Dentate gyrus-selective colchicine lesion and disruption of performance in spatial tasks: difficulties in "place strategy" because of a lack of flexibility in the use of environmental cues?

The effects of intradentate colchicine injections on the performance of tasks requiring spatial working and reference memory are controversial. Multiple-site colchicine injections (7 microg/microl; via a drawn micropipette) throughout the dentate gyrus (DG) of rats (nine sites in each hemisphere, 0.06 microl at each site) selectively destroy about 90% of the DG granule cells, as revealed by quantitative stereological estimates; stereology also revealed minor neuronal losses in the CA4 (33%) and CA1 (23%) subfields, but lack of damage to the CA3 hippocampal subfield. Spatial reference and working memory were assessed in Morris' water maze; in the reference memory task, the rats were required to learn a single, fixed location for the platform over several days of training; in the working memory task, animals were required to learn a new platform location every day, in a matching-to-place procedure. Compared to sham-operated controls, lesioned rats showed significant disruption in acquisition of the reference memory water maze task; however, the data reveal that these rats did acquire relevant information about the task, probably based on guidance and orientation strategies. In a subsequent probe test, with the platform removed, lesioned rats showed disruption in precise indexes of spatial memory (e.g., driving search towards the surroundings of the former platform location), but not in less precise indexes of spatial location. Finally, the lesioned rats showed no improvement in the match-to-place procedure, suggesting that their working memory for places was disrupted. Thus, although capable of acquiring relevant information about the task, possibly through guidance and/or orientation strategies, DG-lesioned rats exhibit a marked difficulty in place strategies. This is particularly evident when these rats are required to deal with one-trial place learning in a familiar environment, such as in the working memory version of the water maze task, which requires flexibility in the use of previously acquired information.     

Tremor frequency patterns in mercury vapor exposure, compared with early Parkinson's disease and essential tremor

A new portable tremometer allows determination of tremor intensities at different tremor frequencies. Based on past studies, two tremor frequency windows of similar size were chosen at 3.0-6.5 Hz and 6.6-10.0 Hz to reflect major tremor intensities in Parkinson's disease and mercury vapor poisoning, respectively. In 81 healthy controls, total tremor intensity was higher for the preferred hand and depended on age. Ten patients treated for Parkinson's disease showed substantially increased tremor intensity, especially within the low-frequency window. This pattern was also apparent in 14 patients with de novo Parkinson's disease whose overall tremor intensity was only mildly elevated. In contrast, ten patients with essential tremor had peak frequencies in both windows, and some patients had increased tremor on one side only. Sixty-three Brazilian gold traders exposed to mercury vapor showed increased tremor predominantly in the high-frequency window. Three of the gold traders had a narrower tremor peak at frequencies of 7-8 Hz. While the urine-mercury concentration was significantly associated with the current number of burning sessions per week, it did not correlate with tremor intensities. However, eight traders had a urinary mercury excretion level above 50 microg and at the same time a greatly increased average tremor intensity within the high-frequency window. These patterns were statistically significant for relative tremor intensities, but were less clear when total intensities were used. These observations suggest that the relative distribution of tremor intensities in specific frequency bands may be a valuable supplement to current diagnostic methods for subjects with mercury vapor exposure.     

Effects of diazepam or haloperidol on convulsion and behavioral responses induced by bilateral electrical stimulation in the medial prefrontal cortex

1. Effects of diazepam (DZP) or haloperidol (HAL) on convulsions and behavioral responses (locomotion, circling, spying and head shaking) induced by bilateral electrical stimulation in the medial prefrontal cortex (mPFC) were examined. 2. Male Wistar rats were electrically stimulated (ten 30-sec trains, 60 Hz, 80-100 microA) bilaterally in the mPFC and their behavior was simultaneously observed in an open field in daily session. 3. DZP and HAL dose-response curves (0, 0.5, 1.25, 2.5 and 5 mg/kg, i.p., 30 min before electrical stimulation session) were determined after a baseline of behavioral responses was established. 4. DZP dose-dependently decreased head shaking and convulsions, had no effect in circling and spying behaviors, and increased locomotion except at the highest dose. HAL reduced locomotion, circling and spying behaviors in a dose-dependent manner, but did not affect convulsions or head shaking. 5. These results demonstrated that convulsion and behavioral responses induced by electrical activation of the mPFC were modified by DZP or HAL. Therefore, the mPFC is involved in the mediation of neural and/or behavioral activity that may be implicated in some central effects of psychoactive drugs.     

Long-term effects of finasteride on prostate tissue composition

OBJECTIVES: To determine the long-term effects of finasteride treatment on prostate tissue composition; to relate these effects to clinical outcomes; and to test the hypothesis that finasteride exerts a selective or preferential action on the transition zone. METHODS: Nineteen men with symptomatic benign prostatic hyperplasia (BPH) who completed a 6-month double-blind trial of finasteride were enrolled in a 24-month open-label extension study of drug responders. Magnetic resonance imaging and prostate biopsy for morphometric analysis were performed together 70 times: at baseline (n = 19), after treatment periods of intermediate duration (6 to 18 months, n = 32), and after long-term drug treatment (24 to 30 months, n = 19). At baseline, prostate volume averaged 51 cc, of which 57% was transition zone. RESULTS: Decreases in symptom score, dihydrotestosterone and prostate-specific antigen levels, and prostate volume occurred at 6 months (P <0.01), stabilized, and were maintained without further long-term decreases. Prostate epithelium contracted progressively from baseline (19.2% tissue composition; 6.0-cc volume; 3.2 stroma/epithelial ratio) to intermediate (12.5%, 3.3 cc, and 5.6, respectively) to long-term treatment (6.4%, 2.0 cc, and 17.4, respectively, P <0.01 for all). Percent epithelial contraction was similar in the peripheral and transition zones (P = NS). The transition zone remained a relatively constant proportion (53% to 58%) of whole-prostate volume from baseline to long-term observation. CONCLUSIONS: Long-term finasteride treatment (24 to 30 months) results in a marked involution of the prostate epithelium, which continues to progress for many months after clinical effects stabilize. The effect on the epithelium is similar in the peripheral and transition zones for both morphometric and volumetric changes. Progressive contraction of the prostate epithelium appears to constitute the underlying mechanism for sustained action of finasteride.     

A new method for monitoring the contamination of glycerol with diethylene glycol

A quartz crystal microbalance has been used to check the purity of glycerol. The experimental procedure involves no derivatization or other preliminary step except determination of water content. The protocol consists of the direct reading of the frequency of a quartz crystal with one face in contact with an aqueous solution of the glycerol to be tested. The method is inexpensive, simple, rapid, and highly sensitive; diethylene glycol contamination at the 3.61% level could be detected.     

Study of the antinociceptive action of the ethanolic extract and the triterpene 24-hydroxytormentic acid isolated from the stem bark of Ocotea suaveolens

We describe here the antinociceptive action of the crude extract (CE), the chemical isolation and characterisation and preliminary pharmacological analysis of 24-hydroxytormentic acid, isolated from the stem bark of Ocotea suaveolens (Lauraceae). The CE given by i.p. or p.o. routes, 30 min and 1 h prior, produced significant inhibition of abdominal constrictions caused by acetic acid and also inhibited both phases of formalin-induced licking in mice. The antinociception caused by the CE, given by i.p. and p.o. routes, lasted up to 4 and 2h, respectively. When assessed in the hot-plate test, the CE was inactive. Its antinociceptive action was not associated with non-specific effects such as muscle relaxation or sedation. The antinociception of CE was not influenced by naloxone, L-arginine or DL-p-chlorophenylalanine methyl ester, when assessed against the formalin assay. The triterpene 24-hydroxytormentic acid, given i.p. 30 min before testing, produced significant, dose-related and equipotent antinociceptive action against both phases of formalin-induced licking in mice. These results demonstrate, for the first time, the occurrence of the triterpene 24-hydroxytormentic acid in the stem bark of Ocotea suaveolens, and show that the CE and 24-hydroxytormentic acid exhibit marked antinociception against the neurogenic and the inflamamtory algesic responses induced by formalin in mice. The mechanism by which this compound and CE produces antinociception still remains unclear, but is unlikely to involve the activation of opioid, nitric oxide or serotonin systems or non-specific peripheral or central depressant actions.     

Grossamide and N-trans-caffeoyltyramine from Annona crassiflora seeds

Grossamide, and N-trans-caffeoyltyramine, were isolated for the first time from the seeds of Annona crassiflora Mart, and in the Annonaceae family.