Yukari Gono

IMMUNOHISTOCHEMICAL LOCALISATION OF REGULATORY NEUROPEPTIDES IN HUMAN CIRCUMVALLATE PAPILLAE

The occurrence and distribution of neuropeptide‐containing nerve fibres in the human circumvallate papillae were examined by the peroxidase–antiperoxidase immunolocalisation method using surgical specimens that had not been subjected to radiotherapy, and the abundance of neuropeptide‐containing fibres was expressed as the percentage of total nerve fibres demonstrated by protein gene product (PGP) 9.5 immunoreactivity for a quantitative representation of these peptidergic fibres. Substance P (SP) and calcitonin gene‐related peptide (CGRP) immunoreactive (IR) nerve fibres were densely distributed in the connective tissue core of the circumvallate papillae, and some SP and CGRP‐IR fibres were associated with the taste buds. A moderate number of vasoactive intestinal polypeptide (VIP)‐IR fibres and a few galanin (GAL)‐IR fibres were also seen in the connective tissue core and subepithelial layer. There were, however, no VIP‐IR or GAL‐IR fibres associated with the taste buds. Neuropeptide Y (NPY)‐IR fibres were few and were associated with the blood vessels. Within the epithelium of the circumvallate papillae, no peptidergic fibres were found, although a number of PGP 9.5‐IR fibres were detected. The abundance of SP, CGRP, VIP, and GAL‐IR fibres expressed as the percentage of total PGP 9.5 IR fibres was 25.35±3.45%, 22.18±3.26%, 10.23±1.18%, and 4.12±1.05%, respectively. The percentage of NPY‐IR fibres was below 3%. In a deeper layer of the papillae, a few VIP, GAL, and NPY‐IR ganglion cells were found, and VIP immunoreactivity was detected in a few cells of the taste buds. There was no somatostatin, leucine enkephalin, or methionine enkephalin immunoreactivity in the circumvallate papillae. These results suggest that the dense SP and CGRP‐IR fibres within the connective tissue core of the human circumvallate papillae may be involved in the deep sensation of the tongue.

Hypoxic adaptation of the peptidergic innervation in the rat carotid body

The abundance of substance P (SP)-, calcitonin gene-related peptide (CGRP)-, vasoactive intestinal polypeptide (VIP)-, and neuropeptide Y (NPY)-immunoreactive nerve fibers in the carotid body was compared between normoxic and chronically hypoxic rats (10% O2 and 3.0-4.0% CO2 for 3 months). The immunoreactive fibers appeared as thin processes with many varicosities, and were distributed mainly around the vasculatures. In the normoxic control carotid body, NPY fibers were more numerous than VIP, CGRP, and SP fibers. In the chronically hypoxic rats, the carotid body was enlarged several fold, and the mean absolute number of VIP and NPY fibers was 3.88 and 2.22 times higher than in the normoxic carotid body, respectively, although that of SP and CGRP fibers was not changed. When expressed as density per unit area of the parenchyma, the density of SP and CGRP fibers in the chronically hypoxic carotid body decreased significantly to under 50%, the density of VIP fibers increased significantly 1.80 times, and the density of NPY fibers were unchanged. Immunoreactivity for four neuropeptides was not found in the glomus cells of normoxic or chronically hypoxic carotid bodies. These results suggest that altered peptidergic innervation of the chronically hypoxic carotid body is one feature of hypoxic adaptation. Because these neuropeptides are vasoactive in nature, altered carotid body circulation may contribute to modulation of the chemosensory mechanisms by chronic hypoxia.

The efficacy of goshuyuto, a typical Kampo (Japanese herbal medicine) formula, in preventing episodes of headache.

ABSTRACT Objective: The purpose of this clinical trial was to assess the efficacy of goshuyuto, a typical Kampo formula, in preventing episodes of headache in chronic headache patients. Research design and methods: Because the treatment target of a Kampo formula is decided on a basis different to that of Western medicine, we first selected patients belonging to a subgroup that responded to goshuyuto before conducting the usual randomized controlled trial. During stage 1, the subjects were instructed to orally consume goshuyuto for 4 weeks. Only those subjects judged as responders advanced to stage 2, during which a double-blind, randomized, placebo-controlled study was conducted. The subjects consumed the same dose of goshuyuto or placebo for 12 weeks. Results: Of the 91 subjects enrolled in stage 1, 60 were judged as responders. Of these, 53 advanced to stage 2; 28 were assigned to the goshuyuto group and 25 to the placebo group. The decrease in the number of days on which headache episodes occurred was greater in the goshuyuto group than in the placebo group (2.6 ± 3.7 vs. 0.3 ± 4.0 days, p = 0.034); no difference was observed with regard to the reduction in the frequency of consuming reliever medications (2.2 ± 4.0 vs. 1.4 ± 8.2, p = 0.672). Improvement in the associated symptoms was observed in more than 50% of the subjects in the goshuyuto group. Conclusion: Goshuyuto is useful in preventing episodes of headache in chronic headache patients. Responder-limited design is a candidate for evaluating Kampo medicine.

Transient appearance of substance P-like immunoreactivity in the granular convoluted tubules of the male mouse submandibular gland: light- and electron-microscopic studies

Abstract The time of appearance and distribution of substance P (SP)-like immunoreactivity in the granular convoluted tubule cells of the developing male mouse submandibular glands were examined, and the subcellular localization of SP-like immunoreactivity was investiagted by electron microscopy. At 25 days of age, SP-like immunoreactivity was first detected in the supranuclear cytoplasm of the granular convoluted tubule cells, which occurred either singly or in small clusters. At 30 and 35 days of age, granular convoluted tubule cells with SP-like immunoreactivity were more numerous than in the earlier stages, as the volume ratio of the cells increased. Not all granular convoluted tubule cells demonstrated SP-like immunoreactivity. The number of cells with SP-like immunoreactivity decreased at 60 days of age, and these cells had completely disappeared at 90 days of age. Most, but not all, secretory granules in the granular convoluted tubule cells were strongly labeled with gold particles, indicating that the subcellular site of SP-like substance is in the secretory granules within the cells. The findings suggest that the physiological role of the SP-like substance secreted from the GCT cells is restricted to the early postnatal stages, and that it may be involved in the development of the oral mucosa or digestive tract as a trophic factor.