ketamine's metabolism to (2R,6R)-HNK. (R)-Ketamine exerted greater potency than (R)-d2 -ketamine in several antidepressant-sensitive behavioural measures, consistent with a role of (2R,6R)-HNK in the actions of (R)-ketamine. There were dose-dependent sustained antidepressant-relevant actions of (2R,6R)-HNK following intracerebroventricular administration. (R)-Ketamine exerted NMDA receptor inhibition-mediated behaviours similar to (R,S)-ketamine, including locomotor stimulation, conditioned-place preference, prepulse inhibition deficits, and motor incoordination, with approximately half the potency of the racemic drug.Conclusions and Implications: Metabolism of (R)-ketamine to (2R,6R)-HNK increases the potency of (R)-ketamine to exert antidepressant-relevant actions in mice. Adverse effects of (R)-ketamine require higher doses than those necessary for antidepressant-sensitive behavioural changes in mice. However, our data revealing that (R)-ketamine's adverse effects are elicited at sub-anaesthetic doses indicate a potential risk for sensory dissociation and abuse liability. [ABSTRACT FROM AUTHOR]

Transabdominal ultrasound was used to monitor the reproductive tract of a female giant panda ( Ailuropoda melanoleuca) for three consecutive breeding seasons starting in 2001. Parturition did not occur in 2001 or 2002. In 2003, uterine enlargement was noted 109 days after natural mating occurred. A twin pregnancy was detected via transabdominal ultrasound 134 days following natural mating. Four subsequent ultrasound examinations, performed at 137, 138, 140, and 142 days postmating, documented fetal development. The female gave birth to one infant 150 days postmating. Zoo Biol 23:449-461, 2004. © 2004 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

IN TISSUES THAT CLOSELY APPROXIMATE bone, sufficient heat may he transferred to the bone during laser surgery to cause damage and/or necrosis. To date, there have been few studies examining the temperatures elicited at the bone surface as a result of laser application to the overlying soft tissues. The purpose of this investigation was to determine, under in vitro conditions, temperature changes at the bone/soft tissue interface during laser ablation with CO2 and Nd:YAG lasers used with and without (w/wo) air/water coolant. Experimental specimens consisted of 5 mandibles from freshly sacrificed hogs; laser treatment sites were the buccal and lingual attached gingival of the molars and the lingual keratinized mucosa of the incisor region. CO2 and Nd:YAG lasers were used two coolant at power settings of 4 to 8 W and 5 to 9 W, Respectively. Temperature changes were measured with a copper constant thermocouple contained within a 21 gauge hypodermic needle. In comparing the lasers at comparable energy densities w/wo coolant, temperature increases at the bone/soft tissue interface ranged from 8.0 to 11.1°C with the Nd:YAG and 1.4 to 2.1°C with the CO2. Similarly, in comparing the times required for the interface to return to baseline temperature following removal of the laser, values ranged from ~143 to 205 and ~119 to 139 seconds for the Nd:YAG and CO2, respectively. Results from this study suggest that, at energy densities equal or above those reported here, the increase in temperature at the bone surface as a result of periodontal soft tissue surgery with the Nd:YAG laser could be damaging, especially if the exposure is prolonged. [ABSTRACT FROM AUTHOR]