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X-ray absorption fine structure (XAFS) spectra, especially X-ray absorption near-edge structure (XANES), show unique features depending on the chemical states and structures in the vicinity of the X-ray absorbing elements. As such, they can be used to identify the chemical environment of elements. XAFS spectroscopy was applied to investigate the chemical environment of chloride ions in a metastable form A crystal of the antibiotic clarithromycin hydrochloride hydrate. The XANES of the form A crystals showed low similarity to that of the active pharmaceutical ingredient (API) hydrochloride salt crystals, but showed a high similarity to that of a hydrochloride aqueous solution. This indicated that the chloride ion in the form A crystals predominantly interacted with water molecules and was fully hydrated, which was consistent with the previous presumption that form A may be high water-content crystals. This study demonstrated that this XAFS spectroscopy method would be a potent alternative technique for evaluating APIs., (Copyright © 2020 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

The involvement of N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)/kainate (KA) receptors in the induction of c-Fos and Zif/268 expression in spinal dorsal horn neurons following noxious thermal or mechanical stimulation, or formalin injection into the rat hind paw was examined by intrathecal administration of a competitive NMDA receptor antagonist, 2-amino-5-phosphonopentanoic acid (APV) or an AMPA/KA receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), or both, 30 min prior to noxious stimulation. APV caused a significant reduction in the level of c-Fos expression in the superficial layer induced by each of these three noxious stimuli. The effects of APV on Zif/268 expression or of CNQX on c-Fos or Zif/268 expression in the superficial layer induced by these three noxious stimuli were dependent on the type of stimulus applied to the rat hind paw. The noxious thermal stimulus-evoked c-Fos expression level was reduced by APV and/or CNQX, while Zif/268 expression was hardly changed. Both c-Fos and Zif/268 expressions following formalin injection were reduced by APV alone and APV+CNQX, but not by CNQX alone. Zif/268 expression following noxious mechanical stimulation was significantly reduced only by APV+CNQX although APV or CNQX alone did not affect the expression, while c-Fos expression was reduced by APV and APV+CNQX but not by CNQX alone. These findings suggest that NMDA and AMPA/KA receptors are differentially involved in c-Fos and Zif/268 expression in the spinal dorsal horn following noxious thermal, formalin and mechanical stimulation., (Copyright 2002 Elsevier Science Ireland Ltd. and the Japan Neuroscience Society.)

A cephalometric study was conducted on 12 patients with repaired cleft palate to evaluate the stability in level and length of the base attachment of the velopharyngeal complex following pharyngeal flap surgery by a modified velopharyngoplasty. Complete velopharyngeal closure and normal articulation with a speech appliance were confirmed in all patients prior to pharyngeal flap surgery, which was performed on patients 10 years of age and above. Cephalometric radiographs were taken immediately, 1 year, 2 years and 3 years postoperatively. Cephalometric analysis revealed that although the level and length of the base of the velopharyngeal complex showed changes during the first postoperative year, they remained stable when compared with the palatal plane during the last two years. This indicated therefore that the base of a velopharyngoplasty should be attached at the same level of the palatal plane, namely the level of velopharyngeal closure, and that the procedure appeared useful in producing a stable velopharyngeal complex.

To clarify the characteristics of growth of the nasopharynx, comparison of the cephalometric growth of bones surrounding nasopharynx between 61 patients with complete unilateral cleft lip and palate (UCLP group) and 82 non-cleft controls (NCC group) was carried out. All of the subjects were divided into four developmental stages (i.e. stage 1 at 4 years of age, stage 2 at 8 years of age, stage 3 at 12 years of age and stage 4 at 17 years of age). Measurements on the antero-posterior and the vertical dimensions were derived from a coordinate system and points on bones surrounding the nasopharynx on lateral X-ray cephalograms, and results were analyzed by multivariate analysis and t-test. The results showed that (a) the posterior maxillary point (PMP) in the UCLP group was located more postero-superiorly than that in the NCC group, and this was the main factor that allows discrimination between the two groups and (b) the cranial base, posterior maxilla and the cervical vertebrae were found to be in independent in growth, however, the nasopharyngeal triangle connecting three points on these three bones (Ho: cranial base; PMP: posterior maxillary point; At: atlas) showed harmonious growth in both the UCLP and NCC groups.

A novel nucleotide change in the collagen X gene was identified in a Japanese family with Schmid metaphyseal chondrodysplasia (SMCD). The T to C change at nucleotide 1951 resulted in replacement of tryptophan by arginine at residue 651 (W651R). This missense mutation is considered to be responsible for SMCD because 1, the same mutation was not be identified in the collagen X gene from normal individuals; 2, the mutation segregated with the SMCD phenotype in the index family; 3, the substituted amino acid is highly conserved in type X collagens, and 4, the mutation causes a marked change in the hydrophobicity profile of the surrounding region in the NC1 domain. This novel mutation (W651) seems to have the same impact on bone development as W651X mutation.

We report here the cloning and expression of a rat full-length cDNA encoding preproendothelin-3 (preproET-3). The predicted rat preproET-3 consisted of 167 amino acid residues. As in other ET-family peptides, the mature rat ET-3 was predicted to be produced through unusual processing from a 41-residue intermediate, the big ET-3 in rat. Transient transfection of COS-7 cells with the cloned preproET-3 cDNA resulted in the production of mature ET-3 and this production was inhibited by phosphoramidon, a metaloprotease inhibitor. This suggested that a phosphoramidon sensitive mechanism was involved in the production of ET-3 in the transfected COS-7 cells. Northern blot analysis showed that an approximately 3.0-kb rat preproET-3 mRNA was expressed in rat tissues, including the eye ball, submandibular gland, brain, kidney, jejunum, stomach and spleen. A 2.0-kb and a 3.3-kb mRNA were also detected in the eye ball and small intestine, respectively. The distinct distribution of rat preproET-3 mRNA from that of preproET-1 mRNA suggested that ET-1 and ET-3 played different roles.