Transient 23-30 Hz oscillations in mouse hippocampus during exploration of novel environments

The hippocampus is a key brain structure for the encoding of new experiences and environments. Hippocampal activity shows distinct oscillatory patterns, but the relationships between oscillations and memory are not well understood. Here we describe bursts of hippocampal approximately 23-30 Hz (beta2) oscillations in mice exploring novel, but not familiar, environments. In marked contrast to the relatively invariant approximately 8 Hz theta rhythm, beta2 power was weak during the very first lap of the novel environment, increased sharply as the mice reencountered their start point, then persisted for only a few minutes. Novelty-evoked oscillations reflected precise synchronization of individual neurons, and participating pyramidal cells showed a selective enhancement of spatial specificity. Through focal viral manipulations, we found that novelty-evoked oscillations required functional NMDA receptors in CA3, a subregion critical for fast oscillations in vitro. These findings suggest that beta2 oscillations indicate a hippocampal dynamic state that facilitates the formation of unique contextual representations.     

Intestinal transport of aminopterin enantiomers in dogs and humans with psoriasis is stereoselective: evidence for a mechanism involving the proton-coupled folate transporter

N-[4-[[(2,4-diamino-6-pterdinyl)methyl]amino]benzoyl]-l/d-glutamic acid (l/d-AMT) is an investigational drug in phase 1 clinical development that consists of the l-and d-enantiomers of aminopterin (AMT). l/d-AMT is obtained from a novel process for making the l-enantiomer (l-AMT), a potent oral anti-inflammatory agent. The purpose of these studies was to characterize oral uptake and safety in the dog and human of each enantiomer alone and in combination and provide in vitro evidence for a mechanism of intestinal absorption. This is the first report of l /d-AMT in humans. In dogs (n = 40) orally dosed with l-AMT or d-AMT absorption was stereoselective for the l-enantiomer (6- to 12-fold larger peak plasma concentration after oral administration and area under the plasma concentration-time curve at 0-4 h; p < 0.001). d-AMT was not toxic at the maximal dose tested (82.5 mg/kg), which was 100-fold larger than the maximal nonlethal l-AMT dose (0.8 mg/kg). Dogs (n = 10) and humans with psoriasis (n = 21) orally administered l-AMT and l /d-AMT at the same l-enantiomer dose resulted in stereoselective absorption (absent d-enantiomer in plasma), bioequivalent l-enantiomer pharmacokinetics, and equivalent safety. Thus, the d-enantiomer in l/d-AMT did not perturb l-enantiomer absorption or alter the safety of l-AMT. In vitro uptake by the human proton-coupled folate transporter (PCFT) demonstrated minimal transport of d-AMT compared with l-AMT, mirroring the in vivo findings. Enantiomer selectivity by PCFT was attributable almost entirely to decreased binding affinity rather than changes in transport rate. Collectively, our results demonstrate a strong in vitro-in vivo correlation implicating stereoselective transport by PCFT as the mechanism underlying stereoselective absorption observed in vivo.     

Age and practice effects in continuous recognition memory

Older and younger women identified new and repeated items in extended lists of letter-number combinations (e.g., "A42G"). Repeated items occurred at intervals ranging from 0 to 32 items (0 to 160 s) and for different lists the items were either visual or auditory. The older women's performances declined at a more rapid rate as the retention interval was increased. When the older women practiced the auditory task, performances improved and gains transferred to the visual task. Gains by the younger women were equivalent, so that initial age differences were maintained. Signal detection analyses attributed age effects to differences in sensitivity rather than bias. For women of both ages, conservative bias was greater when the intervals were long and when the task was visual. The absence of age-bias effects was contrary to the hypothesis that older adults adopt more conservative decision strategies. The presence of sensitivity differences, even when the task was well practiced, suggests fundamental age differences in recognition memory.     

Transtympanic ventilator tubes in the treatment of seromucous otitis. Indications and results.

400 patients with bilateral secretory otitis media (SOM) were treated with ventilating tubes (VT) in a prospectiv study. The ear drums were normal on both sides before VTs treatment thus allowing ear drum changes and complications during VT treatment to be recorded. 618 VT were placed in the ear drum after suction of the fluid. In 182 patients unilateral myringotomy with suction of fluid were done and VT placed in the contralateral ear. Adenoidectomy with myringotomy, with an obstructing adenoid, gave 30% better chance. 10 different VTs were used. The most frequent pathology found in the ear drum after one period of VT treatment was tympanosclerosis. In the ears only treated with myringotomy tympanosclerosis occurred in 1%. 3 factors seemed to give more tympanosclerosis: metal (stainless steel or titanium), polyethylene and prolonged stay-time in the ear drum. Chronic perforations of the ear drum occurred with great variations between the different tubes. The Goode modified T-tube caused perforations in 17%. In the other VTs the perforations occurred in 2.1%. Chronic perforation together with tympanosclerosis will happen more often when the VT is made of polyethylene compared to silicone or fluoroplastic (p < 05). 90% of the perforations were located at the site of the VT. The ideal VT will stay in for 8-18 months at an average and it can be shown to improve middle ear function better than only waiting or myringotomy. Long-term VTs should not be used at the first VT procedures.     

Relative reliability of three different discriminant analysis methods for detecting PKU gene carriers

A previously derived discriminant function for detecting classical PKU gene carriers without a priori pedigree probability was reevaluated using a large sample size. The test involves fluorometric measurement of fasting phenylalanine and tyrosine plasma levels. Among 75 controls and 45 known carriers, 95% could be classified as to their carrier status with greater than 98% accuracy. The accuracy of our method in classifying our population compared favorably to that of two other discriminant analysis methods requiring a priori probability.