Time estimation during nocturnal sleep in human subjects

It has been postulated that time estimation during nocturnal sleep in humans can be explained by an interval timing clock inside the brain. However, no systematic investigations have been carried out with respect to how the human brain perceives the passage of time during sleep. The brain mechanisms of over- or underestimation of time spent in sleep have not yet been clarified. Here, we carried out an experimental study in which 11 healthy volunteers participated in time estimation trials scheduled six times during 9 h nocturnal sleep periods, under carefully controlled conditions. The time estimation ratio (TER: a ratio of subjective passage of time to actual time interval) decreased significantly from the first to the sixth trial. Individual TER was positively correlated with slow wave sleep prior to the trial, while it was negatively correlated with REM sleep. Our results indicate that the human brain has an ability to estimate the passage of time during nocturnal sleep without referring to time cues, and that the accuracy of this function fluctuates from overestimation in the early hours of sleep to underestimation in the last hours of sleep.     

Sargaquinoic acid supports the survival of neuronal PC12D cells in a nerve growth factor-independent manner

Sargaquinoic acid (designated previously as MC14) was isolated from a marine brown alga Sargassum macrocarpum, and has been found to possess a novel nerve growth factor (NGF)-dependent neurite outgrowth promoting activity in PC12D cells. In this study, we explored the neuroprotective effects of MC14 in terms of its survival supporting, antioxidant and neurite-regenerating activities under NGF deficient or deprived conditions. Intriguingly, MC14 did not only promote the NGF-induced survival support on neuronal PC12D cells, but also significantly abated neuronal PC12D cell death even in the absence of NGF. The pharmacological inhibition of phosphatidylinositol-3 kinase (PI3K) by wortmannin significantly suppressed the survival supporting activity of MC14, whereas the NGF receptor (tyrosine kinase A or TrkA) inhibitor K252a showed no detectable effect on MC14 activity. These results demonstrate that MC14 supports survival of neuronal PC12D cells in an NGF-independent manner, and that PI3K may be required for the neuroprotective activity of MC14. In addition, we have shown that MC14 markedly enhanced neurite-regeneration and protected PC12D cells from hydrogen peroxide (H(2)O(2))-induced oxidative stress. These pharmacological features suggest that MC14 may be a potentially important neuroprotective agent.     

Effects of second-generation histamine H1 receptor antagonists on the sleep-wakefulness cycle in rats

The present study was performed to examine the sedative effects of second-generation histamine H(1) receptor antagonist using power spectrum analysis in the rat. Similar to ketotifen, olopatadine caused a decrease in sleep latency at a dose of 50 mg/kg, while epinastine and cetirizine showed no significant effect even at a dose of 50 mg/kg. On the other hand, no significant difference was observed in the total times of wakefulness, non-rapid eye movement sleep and rapid eye movement sleep by any drugs used in the experiments. The number of sleep phases and interval between sleep phases were also unchanged by these drugs. Ketotifen and olopatadine inhibited [(3)H]mepyramine binding to rat brain homogenates in parallel with a decrease in sleep latency. No significant effect was observed with epinastine and cetirizine on [(3)H]mepyramine binding. These findings suggest that the differences in the central nervous system (CNS) depressant effect observed in second generation H(1) receptor antagonists may be due to their liability to penetrate into the CNS.     

A chronic model for evaluating the itching associated with allergic conjunctivitis in rats

The present study was performed to develop a new model for evaluating itching associated with allergic conjunctivitis in rats. Repeated topical application of antigen caused an increase in eye scratching behavior in sensitized animals, and a significant difference was observed from days 21 to 42. Almost the same findings were observed in allergic symptoms, hyperemia and edema. Instillation of histamine also resulted in an increase in eye scratching behavior. The sensitivity to histamine in eye scratching behavior was increased by topical antigen application for 42 days after sensitization. In addition, the number of conjunctival eosinophils was significantly increased by repeated topical antigen application from days 21 to 42 in sensitized rats. Some anti-allergic drugs such as olopatadine (H1 antagonist), cetiridine (H1 antagonist) and ramatroban (thromboxane A2 (TXA2) antagonist) caused an inhibition of eye scratching behavior induced by topical sensitization in a dose-related manner. However, zafirlukast (cys-LT antagonist) caused no significant inhibition even at a dose of 30 mg/kg. The findings in present model of itching in allergic conjunctivitis were mainly through histamine H1-activity, and thromboxane A2 receptors were also involved in the response.     

C-terminal truncation of alpha-crystallin in hereditary cataractous rat lens

C-Terminal truncated alpha-crystallins have been found in lenses of hereditary cataractous rat ICR/f, including two truncated alphaB-crystallins and several truncated alphaA-crystallins. These truncated crystallins probably resulted from degradation by m-calpain and Lp82. The alphaB-crystallin with five amino acid residues deleted showed decreased chaperone activity. Compared with alpha-crystallins from the normal rat lenses, overall chaperone activity of alpha-crystallins from the mutant lenses, including the above truncated alphaB-crystallin, was remarkably reduced. The decreased chaperone activity accompanying the increase in C-terminal truncated alpha-crystallins may cause the insolubilization of many proteins in the mutant lenses, which it is likely to lead to the progression of cataract formation.     

Foveal sensitivity and fixation stability before and after macular translocation with 360-degree retinotomy

PURPOSE: To evaluate the functional changes of the fovea by scanning laser ophthalmoscopy (SLO) fundus perimetry after macular translocation with 360-degree retinotomy, and to determine whether the preoperative macular function estimated by the sensitivity of the fovea and the stability of fixation can predict visual acuity after the surgery. METHODS: Macular translocation with 360-degree retinotomy and simultaneous torsional muscle surgery were performed on 25 eyes of 25 patients with choroidal neovascularization. The index of foveal sensitivity (Isens) and the index of fixation stability (Ifix) before and after surgery were calculated from the microperimetric data. The preoperative Isens and Ifix were compared with postoperative Isens and Ifix, respectively. The correlations of preoperative Isens and Ifix with the visual acuity after the translocation surgery (VApost) were calculated. RESULTS: Isens increased in 14 (56%) of 25 eyes. Ifix improved in 10 (40%) of 25 eyes. The preoperative Isens and VApost were moderately correlated (r = 0.434, P = 0.0295), while the preoperative Ifix and VApost were highly correlated (r = - 0.530, P = 0.0057). CONCLUSION: An increase in foveal sensitivity and an improvement in the fixation stability were demonstrated quantitatively by microperimetry. The preoperative foveal sensitivity and fixation stability were correlated with the postoperative visual acuity. Microperimetry using SLO can be used to investigate foveal function before and after the translocation and to predict the postoperative visual acuity.     

Comparison of the effects of prophylactic antibiotic therapy and cost-effectiveness between cefazolin (CEZ) and Sulbactam/Ampicillin (SBT/ABPC) in gastric cancer surgery employing clinical pathway

The present study was designed to investigate the effects of prophylactic antibiotic therapy and the cost-effectiveness of Cefazolin (CEZ) and Sulbactam/Ampicillin (SBT/ABPC) in gastric cancer surgery employing clinical pathway. 157 patients (62 in the CEZ group and 95 in the SBT/ABPC group), who underwent surgery for gastric cancer at the First Department of Surgery of our hospital, were investigated. There was no significant difference between the groups with regard to sex, age, incidence of complication, stage of cancer, surgical method, operative time and blood loss, length of hospitalization, the appearance of systemic inflammatory response syndrome (SIRS), changes body temperature, white blood cell count (WBC), C-reactive protein (CRP), or clinical outcome of postoperative care by a nurse during post-operation for 7 days. The prophylactic effect of infection was also no different between the CEZ (69.4%) and SBT/ABPC (69.5%) groups. In contrast, decision analysis strongly indicated that the anticipate cost of antibiotics was higher in the latter group (yen 20402) than in the CEZ group (yen 15556), suggesting that the prophylactic effect of CEZ may be more cost-effective. Thus, evaluations of pharmacotherapy from the aspect of cost may be one of the important responsibility of hospital pharmacists in the future.     

Objective evaluation of generic drug information

Pharmacists active in health care venues need to be able to evaluate generic drugs in terms of effectiveness, safety, and economy to ensure that they are used appropriately. As part of the ongoing study of these factors, we carried out an objective evaluation of information provided for generics. A minimum of 20 commercially available products was considered for each pharmaceutical ingredient. The information subjected to evaluation consisted of the text of drug package inserts and information noted on interview forms. Using our own criteria for evaluating drug information, we attempted to quantify the amounts of information provided. Then, based on the numerical values obtained, we calculated information quantities with reference to drug prices to study the relationship between prices and available information for original drugs and their later-developed, generic equivalents. A total of 14 different pharmaceutical ingredients (327 product items) were considered, with the information quantity for generics amounting to 27.9+/-17.8-46.3+/-21.4% (Mean+/-S.D.) that for the original drugs. Examined on the basis of individual pharmaceutical companies, the corresponding ratio came to 15.1+/-7.8-62.4+/-6.4% (Mean+/-S.D.). For generics, the relationship between drug price (expressed against a value of 1.0 for original drugs) and information quantity (Qua(i)) came to 0.79+/-0.46-1.90+/-0.79% (Mean+/-S.D.). These results clearly point to the importance of evaluating information quantity for generic drugs on a maker-by-maker basis.