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Social short-term memory in rodents is based on the recognition of a juvenile by an adult conspecific when the juvenile is presented on two successive occasions. Cannabimimetics are claimed to induce memory deficits in both humans and animals. In the brain, they mainly bind to CB1 receptors for which anandamide is a purported endogenous ligand. SR 141716, a specific antagonist of CB1 receptors, dose-dependently reverses biochemical and pharmacological effects of cannabimimetics. More particularly, it antagonizes the inhibition of hippocampal long-term potentiation induced by WIN 55,212-2 and anandamide, and it increases arousal when given alone. The present experiments study the ability of SR 141716 (from 0.03 to 3 mg/kg SC) to facilitate short-term olfactory memory in the social recognition test in rodents. SR 141716 improved social recognition in a long intertrial paradigm with a threshold dose of 0.1 mg/kg SC. At 1 mg/kg, it antagonized the memory disturbance elicited by retroactive inhibition. Scopolamine (0.06 mg/kg IP) partially reversed its memory-enhancing effect. Moreover, SR 141716 reduced memory deficit in aged rats (0.03–0.1 mg/kg) and mice (0.3–1 mg/kg). As SR 141716 is not known to exhibit any pharmacological activity which is not mediated by CB1 receptors, the results strongly support the concept that blockade of CB1 receptors plays an important role in consolidation of short-term memory in rodents and suggest there may be a role for an endogenous cannabinoid agonist tone (anandaminergic) in forgetting.

Laboratory rearing of Phormia regina Meigen larvae on pork and venison was conducted as part of a study to determine whether forensic entomology approaches can be used in wildlife poaching investigations. Larvae were reared at 30°C, 75% relative humidity, and a photoperiod of 14:10 (L:D) h on pork or venison diets, and samples were collected every 8 h until >90% of the maggots reached the third-instar wandering or prepupal stage. Significant differences were found in the distribution of lengths of the third instar and combined instars for maggots reared on the two different meat sources. Maggots reared on venison reached the prepupal wandering stage significantly faster (≈6 h) compared with maggots on the pork diet. Mean adult weight and wing length of venison-reared flies were significantly greater than for flies reared on pork. The lower crude fat content of venison appears to make this meat source a more suitable medium than pork for larvae of P. regina. The difference in growth rate could introduce error into PMImin estimations from third-instar maggots in deer poaching cases if estimates are based on data from studies in which maggots were reared on pork.

Introduction: Rituximab (R) is an integral component of therapy for B-cell lymphoid malignancies; bortezomib (Btz) has shown provocative single agent activity in Follicular Lymphoma (FL), Mantle Cell Lymphoma (MCL) and Waldenström’s Macroglobulinaemia (WM), providing the rationale for investigating the combination. Patients+Methods: Forty-five adult patients (pts.) (30 men, 15 women) with histologically confirmed recurrent CD20+ve FL, MCL or WM, median age 60 years (range 45-79), FL: 17, MCL: 18, WM: 10, stage III/IV 40 (93%), bone marrow (BM) infiltration 32 (73%), elevated LDH 22 (49%), performance status ≥1 22 (49%), were enrolled in a randomised trial comparing 2 schedules of Brz+R: Arm A (twice weekly) Btz: 1.3mg/m2 (on days 1, 4, 8, 11 of a 21-day cycle) and R: 375mg/m2 (on day 1) for 8 cycles, or Arm B (weekly) Btz: 1.6mg/m2 (on days 1, 8, 15, 22 of a 35-day cycle) and R: 375mg/m2 (on days 1, 8, 15, 22 of cycles 1 and 4) for 6 cycles (23 arm A, 22 arm B). The median number of previous treatments was 2 (range 1-7). Seventeen pts. had received a R-containing regimen, with response lasting >6 months, and 8 high-dose treatment. Response was evaluated using the IWR criteria (Cheson et al, JCO17: 1244, 1999) and the updated response criteria from the 3rd International Workshop on WM (Treon et al, Blood107: 3442, 2006) Results: Ability to deliver the therapy, toxicity and efficacy were equivalent in both arms. The median number of cycles given in arm A was 4 and 5 in arm B. Haematological toxicity (grade≥3: anaemia 0%, neutropenia 25%, thrombocytopenia 22%) was significantly influenced by the high percentage of pts. with BM infiltration and concomitant cytopenia on entry to the trial. The most common non-haematological adverse events were fatigue (76%), nausea (56%), diarrhoea (56%), lethargy (46%). Neurotoxicity occurred in 19 pts. (46%) (10 pts. grade 1, 7 pts. grade 2, 2 pts. grade 3). Btz dose was reduced in 7 pts.; 5 doses were omitted because of neuro or haematological toxicity. In 16 pts., treatment was delayed by 1-14 days and in 24 pts. treatment was stopped prematurely. The reasons for stopping treatment were: treatment-related toxicity 11 pts., progressive disease 9 pts., patient’s preference 3 pts., myocardial infarction 1 pt. One pt. was excluded having been found ineligible post randomisation. Thirty-nine pts. (21 arm A, 18 arm B) are evaluable for response so far, one having only received 1 cycle of therapy, which had to be discontinued because of excessive toxicity. 15/32 were in remission (CR, CRu, PR) at the completion of therapy, 7/7 at “mid-therapy” assessment, and 5 have yet to be evaluated. Thus the overall response rate (RR) presently is 22/39 (56%) (CR, CRu, PR), FL 44%, MCL 46%, WM 90%. Conclusions: The combination was active in pts. with recurrent NHL especially WM (RR 90%), despite multiple previous treatments, The weekly schedule is preferable being more convenient, as efficacious and no more toxic. Further investigation is warranted, despite not insignificant therapy compromising toxicity.

Introduction: Rituximab (R) is an integral component of therapy for B-cell lymphoid malignancies; bortezomib (Btz) has shown provocative single agent activity in Follicular Lymphoma (FL), Mantle Cell Lymphoma (MCL) and Waldenström's Macroglobulinaemia (WM), providing the rationale for investigating the combination.