Recovery from ischemic brain injury in the rat following a 10 h delayed injection with MLN519

In the present study, we evaluated delayed treatment effects of the proteasome inhibitor and anti-inflammatory agent MLN519 (initiated 10 h post-injury) to improve recovery following ischemic brain injury in rodents. Male rats were exposed to 2 h of middle cerebral artery occlusion (MCAo) and treated with MLN519 (1.0 mg/kg, i.v. @ 10, 24, and 48 h post-occlusion) or vehicle. By 2 weeks post-injury, 60% (6/10) of vehicle animals survived, which was improved (although non-significantly) to 78% (7/9) following MLN519 treatment. The percent loss of tissue in the ipsilateral brain hemisphere (at 2 weeks) was significantly reduced from 27+/-4% (vehicle) to 15+/-4% (MLN519). MLN519 treated animals also lost significantly less body weight (39%) and showed significant improvement in overall neurological function across the 2-week recovery period. However, no significant treatment effects were observed to reduce foot-fault deficits (balance beam) or improve recovery of operant performance (active avoidance test). Overall, delayed treatment with MLN519 provided significant improvement in 3 of 6 test metrics (histopathology, body weight, and neurological dysfunction) supporting improved outcome for brain-injured subjects.     

Effects of physostigmine and human butyrylcholinesterase on acoustic startle reflex and prepulse inhibition in C57BL/6J mice

The use of exogenously administered cholinesterases as bioscavengers of highly toxic organophosphorus nerve agents is a viable prophylactic against this threat. To use this strategy, cholinesterases must provide protection without disrupting behavior when administered alone. To assess behavioral safety, the acoustic startle reflex and prepulse inhibition (PPI) of C57BL/6J mice were investigated following administration of human plasma-derived butyrylcholinesterase (HuBChE). Two hours before testing, four groups of mice (n=10 per group) were pretreated with saline or HuBChE (2000 U, ip). Fifteen minutes before testing, subjects received either saline or the carbamate physostigmine (0.4 mg/kg, sc). Mice exposed to physostigmine exhibited a significant attenuation of the startle reflex, an increased time to peak startle amplitude, and significantly increased PPI. This effect was partially mitigated in mice pretreated with HuBChE. HuBChE alone did not change startle behavior or PPI significantly compared to saline controls. The circulatory time-course of butyrylcholinesterase was assessed in a separate group of mice and revealed levels approximately 600 times the physiological norm 2-4 h post administration. Thus, HuBChE does not appear to significantly alter startle or PPI behavior at a dose 30-fold higher than that estimated to be necessary for protection against 2LD50 of soman in humans.     

Drinking to cope: a comparison of questionnaire and electronic diary reports

OBJECTIVE: The purpose of this article is to assess the correspondence between questionnaire reports of dispositional drinking to cope (DTC) and different indices of daily DTC in a sample of nondependent heavy drinkers. METHOD: Data from electronic diary (ED) records of interpersonal problems, negative affect, coping and drinking were used to examine how questionnaire reports of dispositional DTC corresponded to ED reports of daily DTC and to within-person associations among ED reports of negative affect, interpersonal problems and drinking. In the current study, 98 community-residing heavy drinkers using EDs recorded moods, interpersonal problems, coping attempts, desire to drink and drinking for 21 consecutive days. RESULTS: The findings demonstrate correspondence between questionnaire reports of dispositional DTC and (1) ED reports of daily DTC, (2) intensity of negative mood associated with daily drinking initiation and (3) some between-person differences in within-day prediction of drinking and desire to drink from mood and interpersonal problem ratings. Those reporting higher dispositional DTC were somewhat more likely to drink in response to some negative moods and less likely to drink in response to some positive moods than those reporting relatively lower dispositional DTC, but these findings were mixed. CONCLUSIONS: Questionnaire reports of dispositional DTC are at best inconsistently linked to observed within-person associations among daily moods, interpersonal problems and drinking even among heavy drinkers.     

Utilization of screening mammography in New Hampshire: a population-based assessment

BACKGROUND: The objective of screening mammography is to identify breast carcinoma early, which requires routine screening. Although self-report data indicate that screening utilization is high, the results of this population-based assessment indicated that utilization is lower than reported previously. METHODS: The authors compared New Hampshire population data from the 2000 Census with clinical encounter data for the corresponding time obtained from the New Hampshire Mammography Network, a mammography registry that captures approximately 90% of the mammograms performed in participating New Hampshire facilities. RESULTS: The results showed that approximately 36% of New Hampshire women either never had a mammogram or had not had a mammogram in > 27 months (irregular screenees), and older women (80 yrs and older) were less likely to be screened (79% unscreened/underscreened) compared with younger women (ages 40-69 yrs; 28-32% unscreened/underscreened). Of the screened women, 44% were adhering to an interval of 14 months, and 21% were adhering within 15 months and 26 months. The remaining 35% of the women had 1 or 2 mammograms and did not return within 27 months. CONCLUSIONS: Routine mammography screening may be occurring less often than believed when survey data alone are used. An important, compelling concern is the reason women had one or two mammograms only and then did not return for additional screening. This area deserves additional research.