Behavioral dissociation of anterodorsal and posteroventral hippocampus by subseizure stimulation in mice

BALB/c mice were bilaterally implanted with bipolar electrodes either in anterodorsal (ADH) or posteroventral hippocampus (PVH) in order to compare the effects of postsession electrical stimulation on memory processes. For each experiment, 30 s after the end of the first session, the animals were stimulated during 80 s. For both hippocampal regions, the stimulation intensity was half of the afterdischarge threshold value. Control groups were naive, ADH and PVH implanted non-stimulated animals. Different appetitive and aversive tasks were used. Subseizure stimulation never created a deficit. Depending on the region of the hippocampus stimulated and on the learning task, a retention enhancement was eventually observed. These data are in agreement with the involvement of hippocampus in initial stages of memory consolidation. Further, the subseizure stimulation permitted a functional dissociation between the two hippocampal regions. Both regions seemed involved in the integration of information, but the anterodorsal part would be rather related to behavioral inhibition, while the posteroventral part would have the capacity to induce an arousal state allowing behavioral flexibility.     

Model Features of a Cardiac lontophoretic Drug Delivery Implant

Pharmaceutical Research -     

Acute effects of the ampakine farampator on memory and information processing in healthy elderly volunteers.

Ampakines act as positive allosteric modulators of AMPA-type glutamate receptors and facilitate hippocampal long-term potentiation (LTP), a mechanism associated with memory storage and consolidation. The present study investigated the acute effects of farampator, 1-(benzofurazan-5-ylcarbonyl) piperidine, on memory and information processes in healthy elderly volunteers. A double-blind, placebo-controlled, randomized, cross-over study was performed in 16 healthy, elderly volunteers (eight male, eight female; mean age 66.1, SD 4.5 years). All subjects received farampator (500 mg) and placebo. Testing took place 1 h after drug intake, which was around Tmax for farampator. Subjects performed tasks assessing episodic memory (wordlist learning and picture memory), working and short-term memory (N-back, symbol recall) and motor learning (maze task, pursuit rotor). Information processing was assessed with a tangled lines task, the symbol digit substitution test (SDST) and the continuous trail making test (CTMT). Farampator (500 mg) unequivocally improved short-term memory but appeared to impair episodic memory. Furthermore, it tended to decrease the number of switching errors in the CTMT. Drug-induced side effects (SEs) included headache, somnolence and nausea. Subjects with SEs had significantly higher plasma levels of farampator than subjects without SEs. Additional analyses revealed that in the farampator condition the group without SEs showed a significantly superior memory performance relative to the group with SEs. The positive results on short-term memory and the favorable trends in the trail making test (CTMT) are interesting in view of the development of ampakines in the treatment of Alzheimer's disease and schizophrenia.     

Gingival salivary gland choristoma

A unique example of a gingival salivary gland choristoma together with a gingival cyst is described in a human autopsy specimen of periodontal tissues. A choristoma is a tumor-like growth which is derived from primordial cells which have been displaced from their original tissue or organ. Only 6 other examples of the gingival salivary gland choristoma have been described in the world literature.     

Update on managing hypercholesterolemia. The new NCEP guidelines.

1. The Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (ATPIII) will significantly increase the number of Americans treated for hypercholesterolemia. 2. The ATPIII focuses on lowering low density lipoprotein cholesterol as a primary initiative and using exercise, diet, and pharmacotherapy as a means for lowering coronary heart disease and risks. 3. The new guidelines list low density lipoprotein cholesterol levels of less than 100 mg/dL as optimal for all clients. 4. The ATPIII places increased attention on high triglyceride levels (> 200 mg/dL) and on early detection and appropriate aggressive treatment for clients at risk for coronary heart disease and events.     

Human xenoreactive natural antibodies of the IgM isotype activate pig endothelial cells

Abstract: Preformed, xenoreactive natural antibodies (XNA) and complement (C) are involved in the initiation of vascular rejection of organs transplanted between discordant species, presumably by stimulating donor organ endothelial cells (EC). Although C is known to play a role in the activation of EC, it has not been clear whether the antibodies serve only to anchor the initial components of C, and thus permit the C cascade to proceed, or whether the antibodies themselves deliver a signal to the EC. We have tested affinity-purified human IgM containing XNA (IgM-XNA) for its ability to stimulate in vitro the up-regulation of genes in pig EC. Northern blot analysis shows that IgM, which contains XNA, stimulates mRNA accumulation for certain genes (including IL-8, PAI-1, and ECI-7, a new gene that we have found is associated with EC activation), but not others known to be up-regulated in response to TNF, IL-1 or LPS. Our results show that XNA provide a signal to EC, and thus may themselves participate in activation of EC and consequent vascular rejection.