Active clearance of human amyloid β 1–42 peptide aggregates from the rat ventricular system

A major constituent of SP in the brains of Alzheimer's disease is 39–43 amino acid peptide called β‐amyloid peptide (Aβ). Recent data have demonstrated that Aβ has a strong tendency to form insoluble aggregates and that toxic effects of Aβ is based on its aggregation. In the current study, 100 µg of human synthetic Aβ 1–42 (sAβ 1–42) was infused into the lateral ventricle of rat brain using a short‐term infusion model. At 2 or 7 days following the infusion, sAβ 1–42 was found to form insoluble aggregates, scattering throughout the entire ventricular systems. The sAβ 1–42 aggregates were partially engulfed by phagocytic cells and deposited at the meningeal vessels or the choroid plexuses. However, these deposits mostly disappeared from the ventricles by 28 days post‐infusion. Here, it is reported for the first time that considerable amounts of sAβ 1–42 are almost cleared from the rat ventricular system by the mononuclear phagocytic system.     

Scintiscanning demonstration of thymoma: Comparative study on scintiscans using201Tl,67Ga and75Se

Thymus scintigraphy was performed using²⁰¹Tl-chloride,⁶⁷-Ga-citrate and⁷⁵Se-selenomethionine on 30 thymoma patients with or without myasthenia gravis. Mass negativity was observed in 6 out of 17 (35.3 per cent) and 3 out of 13 cases (23.1 per cent), respectively. A rate of 70 per cent (21 cases out of 30) of mass positivity was observed by thymus scan using²⁰¹Tl. With regard to the relation between thymus scan and cell type,²⁰¹Tl-scan exhibited a high rate of mass positivity, regardless of the cell type while the⁷⁵Sescan showed a trend toward mass positivity in epithelial cell predominant cases. With²⁰¹Tl, mass positivity was observed when the CPM/g ratio for tumors and blood exceeded 3.0. This trend can serve as an index for the suitability of supplementary chemo- and radiotherapies, as well as for prognosis in cases of relapse, and in those for whom excision was not complete.     

Efferent and afferent innervations of Mueller's muscle related to involuntary contraction of the levator muscle: important for avoiding injury during eyelid surgery.

Because stretching of Mueller's muscle induces involuntary contraction of the levator muscle, we hypothesised that Mueller's muscle functions as a serial kind of muscle spindle of the levator muscle. To confirm the presence and location of efferent and afferent innervations of Mueller's muscle, cadavers' eyelids were microscopically and macroscopically examined, and the resultant findings were physiologically confirmed in patients' eyelids during surgery. Fine neural myelinated structures acting as a mechanoreceptor were found in the proximal Mueller's muscle. Mueller's muscle is doubly innervated by the unmyelinated sympathetic efferent nerve and the myelinated trigeminal proprioceptive afferent nerve, both of which run transversely on the proximal Mueller's muscle to join the lacrimal nerve. Electrical stimulation of the transverse nerve fibres induced involuntary contraction of both the levator muscle as the Hoffmann reflex and Mueller's muscle. Surgical injury to these nerve fibres should be avoided to preserve involuntary contraction of the levator muscle.     

The placental and mammary transport of [14C]menaquinone-4 in rats

The transfer of menaquinone-4 (vitamin K2(20] to the fetus and milk was studied in pregnant and lactating rats, respectively, after oral administration (4 mg/kg) of [3'-14C]menaquinone-4. Intestinal absorption of menaquinone-4 was rapid and the highest level of radioactivity in each tissue except guts of fetal rats was observed at 4h after dosing. The level in the fetal homogenate was low. At that time, the concentration of menaquinone-4 in the fetal liver was 84 ng/g, corresponding to 9% of the value found in the placenta. Therefore, we conclude that the transfer of menaquinone-4 to the developing rat fetus is restricted by the blood-placenta barrier, but that a sufficient amount of menaquinone-4 (more than the essential amount of vitamin K to ensure full carboxylation) can be transferred into the fetal liver. It was also observed that the radioactivity was transferred to milk after oral administration to lactating rats. Milk/blood concentration ratios at 6 and 24h after dosing were 13.8 and 65.1, respectively. The elimination half-life of radioactivity in milk was about 17h. Eighty-four percent of milk of radioactivity was due to menaquinone-4. These results suggest that the prophylactic maternal oral administration of menaquinone-4 may be efficacious for a prophylaxis of neonatal and infantile vitamin K deficiency.     

Identification of an aging-related spherical inclusion in the human brain

Inclusions, such as corpora amylacea, axonal spheroids and ubiquitin-positive granular structures, are present in aged brains. We found a phosphorylated tau-positive inclusion in brain tissues obtained from 13 non-demented subjects and five patients with Alzheimer's disease. This inclusion was spherical and 3-20 microm in size. It was most frequently detected in the hippocampal CA1 region and in the prosubiculum but was not present in the white matter. The density of this inclusion increased significantly with aging and decreased after the occurrence of neurofibrillary tangles. The presence of the inclusion was confirmed using immunoelectron microscopy. These findings show a possibility that the inclusion is a novel aging-related structure in the human brain.     

Effects of agouti-related protein,orexin and melanin-concentrating hormone on oxygen consumption in mice

Neuropeptides in the hypothalamus play a pivotal role in the regulation of energy balance. Agouti-related protein (AGRP), orexin and melanin-concentrating hormone (MCH) have been identified in the hypothalamus as orexigenic peptides. This study was undertaken to investigate the effects of AGRP, orexin and MCH on oxygen consumption. Oxygen consumption was determined by an O2/CO2 metabolism measuring system at 22 degrees C. Mice were kept unrestrained in the chamber without food or water during the light cycle, and the oxygen consumption was measured for 2 h after intra-cerebroventricular (ICV) administration. ICV administered AGRP (1 nmol/mouse) significantly decreased oxygen consumption compared to ACSF-treated controls. Orexin (1 nmol/mouse) significantly increased oxygen consumption, while MCH (1 nmol/mouse) had no significant effect compared to ACSF-treated controls. These results suggest that AGRP, orexin and MCH might have different effects on energy expenditure, thereby regulating appetite and body weight.     

Mechanical properties and osteoconductivity of porous bioactive titanium

Porous bioactive titanium implants (porosity of 40%) were produced by a plasma-spray method and subsequent chemical and thermal treatments of immersion in a 5M aqueous NaOH solution at 60 degrees C for 24 h, immersion in distilled water at 40 degrees C for 48 h, and heating to 600 degrees C for 1 h. Compression strength and bending strength were 280 MPa (0.2% offset yield strength 85.2 MPa) and 101 MPa, respectively. For in vivo analysis, bioactive and nontreated porous titanium cylinders were implanted into 6mm diameter holes in rabbit femoral condyles. The percentage of bone-implant contact (affinity index) of the bioactive implants (BGs) was significantly larger than for the nontreated implants (CGs) at all postimplantation times (13.5 versus 10.5, 16.7 versus 12.7, 17.7 versus 10.2, 19.1 versus 7.8 at 2, 4, 8 and 16 weeks, respectively). The percentage of bone area ingrowth showed a significant increase with the BGs, whereas with the CGs it appeared to decrease after 4 weeks (10.7 versus 9.9, 12.3 versus 13.1, 15.2 versus 9.8, 20.6 versus 8.7 at 2, 4, 8 and 16 weeks, respectively). These results suggest that porous bioactive titanium has sufficient mechanical properties and biocompatibility for clinical use under load-bearing conditions.     

Accumulation of imidazolone, pentosidine and N(epsilon)-(carboxymethyl)lysine in hippocampal CA4 pyramidal neurons of aged human brain

Previous studies from our laboratory demonstrated that N(epsilon)-(carboxymethyl)lysine (CML), one of the major advanced glycation end products (AGE), was accumulated in human pyramidal neurons in the hippocampus in an age-dependent manner. This suggests a potential link between AGE-accumulation and the aging process in neurons. The purpose of the present study was to examine whether this notion could be extended to other AGE structures, such as imidazolone and pentosidine. This was done using 19 human brains that were not affected by dementia. The immunohistochemical survey on distribution in brain tissues of imidazolone and pentosidine was carried out with monoclonal antibodies specific for imidazolone and pentosidine. A parallel control experiment was carried out with anti-CML antibody. The results showed that pentosidine and imidazolone were localized in neurons in different areas of human brain tissue, especially in neurons of CA4 in the hippocampus. The characteristic distribution of pentosidine and imidazolone is very similar to that of CML. Furthermore, when the accumulation of these AGE structures was compared with the age of individual brains it was found that accumulation of imidazolone, pentosidine and CML in the CA4 region increased with age. These findings taken together support the notion that the accumulation of AGE structures in the CA4 region might be closely related to the aging process in neurons.