Effects of 2-hour nighttime nap on melatonin concentration and alertness during 12-hour simulated night work

A nighttime nap is expected to mitigate melatonin suppression during night work by blocking light input to the retina, but it is unclear. In the present study, we investigated the effects of a nap break on melatonin level, subjective sleepiness, and vigilance performance during simulated night work. Eleven healthy young males (mean ± SD age: 22.2 ± 4.1 years) participated in counterbalanced crossover design experiments with two conditions (nap vs. no nap). The subjects performed 12-hour simulated night work from 21:00 to 09:00 h (illuminance: ∼500 lx). Subjects with a nap condition took a nap for 2 hours in a dark room from 03:00, while subjects with a no nap condition continued the simulated night work. The results showed that immediately after the 2-h nap break, the melatonin level at 05:00 h temporarily recovered from light-induced melatonin suppression during the simulated night work but significantly suppressed again at 07:00 and 09:00 h. Subjective alertness and vigilance performance were impaired immediately after the nap break but subsequently enhanced. The results suggest that a single nap break for 2 hours could be a strategy to enhance alertness during the last part of night shift but inadequate for mitigating melatonin suppression.     

Recurrent paroxysmal episodes characterized by perceptual alteration in three schizophrenic patients on neuroleptic medication

Abstract A suddenly occurring episode characterized by perceptual alteration (SEPA), mainly of visual and/or auditory modalities, which repeatedly occurred in three schizophrenic patients on long-term neuroleptic medication, is described. Perceptual alteration showed some distinct features that were different from acute symptoms of schizophrenia, and was accompanied by mood changes such as severe anxiety and agitation and, in one of the patients, also by extrapyramidal symptoms. Perceptual alteration, as well as mood changes and extrapyramidal symptoms, responded well to an anticholinergic drug, biperiden. Recent studies have shown that SEPA occurred not only in schizophrenic patients but also in patients on long-term neuroleptic medication for treating other mental disorders. These findings suggest that SEPA is associated with dopaminergic hypoactivity in the brain, which is induced by long-term neuroleptic medication.     

Oestradiol Release from Self-setting Apatitic Bone Cement Responsive to Plasma-calcium Level in Ovariectomized Rats,and its Physicochemical Mechanism

The effect of plasma calcium levels on the release of oestradiol from a self-setting apatite bone cement containing 0.5% oestradiol was investigated in ovariectomized rats. The profiles of in-vitro release from the cements in simulated body fluid containing 0, 5 or 10 mg calcium per 100 mL indicated that the rate of release of oestradiol decreased with increasing calcium concentration in the dissolution media. After subcutaneous implantation of oestradiol-loaded cement in healthy and vitamin D-deficient rats, oestradiol release in diseased rats with low plasma calcium levels was significantly higher than that in healthy rats. These results suggest that in-vitro release of oestradiol from apatite bone cement was dependent on the calcium concentration in the buffer and that the in-vivo release of oestradiol from apatite bone cement was dependent on plasma calcium levels.     

Embryotoxicity of Ethanol and Acetaldehyde: Direct Effects of Mouse Embryo in Vitro

Direct embryotoxic effects of ethanol (EtOH) and acetaldehyde (AcH) on mouse embryos during early organogenesis were studied using the whole embryo culture method. Mouse embryos (Jcl-ICR) were cultured for 48 hours from day 8 & 1/2 to 10 & 1/2 (embryonic age; plug day = day 1) with EtOH- or AcH-supplemented medium. Final concentrations of EtOH ranged from 5 mM to 1 M, whereas those of AcH ranged from 0.4 μM to 400 mM. Exposure to EtOH at 500 mM or more caused early death. Growth and development in EtOH-exposed embryos were retarded as indicated by the dose-dependent decrease measured by several embryonic growth parameters. The most common EtOH-induced anomaly was exencephaly and it was observed remarkably in the 66 mM or more exposed group. Exposure to AcH at 40 μM or more caused early death. Growth and development in AcH-treated embryos were retarded as a function of dosage. The most common AcH-induced anomaly was the deformation complex of the neural tube such as transparent and prominent rhombencephalon and remarkable shortening of the posterior part of the body, with or without cyst formation. This deformation complex was observed remarkably in the 0.8 μM or more exposed group. It can be said by these results that AcH is approximately 10000 times more embryotoxic than EtOH in the early organogenetic period and both EtOH and AcH disturb the normal closure of the neural tube, but each compound affects the closure process in a different way and/or developmental stage.     

Induction of allogeneic tumour- and lymphokine-activated lymphocytes against hepatocellular carcinoma

For clinical application of adoptive immunotherapy against hepatocellular carcinoma (HCC), it is not easy to prepare tumour specific effector cells such as cytotoxic T lymphocytes (CTL). To induce potent and broad-spectrum effectors, allogeneic cultured hepatoma cell lines (JHH-4 and HuH-6) were used as stimulators of peripheral blood lymphocytes (PBL) instead of autologous HCC cells. Allogeneic tumour- and lymphokine-activated killer cells (ATLAK) were generated by a mixed culture of lymphocytes and allogeneic cultured tumour cells with recombinant interleukin-2 (rIL-2). The tumour-killing activity of ATLAK induced by HuH-6 was confirmed against HuH-6 and other different HCC cell lines (JHH-2, HuH-7 and PLC). These activated lymphocytes were significantly more potent than lymphokine-activated killer cells (LAK) in [51Cr]-releasing assay. The JHH-4 stimulated ATLAK was reactive not only with JHH-4 but also with JHH-2. The lysis of allogeneic targets could be partially inhibited by anti-CD8 and anti-CD3 but not by anti-CD4. Anti-tumour cytotoxicity in these cultures might be mediated by CD3+CD56- and CD3+CD56+ effectors. These results imply that adoptive immunotherapy for HCC with ATLAK may be more feasible than that with LAK.     

Molecular imaging of dementia

Diagnosis and treatment strategies for dementia are based on the sensitive and specific detection of the incipient neuropathological characteristics, combined with emerging treatments that counteract molecular processes in its pathogenesis. Positron emission tomography (PET) is used for diverse clinical and basic studies on dementia with a wide range of radiotracers. Approaches to visualize amyloid deposition in human brains non‐invasively with PET depend on imaging agents reacting with amyloid fibrils. The most widely used tracer is [¹¹C]‐6‐OH‐BTA‐1, also known as Pittsburgh Compound‐B, which has a high affinity to amyloid β peptide (Aβ) aggregates. Some ¹⁸F‐labeled amyloid ligands with a longer radioactive half‐life have also been developed for broader clinical applications. In addition, there have been demonstrated advantages of tracers with high specific radioactivity in the sensitive detection of amyloid, which have indicated the significance of Aβ‐N3‐pyroglutamate as a new diagnostic and therapeutic target. Furthermore, beneficial outcomes of Aβ and tau immunization in humans and mouse models have highlighted crucial roles of immunocompetent glia in the protection of neurons against amyloid toxicities. The utility of PET with a radioligand for translocator protein as a biomarker for tau‐triggered toxicity, and as a complement to amyloid and tau imaging for diagnostic assessment of tauopathies with and without Aβ pathologies, has also been demonstrated. Meanwhile, brain cholinergic function can be estimated by measuring acetylcholinesterase activity in the brain with PET and radiolabeled acetylcholine analogues. It has been reported that patients with early Parkinson's disease exhibit a reduction in acetylcholinesterase activity in the cerebral cortex, and this decline is more profound in patients with Parkinson's disease with dementia and dementia with Lewy bodies than in patients with Parkinson's disease without dementia. The Alzheimer's Disease Neuroimaging Initiative was a multicentre research project conducted over 6 years that studied changes in cognition, brain structure, and biomarkers in healthy elderly controls and subjects with mild cognitive impairment and Alzheimer's disease. An international workgroup of the National Institute on Aging‐Alzheimer's Association has suggested that Alzheimer's disease would be optimally treated before significant cognitive impairment, defined as a ‘presymptomatic’ or ‘preclinical’ stage. Therefore, PET will be of technical importance for both clinical and basic research aimed at prodromal pathologies of Alzheimer's disease.