Cathepsin K inhibitor causes changes in crystallinity and crystal structure of newly-formed mandibular bone in rats

Cathepsin K inhibitors are new drugs with the potential for the treatment of osteoporosis because they sustain bony remodelling better than bone resorption inhibitors such as bisphosphonates. The treatment of osteoporosis with inhibitors of bony resorption is associated with osteonecrosis of the jaw, as the deterioration in bony quality that they induce is thought to be one of its causes. The quality of bone is delineated by structural and material characteristics (which include the degree and quality of mineralisation, and depends on the content of proteoglycan and the structural integrity of the bony collagen).^1,2 Animal and clinical studies have shown that cathepsin K inhibitors improve the mineral density and structural characteristics of bone, but their effect on the rest remains unknown. We therefore hypothesised that these inhibitors will affect the material characteristics of newly-formed mandibular bone. To verify our hypothesis, we used Raman microspectroscopy to examine such bone in rats that were given a cathepsin K inhibitor, and found unusual crystallinity and an increased substitution of carbonate (CO₃^2?) in its crystal structure.     

Cellular localization of the diazepam binding inhibitor (DBI) in the gastrointestinal tract of mice and its coexistence with the fatty acid binding protein (FABP).

The diazepam binding inhibitor (DBI), initially isolated as an endogenous 10-kDa polypeptide from the brain, has the ability to displace ligands from benzodiazepine binding sites on gamma-aminobutyric acid (GABA) receptors. However, DBI is widely distributed outside the brain, with the highest expression in the intestine. The present in situ hybridization study revealed the cellular expression of DBI mRNA throughout the gastrointestinal tract of mice, showing it to be intensely expressed in the spinous layer in the stratified squamous epithelium of the oral cavity, esophagus and forestomach, in surface mucous cells in the glandular stomach, and in columnar (absorptive) cells of the intestinal villi. A precise identification of DBI-expressing cell types was confirmed immunohistochemically, although the expressing cells detectable by the two histochemical methods differed slightly in their extension. Noteworthily, DBI always coexisted with the fatty acid binding protein (FABP), which participates in the uptake and metabolic processing of long chain fatty acids. In addition to the biochemical finding that DBI is identical with the acyl-CoA binding protein (ACBP), the distributional patterns of DBI and its colocalization with FABPs suggests its involvement in the absorption and metabolism of lipid in the epithelia of the digestive tract.     

Brain strategies for reading in the second language are determined by the first language

Brain activation associated with reading was investigated in ten normal Japanese volunteers (five highly literate in both Japanese and English) and ten American native English speakers (five highly literate in both English and Japanese) in order to determine the neuroanatomic substrates employed in reading the first language (L1), and to determine the effect of L1 on the neurosubstrates involved in reading the second language (L2). The study was performed using blood oxygenation level dependent (BOLD) contrast functional magnetic resonance imaging (fMRI) on a high-field (3.0T) system specifically optimized for fMRI. The activation patterns in Japanese subjects reading Japanese (L1) were substantially different from the patterns obtained in American subjects reading English text (L1). The activation patterns reading L2 were virtually identical to the patterns seen when reading L1 in both Japanese and English natives highly literate in both language systems. The results demonstrated that the neuroanatomical substrates underlying the cognitive processing of reading are differentially determined based on the language system. The study further indicates that the cognitive processes for reading in the second language involve the same cortical structures employed for the first language, supporting the hypothesis that the second language represents the cognitive extension of the first language.     

The temperature-dependent modulation of an inhibitory circuit in hippocampal slices as revealed by a population spike recording is mediated by extracellular adenosine.

We examined the effects of temperature on excitatory synaptic transmission and the recurrent inhibitory loop in CA1 neurons in guinea pig hippocampal slices. Increasing the temperature of the perfusing medium from 30 to 49 degrees C resulted in attenuation of both the amplitude of the synaptically evoked CA1 population spikes and the paired-pulse inhibition (PPI) of the spikes. A bath application of 2 microM picrotoxin, a gamma-aminobutyric acid receptor antagonist, did not affect the amplitude of the CA1 population spikes, but it significantly reduced PPI during the early heating phase (30-32 degrees C). In contrast, the application of 1 mM theophylline or 50 microM 8-phenyltheophylline, a selective adenosine A1 receptor antagonist, resulted in significant augmentation of the PPI during the early phase of hyperthermia (30-34 degrees C) and a significant increase in the amplitude of the CA1 population spikes at higher temperatures (34-43 degrees C). These results suggest that increased activation of adenosine A1 receptors in response to a temperature increase depresses not only excitatory synaptic responses, but also the strength of the inhibitory circuit in CA1 neurons. Furthermore, hyperexcitability of CA1 pyramidal neurons was seen in the middle of the heating range (34-38 degrees C), excitatory responses still being present, but the strength of the inhibitory circuit significantly reduced.     

Carcinogenicity examination of betel quid. II. Effect of vitamin a deficiency on rats fed semipurified diet containing betel nut and calcium hydroxide

The effect of vitamin A deficiency on the carcinogenicity of betel quid was studied, using long‐term feeding of vitamin‐A‐deficient and ‐sufficient diets with and without betel nut and calcium hydroxide in ACI rats. A high incidence of focal epithelial hyperplasia was observed in the upper digestive tract (tongue, buccal oral mucosa, esophagus, and forestomach) of rats in the group given the vitamin‐A‐deficient diet mixed with betel nut and calcium hydroxide. The vitamin‐A‐deficient group also showed a high incidence of squamous papilloma in the tongue, buccal mucosa, and forestomach. The incidence of hyperplastic lesions of the tongue and buccal oral mucosa was significantly higher in this group than in the group receiving the vitamin‐A‐sufficient diet with betel nut and calcium hydroxide. These results suggest that the vitamin‐A‐deficient condition enhanced the growth of epithelial hyperplasia that was due to the administration of the betel quid ingredients. However, vitamin A did not protect against the development of altered liver cell foci, which were frequently seen with a small number of hepatocellular neoplasms in all groups given the diets containing betel nut and calcium hydroxide (both vitamin‐A‐deficient and ‐sufficient groups).     

Dissociation of body-centered and stimulus-centered representations in unilateral neglect.

BACKGROUND: Previous studies on unilateral neglect have shown that there are at least two types of neglect-i.e., body-centered and stimulus-centered neglect. These symptoms suggest that the human brain has at least two different reference frames for processing external space. It is unknown, however, whether these two frames are represented independently in the brain and if so, which areas (or networks) of the brain are responsible for each frame of reference. OBJECTIVE: To determine whether body-centered neglect and stimulus-centered neglect can be dissociated in patients with brain injury. METHODS: New figure discriminative cancellation tasks were designed to simultaneously assess body-centered neglect and stimulus-centered neglect. Two neglect patients with lesions located in different anatomic regions were required to circle every complete figure and to cross out every figure with a missing portion on a sheet of white (29.7 x 42 cm) paper. RESULTS: Patient 1 omitted leftward stimuli on the paper, but the stimuli he found were correctly circled or crossed out. On the other hand, Patient 2 marked stimuli across the paper although he mistakenly circled stimuli that were missing a portion of their left side. Neither patient manifested interaction between the two types of neglect. CONCLUSION: The results of this study clearly showed double dissociation between the two types of neglect. Furthermore, it not only provides evidence that there are two distinct systems of reference frame for external space in the human brain, but also adds new knowledge indicating that these two systems function independently, at least in part.