Effects of N-(2,6-dimethylphenyl)-2-(2-oxo-1-pyrrolidinyl)acetamide (DM-9384) on learning and memory in rats

Effects of N-(2,6-dimethylphenyl)-2-(2-oxo-1-pyrrolidinyl) acetamide (DM-9384) on learning and memory were studied using four different experimental rat models. In electroconvulsive shock- or scopolamine-induced amnesia in the step-through passive avoidance task, DM-9384 improved both types of amnesia when administered before the training trial. Aniracetam also showed similar but somewhat weaker effects. Furthermore, in the scopolamine amnesia model, an improvement was confirmed with arecoline. The dose-response curves for these compounds were bell-shaped. In the shuttle box active avoidance task, DM-9384 administered daily 1 hr before each training session facilitated the acquisition process of the avoidance response. In addition, the experiment of light-dark discrimination task with positive reinforcement showed that this compound administered daily after each session slightly accelerated the acquisition process of the correct response. These results suggest an ability of DM-9384 to enhance cognitive functions.     

Allergic Predisposition Among Infants with Bronchiolitis

Allergic predisposition among infants with bronchiolitis was examined. The number of infants with serum IgE exceeding mean +1 SD was 31/70 (44.3%). The rate of positive radioallergosorbent test (RAST) scores of 1 or more to mites, egg white, or milk was 31/71 (43.7%) and that of scores over 2 was 11/71 (15.5%). Eosinophils and/or mast cells were found in their nasal smears on several occasions. These results indicated that allergic predisposition may be observed among infants with bronchiolitis.     

AlphaV beta3 (αvβ3) integrin inhibition reduces leukocyte–endothelium interaction in a pressure-induced reperfusion model

The leukocyte-endothelium interaction is known to contribute to reperfusion injury, which is considered to participate in the pathophysiology of pressure ulcers, and integrin alphaV beta3 (alphavbeta3) has been shown to mediate the processes of cellular adhesion in various types of cells. This study aims to clarify leukocyte behavior in our original microcirculatory pressure-induced reperfusion model, which can visualize the microcirculation in vivo. We also estimated the effect of alphavbeta3 integrin inhibition on the reduction of the leukocyte-endothelium interaction. Mice with dorsal skinfold chambers were divided into three groups: the baseline group (n=6), in which animals received no compression; the compression-reperfusion group (n=6), in which animals underwent 2-hour compression of the dorsal skin, followed by release, and the inhibitor-treated group (n=7), in which an alphavbeta3 inhibitor, CP4715, was administered in addition to the compression-release procedure. Staining with rhodamine 6G quantitatively visualized leukocyte behavior under the intravital fluorescent microscope. Compression-reperfusion induced a significant increase in rolling, sticking, and extravasation of the leukocytes. Treatment with the inhibitor strikingly reduced leukocyte sticking and extravasation. The present experiment has provided evidence that alphavbeta3 inhibition reduces leukocyte-endothelium interaction in our original pressure-induced reperfusion model.     

Influence of Chewing and Clenching on Salivary Cortisol Levels as an Indicator of Stress

PURPOSE: The purpose of this study was to investigate the effects of chewing and clenching on salivary cortisol levels as an indicator of stress. MATERIALS AND METHODS: Seventeen healthy dentulous subjects were given arithmetic exercises to perform within a 20-minute time limit in order to elicit stress (stress loading). In the first experiment (chewing), after stress loading, the subjects were asked to chew a paraffin wax while reading printed material (books, magazines, etc.) in silence for 10 minutes. The same procedure was then carried out again for control purposes, but this time the subjects were not required to chew wax. In the second experiment (light clenching), after stress loading, the subjects were required to carry out 5 seconds of light clenching followed by 5 seconds of rest repeatedly over a 3-minute period. The whole 3-minute process was repeated a total of three times. The control data for this second experiment consisted of measurements taken during the rest periods. Saliva specimens were collected in both experiments both before stress loading and after each procedure during 1-minute intervals to measure cortisol levels. RESULTS: In the chewing experiment, salivary cortisol levels were significantly reduced by chewing, compared with those in the controls (p < 0.05). This reduction in salivary cortisol was observed during chewing over a 10-minute period following stress loading. In the clenching experiment, salivary cortisol levels also showed a significant reduction during clenching, compared with those in the controls (p < 0.05). CONCLUSIONS: These results suggest that chewing and clenching promote relaxation in subjects under stress.     

Self-expandable metallic stent for unresectable malignant strictures in the esophagus and cardia

Objective Self-expandable metallic stent (EMS) placement has been the first choice for dysphagia because of the certainty over its safety, low invasiveness, and immediate efficacy. However, there still remain some problems in relation to the EMS placement site and anticancer therapies before and after EMS placement. Methods: Consecutive 78 patients in whom EMS was placed due to the unresectable malignant stricture in the esophagus or cardia from July 1995 to August 2003 in our department were studied. Results: Gastroesophageal reflux was found in 5 of 8 patients after placement of conventional EMS for the stricture in the gastroesophageal junction. Meanwhile, acid and bile reflux into the esophagus were not detected by pH and bilirubin monitoring, respectively, in 6 patients after placement of the EMS with an anti-reflux mechanism for the stricture in the gastroesophageal junction. The median survival period of all patients after EMS placement was 123 days. The median survival period of 7 patients with radiotherapy only after EMS placement was 138 days and that of 17 patients with radiotherapy before EMS placement was 60 days, which was shorter than that of the former (p<0.05). On the other hand, the median survival period after hospital admission due to dysphagia of these 7 patients was longer than that of 17 patients with radiotherapy only before EMS placement, although, the difference was not significant. Conclusion: EMS with an antireflux mechanism is not commercially available in Japan and approval is urgently required. The indication of radiotherapy associated with EMS placement is to be studied further.     

Invasive techniques for the diagnosis of respiratory infectious diseases

Conclusion Reviewing the history of diagnostic procedures of causative organisms of respiratory infections, invasive techniques such as the protected specimen catheter (PSB) and bronchoalveolar lavage (BAL) have become the preferred choices because they have many advantages. These methods cause the patient relatively little discomfort, and permit an early diagnosis since they can easily be performed at the bedside and the causative organism from the disease site is obtained in cultures. These procedures can be used not only in patients with community-acquired lung infections, but also in immunocompromised hosts, including those with blood diseases or following renal transplantation, in patients in intensive care units and in mechanically-ventilated patients so that the cause can be accurately determined and chemotherapy started quickly, resulting in better therapeutic efficacy. Although these invasive procedures are advantageous for the diagnosis of respiratory infections, they also present various problems which remain to be addressed including minimizing contamination and setting diagnostic threshold values. However, the importance of accurately determining the causative organism in respiratory infections should be recognized as the most important factor, and these methods have shown to date to provide the most accurate information to aid in the timely treatment of respiratory infections in a wide variety of patients.     

An estimation of a model explaining the mechanism causing neurotic disorders using a theory of fuzzy sets

Constructing and estimating a model to explain the mechanism of neurotic disorders is important and significant. The model helps the rearrangement or representation of knowledge obtained from professional physicians. However, it is a very difficult problem, because the objects requiring analysis are mental activities of human beings, and they originally include a comparatively large variance between individuals. The object data were obtained from patients with neurotic disorders who were diagnosed by several doctors for 10 years in a subagricultural areas in Japan. We analyzed the data and calculated the weights attached for personal information depending upon the similarity between the information and the kinds of neurotic disorders using the theory of fuzzy sets. From the results of our analysis, we constructed and estimated a model explaining the mechanism causing neurotic disorders as several linear equations. From data processing points of view, the estimation we attempted is placed in a kind of effective data compression with respect to discrete statistical data.     

A novel cognition enhancer NS-105 modulates adenylate cyclase activity through metabotropic glutamate receptors in primary neuronal culture

The effect of (+)-5-oxo-D-prolinepiperidinamide monohydrate (NS-105), a novel cognition enhancer, on adenylate cyclase activity was investigated in cultured neurons of the mouse cerebral cortex. NS-105 (10^–7 and 10^–6 M) inhibited forskolin-stimulated cyclic AMP formation, an action that was dependent on pertussis toxin-sensitive G proteins. Conversely, in pertussis toxin-pretreated neurons, NS-105 (10^–7 –10^–5 M) significantly enhanced the forskolin-stimulated cyclic AMP formation, and this action was completely reversed by cholera toxin. A metabotropic glutamate receptor agonist (1S, 3R)-1-aminocyclopentane-1, 3-dicarboxylic acid (1S, 3R-ACPD) produced similar bi-directional actions on the cyclic AMP formation. Both of these inhibitory and facilitatory actions of NS-105 and 1S, 3R-ACPD were blocked by L(+)-2-amino-3-phosphopropinoic acid (L-AP3). NS-105 (10^–6 M) and 1S, 3R-ACPD (10^–4 M) significantly enhanced isoproterenol- and adenosine-stimulated cyclic AMP formation. The enhancement of such Gs-coupled receptor agonists-stimulated cyclic AMP formation was also produced by quisqualate but not by L(+)-2-amino-4-phosphonobutanoate (L-AP4). The phosphoinositides hydrolysis was enhanced by 1S, 3R-ACPD (10^–4 M) but not by NS-105 (10^–6 M), however, 1S, 3R-ACPD-induced increase in phosphoinositides turnover was attenuated by NS-105. These findings suggest that NS-105 stimulates metabotropic glutamate receptor subclasses that are coupled both negatively and positively to adenylate cyclase, but it acts as an antagonist at the receptor subclasses that are linked to phosphoinositides hydrolysis. Received: 3 February 1997 / Accepted: 25 April 1997