Combined treatment with galanthaminium bromide,a new cholinesterase inhibitor,and RS 67333, a partial agonist of 5-HT4 receptors,enhances place and object recognition in young adult and old rats

The present study was designed to investigate whether a combination of a new acetylcholinesterase inhibitor we have synthesized, galanthaminium bromide, and an agonist of 5-hydroxytryptamine(4) receptors, RS 67333, at doses ineffective alone, improves performance in tasks involving place and object recognition memory. Dose responses of each compound were determined in order to select doses without effect alone. Accordingly, young adult rats were injected intraperitoneally with galanthaminium bromide (0.3 mg/kg)+RS 67333 (0.01 mg/kg), and old rats with galanthaminium bromide (0.1 mg/kg for place and 0.3 mg/kg for object recognition)+RS 67333 (1 mg/kg). Drugs were injected before the acquisition phase, immediately after it, or before the retrieval phase to determine the stage of information processing affected by treatments. Doses of galanthaminium bromide and RS 67333, without effect on their own, jointly improved both place and object recognition in young adult rats via an enhancement of acquisition and consolidation information processing. In old rats, the combined treatment enhanced performance by acting on the acquisition processes of place recognition and on the acquisition and consolidation processes of object recognition. These results indicate that combining agents that act on different neuronal targets may be more powerful than either treatment alone, enabling use of lower doses of each compound, thereby attenuating the adverse effects of the individual drugs. A bitherapeutic strategy of this kind might thus be of interest in the treatment of the cognitive deficits related to "normal" or pathological aging.     

Are late-onset schizophrenia spectrum disorders neurodegenerative conditions? Annual rates of change on two dementia measures

Some investigators assert that emergence of schizophrenia spectrum disorders in mid- to late life (LOSD, i.e., onset after age 45) reflects neurodegenerative processes. The authors examined 1- and 2-year changes among 37 outpatients with LOSDs on the Mini-Mental State Examination (MMSE) and Mattis Dementia Rating Scale, compared with 69 patients having earlier-onset schizophrenia spectrum disorders (EOSD), 67 having Alzheimer's disease (AD) with psychosis, 72 having AD with baseline MMSE scores >/=24, and 56 normal comparison subjects (NCs). Cognitive changes among LOSD patients were similar to those in EOSD patients and NCs, whereas the AD groups had greater declines. Results support viewing LOSDs as static encephalopathies.     

Effect of sleep deprivation on the performance of simulated laparoscopic surgical skill

BACKGROUND: Resident work hours may impact patient care. We hypothesized that "call-associated" acute sleep deprivation has no effect on technical dexterity as measured on a minimally invasive surgery trainer, virtual reality (MIST VR) surgical simulator. METHODS: Thirty-five surgical residents were prospectively evaluated pre-call (rested), on-call (rested), and post-call (acutely sleep deprived). Participants completed questionnaires regarding sleep hours and level of fatigue. Technical skill was assessed using the MIST VR. Speed, errors, and economy of motion were automatically recorded by the MIST VR computer simulator. Data were analyzed by paired Student t test and analysis of variance. RESULTS: Estimated hours of sleep and subjective indicators of fatigue were different between rested and sleep-deprived residents. The number of errors and time to complete all tasks increased at the post-call assessment. CONCLUSIONS: Resident work schedules lead to sleep deprivation and fatigue. Call-associated sleep deprivation and fatigue are associated with increased technical errors in the performance of simulated laparoscopic surgical skills.     

Genetic association of acyl-coenzyme A: cholesterol acyltransferase with cerebrospinal fluid cholesterol levels,brain amyloid load,and risk for Alzheimer's disease

A common polymorphism of the gene encoding acyl-coenzyme A: cholesterol acyltransferase 1 (SOAT1), which is involved in the regulation of beta-amyloid peptide generation, is associated with low brain amyloid load (P=0.03) and with low cerebrospinal fluid levels of cholesterol (P=0.005). This polymorphism of SOAT1 is also associated with reduced risk for Alzheimer's disease in ethnically distinct populations (P=0.0001, odds ratio: 0.6, 95% confidence interval 0.4-0.8).     

THE SITE OF ACTION OF THE STAPHYLOCOCCUS ALPHA TOXIN

The present study concerns the site of action of the staphylococcus alpha toxin. This powerful necrotizing agent produced by pathogenic strains of staphylococcus is very probably important in the pathogenesis of localized staphylococcus disease and in the shock-like picture sometimes associated with staphylococcus septicemia. Our previous studies had suggested that the toxin has a selective effect on vascular smooth muscle. In investigating this problem further, the following observations were made. 1. The toxin produces an immediate hyperperistalsis and sustained increase in intraluminal tension progressing ultimately to atony and flaccid paralysis in the isolated smooth muscle preparation. 2. The addition of specific antitoxin prior to exposure to toxin prevents this reaction. However, when antitoxin is added after the toxin, no ameliorating effect is seen. 3. The toxin is rapidly and irreversibly bound to its substrate since washing the bowel segment 30 seconds after exposure to toxin fails to change the course of the reaction. 4. Vena caval segments exposed to toxin exhibit a similar initial rise in intraluminal tension followed by flaccid paralysis at which point they no longer respond to epinephrine stimulation. 5. When the toxin is infiltrated in the neighborhood of muscular blood vessels in the living rabbit selective necrosis of smooth muscle cells of the vessel walls is seen. 6. The selective effect on smooth muscle is emphasized by the failure of the toxin to affect the contractility of skeletal and cardiac muscle. 7. Perfusion of the isolated kidney and heart produces an increased resistance to flow after toxin is added to the perfusate. 8. Epithelial cells and fibroblasts in tissue culture exposed to high concentration of toxin for 2 hours are unaffected in their ability to recover and metabolise. This is in marked contrast to the effect on the smooth muscle preparation. The probability that the toxic effect on smooth muscle cells explains some of the local and systemic effects of staphylococcus infection is discussed.