Neuronal vacuole formation in the rat posterior cingulate/retrosplenial cortex after treatment with the N-methyl-d-aspartate (NMDA) antagonist MK-801 (dizocilpine maleate)

Cytoplasmic vacuoles appear in neurons of the posterior cingulate/retrosplenial cortex (PC/RS) of rats after treatment with N-methyl-d-aspartate (NMDA) receptor antagonists. Prominent dilatation of mitochondria and endoplasmic reticulum has been described within 2 h; however, the ultrastructural features of vacuole formation are unknown. To investigate this, the present study examined the PC/RS cortex of male rats (age 60–70 days) at 15, 30, 45, 60, 90, and 120 min after subcutaneous treatment with 1 mg/kg of the noncompetitive NMDA antagonist MK-801 (dizocilpine maleate, 5-methyl-10, 11-dihydro-5H-dibenzo [a,d] cyclohepten-5,10-imine). Subtle mitochondrial dilatation was identified in a few neurons as early as 15 min postdose (MPD). By 30 MPD, dilatation was more pronounced in mitochondria and also involved the endoplasmic reticulum and perinuclear space. Ribosomal disaggregation and degranulation were also evident by 30 MPD. At all subsequent time points, dilatation of mitochondria and endoplasmic reticulum progressed in severity. Although the relative involvement of mitochondria and endoplasmic reticulum varied, glia were not involved. These ultrastructural data suggest that after treatment with MK-801, mitochondrial dilatation precedes involvement of endoplasmic reticulum in vacuolization of susceptible PC/RS cortical neurons. The early mitochondrial effects identified in this study suggest an initial metabolic insult that rapidly progresses to affect endoplasmic reticulum and ribosomes. This strengthens the relationship between the ability of certain NMDA antagonists to induce energy perturbations and neuronal vacuoles in the same region of the rat cerebral cortex.     

Drug mixture which improves survival of ischemic rabbit epigastric skin flaps

The chief aim of this study was to maximize flap survival by counteracting the pathophysiological changes occurring during ischemia-reperfusion. Rabbit epigastric skin flaps given 21 hours of ischemia were infused intra-arterially with selected drugs at the start of reperfusion. Compared with control infused ischemic flaps, which had a 33% survival rate on day 7 post-ischemia, significant improvement was found with vasodilators nitrendipine (61%) and prostacyclin (65%) and the thrombolytic agent urokinase (65%); marginal improvement with the free radical scavenger desferrioxamine (53%); but no change with streptokinase (44%), heparin (21%), and ATP-MgCl₂ (35%). A drug mixture comprising all of these agents except streptokinase and urokinase produced 87% survival, suggesting an additive effect. Biochemical assays on skin homogenates and blood implicated oxygen free radicals, neutrophil infiltration, and thromboxane in flap failure. These results imply that multiple factors are responsible for ischemic flap failure and that a mixture of drugs needs to be infused to counteract all of the detrimental changes. © 1994 Wiley-Liss, Inc.     

Anesthesia and/or Sedation for Pulsed Dye Laser Therapy

One of the most exciting developments in pediatric dermatology has been the use of the flashlamp-pumped, 585-nm, pulsed dye laser for treatment of vascular birthmarks. In many cases the results are miraculous. The increase in self-esteem and happiness of many children and adolescents has been overwhelming; for some, depression has been lifted, stuttering has ceased, social involvement has increased, and antidepressants have been discontinued. There are many success stories to tell.
Despite the remarkable effects of the pulsed dye laser and the medical and psychosocial indications for its use, the issue of pain control remains significant. We have no perfect outpatient pediatric anesthetic. Most methods carry either some risk or, if not hazardous, often are not very effective for controlling pain. Needless to say, a diversity of opinions exist on how to manage discomfort from this treatment modality. Therefore, we thought it would be useful to share the experiences and opinions of several dermatologists who have extensive experience with the pulsed dye laser.     

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.     

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.