Decreased expression of hyaluronan synthase and loss of hyaluronan-rich cells in the anterior tibial fascia of the rat model of chemotherapy-induced peripheral neuropathy

Introduction: Previous studies on chemotherapy-induced peripheral neuropathy (CIPN) have focused on neuronal damage. Although some studies have revealed that the fascia is an important sensory organ, currently, we do not know about chemotherapy drug-induced fascial dysfunction. Objectives: This study aimed to explore the fascia as a nonneural cause of mechanical hypersensitivity in CIPN by investigating the expression of hyaluronic acid synthase (HAS) and histology of the fascia in an animal model of CIPN. Methods: Rats were intraperitoneally administered with vincristine (VCR). Mechanical hypersensitivities of the hind paw and the anterior tibial muscle were assessed. The expression of HAS mRNA in the fascia of the anterior tibial muscles was quantitated using reverse transcription polymerase chain reaction. Immunohistochemistry was also performed for HAS2, hyaluronic acid-binding protein, and S100A4 in the fascia. Results: Vincristine administration significantly decreased mechanical withdrawal thresholds in the hind paw and the anterior tibial muscle after day 3. Quantitative polymerase chain reaction showed significant downregulation of HAS mRNAs in the fascia of VCR-treated rats. Immunohistochemical analysis showed that the number of cells with strong HAS2 immunoreactivity, classified as fasciacytes by morphology and colocalized marker S100A4, decreased significantly in the VCR group. Conclusion:Hyaluronic acid plays a critical role in somatic pain sensation. Damaged fascia could be a possible cause of musculoskeletal pain in patients with CIPN. This study suggests that fascia is a nonneural cause and novel therapeutic target for chemotherapy-induced "peripheral neuropathy.

Iron and Nickel Line Diagnostics for the Galactic Center Diffuse Emission

We have observed the diffuse X-ray emission from the Galactic center (GC) using the X-ray Imaging Spectrometer (XIS) on Suzaku. The high-energy resolution and the low-background orbit provide excellent spectra of the GC diffuse X-rays (GCDX). The XIS found many emission lines in the GCDX near the energy of K-shell transitions of iron and nickel. The most pronounced features are FeI K alpha at 6.4 keV and K-shell absorption edge at 7.1 keV, which are from neutral and/or low ionization states of iron, and the K-shell lines at 6.7 keV and 6.9 keV from He-like (FeXXV K alpha) and hydrogenic (FeXXVI Ly alpha) ions of iron. In addition, K alpha lines from neutral or low ionization nickel (NiI K alpha) and He-like nickel (NiXXVII K alpha), and FeI K beta, FeXXV K beta, FeXXVI Ly beta, FeXXV K gamma and FeXXVI Ly gamma are detected for the first time. The line center energies and widths of FeXXV K alpha and FeXXVI Ly alpha favor a collisional excitation (CE) plasma for the origin of the GCDX. The electron temperature determined from the line flux ratio of FeXXV K alpha / FeXXV K beta is similar to the ionization temperature determined from that of FeXXV K alpha /FeXXVI Ly alpha. Thus it would appear that the GCDX plasma is close to ionization equilibrium. The 6.7 keV flux and temperature distribution to the galactic longitude is smooth and monotonic,in contrast to the integrated point source flux distribution. These facts support the hypothesis that the GCDX is truly diffuse emission rather than the integration of the outputs of a large number of unresolved point sources. In addition, our results demonstrate that the chemical composition of Fe in the interstellar gas near the GC is constrained to be about 3.5 times solar.Comment: 11 pages, 19 figures. Accepted for publication in PASJ Suzaku Special Issue (vol. 59 sp. 1

Anti-Malassezia-Specific IgE Antibodies Production in Japanese Patients with Head and Neck Atopic Dermatitis: Relationship between the Level of Specific IgE Antibody and the Colonization Frequency of Cutaneous Malassezia Species and Clinical Severity

Atopic dermatitis of the head and neck (HNAD) is recognized as a separate condition. Malassezia, the predominant skin microbiota fungus, is considered to exacerbate atopic dermatitis (AD), especially HNAD. In the present study, we investigated the relationships between the levels of specific IgE antibodies, colonization frequency of eight predominant Malassezia species, and clinical severity in 61 patients with HNAD (26 mild, 24 moderate, and 11 severe cases). As clinical severity increased, the levels of specific IgE antibodies against eight Malassezia species also increased. Species diversity of the Malassezia microbiota in scale samples from patients was analyzed by nested PCR using species-specific primers. The clinical severity of HNAD was correlated with the total level of specific IgE antibodies against Malassezia species and the number of Malassezia species detected

Ultraviolet B irradiation increases endothelin-1 and endothelin receptor expression in cultured human keratinocytes

AbstractThe effect of ultraviolet B (UVB) irradiation on endothelin-1 (ET-1) and ET receptor expression was examined using cultured normal human keratinocytes. Keratinocytes secreted ET-1 in the medium at a level of 2.1 pg/day/105 cells. UVB irradiation up to 10 mJ/cm2 increased ET-1 secretion 3-fold, and potentiated expression of mRNA for ET-1. Both ETA and ETB receptor mRNAs were detected in keratinocytes, and their expression was up-regulated by 5 mJ/cm2 UVB irradiation

Synthesis, Crystal Structures, Electronic Spectra, and Magnetic Properties of Thiolato-Bridged Trinuclear Cobalt(II) Complexes with N, N, S-Tridentate Thiolate Ligands

New trinuclear CoII complexes, [{Co(apaet)2}2Co]X2 (apaet– = 2-[(3-aminopropyl)amino]ethanethiolato; X = SCN (1), ClO4 (2), NO3 (3), Cl (4), Br (5), I (6)) and [{Co(apampt)2}2Co]X2 (apampt– = 1-[(3-aminopropyl)amino]-2-methylpropane-2-thiolato; X = NO3(7), ClO4 (8), Cl (9), Br (10), I (11)), and mononuclear CoIII complexes, [Co(apaet)2]X (X = ClO4 (12), NO3 (13)), were synthesized. Single-crystal X-ray crystallography of 1 and 7 confirmed that the trinuclear complexes have a linear arrangement of octahedral CoIIS2N4-tetrahedral CoIIS4-octahedral CoIIS2N4 chromophores where two thiolate ligands are coordinated to each terminal Co atom in a mer coordination mode and the two thiolato S atoms are further bound to the central Co atom, which is consistent with the electronic spectra and antiferromagnetic propertie

Intrathecal Administration of the α1 Adrenergic Antagonist Phentolamine Upregulates Spinal GLT-1 and Improves Mirror Image Pain in SNI Model Rats

Mirror image pain (MIP) is a type of extraterritorial pain that results in contralateral pain or allodynia. Glutamate transporter-1 (GLT-1) is expressed in astrocytes and plays a role in maintaining low glutamate levels in the synaptic cleft. Previous studies have shown that GLT-1 dysfunction induces neuropathic pain. Our previous study revealed bilateral GLT-1 downregulation in the spinal cord of a spared nerve injury (SNI) rat. We hypothesized that spinal GLT-1 is involved in the mechanism of MIP. We also previously demonstrated noradrenergic GLT-1 regulation. Therefore, this study aimed to investigate the effect of an α1 adrenergic antagonist on the development of MIP. Rats were subjected to SNI. Changes in pain behavior and GLT-1 protein levels in the SNI rat spinal cords were then examined by intrathecal administration of the α1 adrenergic antagonist phentolamine, followed by von Frey test and western blotting. SNI resulted in the development of MIP and bilateral downregulation of GLT-1 protein in the rat spinal cord. Intrathecal phentolamine increased contralateral GLT-1 protein levels and partially ameliorated the 50% paw withdrawal threshold in the contralateral hind paw. Spinal GLT-1 upregulation by intrathecal phentolamine ameliorates MIP. GLT-1 plays a role in the development of MIPs