Synthesis of a novel series of benzocycloalkene derivatives as melatonin receptor agonists

We synthesized a novel series of benzocycloalkene derivatives and evaluated their binding affinities to melatonin receptors. To control the spatial position of the amide group, one of the important pharmacophores, we incorporated an endo double bond, an exo double bond (E- and Z-configurations), and a chiral center (R- and S-configurations) at position 1. The indan derivatives with the S-configuration at position 1 were the most promising in terms of potency and selectivity for the human melatonin receptor (MT(1) site), while compounds with the R-configuration showed little potential. Our next attempt was to investigate the most favorable conformation of the methoxy group, the other important pharmacophore for binding to the MT(1) receptor. The introduction of a methyl group at position 5 of the indene ring conserved affinity; however, at position 7, it caused a decrease in affinity. These results suggested that the substitution at position 7 forced the methoxy group to adopt an unfavorable orientation. The optimization of the condensed ring size and substituents led to (S)-8d [(S)-N-[2-(2,3-dihydro-6-methoxy-1H-inden-1-yl)ethyl]propionamide], which had high affinity for the human MT(1) receptor (K(i) = 0.041 nM) but no significant affinity for the hamster MT(3)receptor (K(i) = 3570 nM). In addition, a practical synthetic method of chiral N-[2-(2,3-dihydro-1H-inden-1-yl)ethyl]alkanamides employing asymmetric hydrogenation with (S)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl-Ru has been established.     

Prediction of short-term progression or regression of atherosclerotic coronary artery disease by lipoprotein (a): a quantitative coronary angiographic study

This study assessed whether progression of coronary artery atherosclerotic lesions could be predicted in the short term using various lipid profiles. In 37 patients (61.9 +/- 9.5 years) undergoing coronary angioplasty and with 6-month follow-up angiography, quantitative coronary angiography of a new or changed lesion was performed in the follow-up examination, except for intervention vessels. The progression-regression score of the assessed lesion was calculated as the baseline minus the follow-up minimal lumen diameter. The serum lipoprotein (a) level was higher in the progression group (progression-regression score > 0.15 mm), than in the regression group (< or = -0.15 mm; p < 0.01) and the no change group (within +/- 0.15 mm; p < 0.05). Remnant-like lipoprotein particle-cholesterol and apolipoprotein-B levels were also higher in the progression group. However, multiple regression analysis of the progression showed that the progression-regression score was independently correlated with lipoprotein (a) alone (R = 0.50, p < 0.05). This shows that lipoprotein (a) is an independent predictor of coronary atherosclerotic lesion progression over the short term.     

Purkinje cell activity during learning a new timing in classical eyeblink conditioning

During classical eyeblink conditioning, animals acquire adaptive timing of the conditioned response (CR) to the interstimulus interval (ISI) between the conditioned stimulus (CS) and the unconditioned stimulus (US). To investigate this coding of the timing by the cerebellum, we analyzed Purkinje cell activities during acquisition of new timing after we shifted the ISI. Decerebrate guinea pigs were conditioned to an asymptotic level of learning using a delay paradigm with a 250-ms ISI. A 350-ms tone and a 100-ms electrical shock were used as the CS and US, respectively. As reported previously in other species, Purkinje cells in the simplex lobe exhibited three types of responses to the CS: excitatory, inhibitory, or a combination of the two. After we increased the ISI to 400 ms, the frequency of the CR stayed at an asymptotic level, but the latency of the CR peak became gradually longer. Two types of cells were observed, based on changes in the nature of their response to the CS; one changed its type of response in parallel with learning the new timing, while the other did not. There was no correlation between the type of response before and after we changed the ISI. In some cells, the peak latency of activities became longer or shorter, while the type of response did not change. These results suggest that some Purkinje cells code the timing of the CR, but do not play a consistent role in shaping the CR over a range of ISIs.     

Solcoseryl,a tissue respiration stimulating agent,significantly enhances the effect of capacitively coupled electric field on the promotion of bone formation around dental implants

In the present study we examined the combined effect of application of a capacitively coupled electric field (CCEF) and the tissue respiration stimulating agent, Solcoseryl, on the promotion of bone formation around dental implants histologically and mechanically. After a dental implant was inserted into each femur of Japanese white rabbits, Solcoseryl (2 ml/kg) was administered intravenously in the ear vein and a CCEF was applied for 4 h per day for 14 days. The degree of bone formation on microscopic observation, bone contact ratio, bone surface area ratio, and the level of removal torque of the implant in the Solcoseryl- and CCEF-treated group were significantly higher than the respective value in the control group, which had not been treated with Solcoseryl nor CCEF. Thus, the combination of CCEF stimulation and Solcoseryl effectively promoted the formation of new bone. It is suggested that the clinical use of a combination of CCEF stimulation and Solcoseryl for dental implants promotes osseointegration.     

Awake craniotomy with propofol sedation and a laryngeal mask airway: a case report

A 47-year-old man with brain tumor close to the speech center was scheduled for biopsy under awake craniotomy. Anesthesia was maintained with continuous infusion of propofol and intermittent fentanyl. Airway was secured with a laryngeal mask throughout the surgery. During cortical stimulation, his phonation was clear and there was no evidence of hypoxia.     

Effects of olprinone hydrochloride on intraocular pressure and ocular blood flow in patients after cardiac surgery under cardiopulmonary bypass

BACKGROUND: We evaluated the effect of olprinone hydrochloride on intraocular pressure (IOP) and ocular blood flow in patients after cardiac surgery under cardiopulmonary bypass (CPB). METHODS: Nine patients after cardiac surgery under CPB were investigated. We measured IOP of the left eye using tonometer (Tonopen XL, BIO RAD, Osaka), and mean blood flow velocity in the left ophthalmic artery (Vm) and calculated the pulsatility index in the left ophthalmic artery (PI) using 2 MHz Doppler ultrasound system (Multidop P, DWL, Germany). After baseline measurement, the olprinone hydrochloride loading dosage was increased from 0.15 to 0.3 microgram.kg-1.min-1 every 60 minutes. The intraocular pressure and ocular blood flow were measured at each point. RESULTS: IOP and PI decreased significantly, and Vm increased significantly at the infusion rate of 0.3 microgram.kg-1.min-1 from baseline. There was a significant linear correlations between IOP and Vm. CONCLUSION: We demonstrated that olprinone hydrochloride led to a decrease in IOP and an increase in ocular blood flow in patients after cardiac surgery under CPB.     

Time-limited role of the hippocampus in the memory for trace eyeblink conditioning in mice

We examined the role of the hippocampus in memory retention after trace eyeblink conditioning in mice. After establishing the conditioned response (CR) in the trace paradigm, mice received a bilateral aspiration of the dorsal hippocampus and its overlying neocortex on the next day (1-day group) or after 4 weeks (4-week group). Control mice received a neocortical aspiration on the same schedule as the hippocampal-lesion group. After 2 weeks of recovery, these groups received additional conditioning for 3 days. Frequency of the CR of the 1-day group was as low as spontaneous values on the first day in the post-lesion session and never reached pre-surgical level during the post-lesion sessions, while that of the control group did reach pre-surgical level during the post-lesion sessions although there was a transient decline just after lesion. In contrast to the 1-day group, the 4-week-hippocampal lesion group retained the CR and showed a further increase, without significant difference from the control group. The temporal pattern of the CR also was unchanged by the hippocampal lesion 4 weeks after learning. These results suggest a time-limited role for the hippocampus in memory retention after trace conditioning in mice: the CR acquired recently requires an intact hippocampus for its retention, but the CR acquired remotely does not. This is similar to the result reported in rabbits. Therefore, the mechanism and time course of memory consolidation after trace eyeblink conditioning may be similar in mice and rabbits.     

Comparison between Japanese and Swedish schoolchildren in regards to physical symptoms and psychiatric complaints

BACKGROUND: Physical symptoms are an increasing problem among Japanese children and adolescents, and the symptoms seem to be related to their school situation. These symptoms are prevalent in Sweden, and a comparison with Japan is of interest due to the differences in the educational system and school climate. OBJECTIVE AND METHODS: To compare physical symptoms and psychiatric complaints in school pupils from Japan and Sweden, using a questionnaire that also addressed life satisfaction and stressful life events. The study population comprised 742 Japanese children and 1,120 Swedish children attending public compulsory schools, grades 4-9 (10-15 y). Physical symptom and psychiatric complaint scores were calculated for each pupil. RESULTS: The Japanese children had significantly higher physical symptom and psychiatric complaint scores than did the Swedish children. Both the physical symptom and psychiatric complaint scores were significantly higher in adolescents than in preadolescents in Japan; this trend was less apparent in Swedish children. In addition, Japanese children were found to have considerably lower life satisfaction. Loss of appetite was the only physical symptom more prevalent in the Swedish population compared to the Japanese population.CONCLUSION: We conclude that Japanese schoolchildren have more physical symptoms and psychiatric complaints and less life satisfaction than Swedish schoolchildren of corresponding ages.     

The management of possible fishbone ingestion

OBJECTIVE: We assessed the usefulness of computed tomography (CT) in cases of suspected impaction of fish bones in the esophagus. The findings of this study were also compared with those of studies in which surgery was used to remove or confirm the presence of fish bones. We accordingly propose a management protocol to ensure optimum outcome for patients with a history of fish bone ingestion. METHODS: X-ray and CT imaging were performed in 76 patients in whom esophageal impaction of fish bones was suspected. RESULTS: Plain X-ray revealed impacted fish bones in 17 patients (22%), soft-tissue swelling but no evidence of foreign body in 5 (7%), and no abnormal findings in 54 (71%). These findings were apparent on CT scans in 31 (41%), 8 (10%), and 37 (49%), respectively. Of the 31 patients in whom CT revealed a fishbone, 17 (55%) also exhibited X-ray evidence of foreign body. Of the remainder, X-ray revealed only soft-tissue swelling in 3 (10%), and was unremarkable in 11 (35%). Among the 5 patients in whom X-ray demonstrated only soft-tissue swelling, CT was positive for foreign body in 3 (60%). Of the 54 patients in whom X-ray appearances were normal, CT revealed foreign bodies in 11 (20%) and other abnormalities in 6 (11%). CONCLUSION: In the present study, sensitivity and specificity of plain X-ray was 54.8% (17 of 31) and 100% (45 of 45), respectively. However, for CT, both sensitivity and specificity were 100%. CT was determined to be very useful in the diagnosis of impacted fish bones in the esophagus.