Cerebral perfusion changes in chronic dizziness: A single-photon emission computed tomography study.

BACKGROUND AND PURPOSE: Dizziness may persist even after the causative vestibular imbalance subsides. Although the precise mechanism of chronic dizziness is unknown, various cerebral activity changes associated with it have been reported. To understand its mechanism in the absence of the causative vestibular imbalance, we compared cerebral changes in chronic dizziness with and without persistent vestibular imbalance. METHODS: Between September 2014 and March 2020, we examined regional cerebral blood flow (rCBF) in 12 patients having chronic post-lateral medullary infarction dizziness with persistent brainstem vestibular imbalance and 23 patients having chronic dizziness without currently active vestibular imbalance using single-photon emission computed tomography (SPECT) with 99m Technetium-ethyl cysteinate dimer. Further, we analyzed the SPECT images using a voxel-based group comparison. RESULTS: We observed a decreased rCBF in the occipital lobe and increased rCBF in the medial and inferior parts of the temporal lobe in patients having chronic dizziness with and without active vestibular imbalance compared to healthy controls. However, only patients having chronic dizziness without active vestibular imbalance exhibited increased rCBF in the frontal lobe, including the orbitofrontal cortex. CONCLUSION: This is the first study to highlight the difference in rCBF changes between patients having chronic dizziness with and without active vestibular imbalance. Decreased occipital lobe activity and increased medial and inferior temporal lobe activity may be related to keeping dizziness perception triggered regardless of the presence or absence of active vestibular imbalance, whereas increased frontal lobe activity may explain the dizziness background to persist after the disappearance of vestibular imbalance.

Development of an Animal Model of Onychomycosis in Guinea Pigs.

Onychomycosis is a common and intractable superficial mycosis that occurs worldwide. Treatment with both oral and topical drugs is recommended, but the objective evaluation procedure to determine the efficacy of and the appropriate delivery system for the drugs remains controversial. This may be attributed to the lack of a reliable animal model that not only mirrors the pathophysiology of human onychomycosis but is also feasible. Therefore, we attempted to establish an animal model of onychomycosis using immunosuppressed guinea pigs and elucidate the pathophysiology of human onychomycosis. In the present study, we applied Trichophyton mentagrophytes TIMM2789 to the hind limb nails of corticosteroid-treated guinea pigs. The nails were examined macroscopically and histopathologically at 0, 14, and 42 days after a 2-week exposure period to the fungus. A large portion of the experimentally infected nails showed discoloration, which is an important clinical sign, and most infections were confirmed histopathologically in the deep layer of the nail plate at all time points. The infection rates at 0, 14, and 42 days after exposure were 39%, 61%, and 78%, respectively. Thus, we established an animal model of onychomycosis with good reproducibility and that might be appropriate for extrapolation to the pathophysiology of the human disease.

Cellular uptake properties of lamotrigine in human placental cell lines: Investigation of involvement of organic cation transporters (SLC22A1-5).

Lamotrigine (LTG) is an important antiepileptic drug for the treatment of seizures in pregnant women with epilepsy. However, it is not known if the transport of LTG into placental cells occurs via a carrier-mediated pathway. The aim of this study was to investigate the uptake properties of LTG into placental cell lines (BeWo and JEG-3), and to determine the involvement of organic cation transporters (OCTs, SLC22A1-3) and organic cation/carnitine transporter (OCTNs, SLC22A4-5) in the uptake process. The uptake of LTG at 37 °C was higher than that at 4 °C. OCT1 and OCTNs were detected in both cell lines. The uptake of LTG was not greatly affected by the extracellular pH, Na+-free conditions, or the presence of l-carnitine, suggesting that OCTNs were not involved. Although several potent inhibitors of OCTs (chloroquine, imipramine, quinidine, and verapamil) inhibited LTG uptake, other typical inhibitors had no effect. In addition, siRNA targeted to OCT1 had no significant effect on LTG uptake. The mRNA expression in human term placenta followed the order OCTN2 > OCT3 > OCTN1 > OCT1 ≈ OCT2. These observations suggested that LTG uptake into placental cells was carrier-mediated, but that OCTs and OCTNs were not responsible for the placental transport process.

[Antifungal Activity of Luliconazole Nail Solution on in vitro and in vivo Onychomycosis Model].

We evaluated luliconazole nail solution, originally generated formulation, for the topical treatment of onychomycosis by two infection models. First, a suspension of Trichophyton mentagrophytes was dropped onto the ventral layer of human nail plate and these nails were set in Franz diffusion cells. After 9-day culture, luliconazole nail solutions (1, 3, and 5%) were applied to the dorsal surface of the nails once a day for 7 days. After application, fungal viability was assessed by measuring the ATP contents of the samples. The dose-dependent efficacy was confirmed, with 3% and 5% luliconazole nail solutions producing significantly lower ATP levels at 7-day treatment. When 3% and 5% luliconazole nail solutions were evaluated in a rabbit model of onychomycosis, both concentrations completely inhibited the recovery of fungi on culture after 4-week treatment. We therefore think these results indicate that 5% luliconazole nail solution is sufficiently potent for treatment of onychomycosis.

[Effect of high mobility group box 1 (HMGB1) in cultured human periodontal ligament cells].

The periodontal ligament (PDL) is a fibrous connective tissue that exists in the cementum and the alveolar bone. Periodontitis is a chronic inflammatory disease that is caused by a bacterial infection in the periodontal region. This infection increases the production of inflammatory cytokines and causes the destruction of periodontal tissue. High mobility group box 1 (HMGB1) is a nuclear nonhiston DNA-binding protein that is present in many eukaryotic cells. HMGB1 is released actively from macrophages and monocytes stimulated by lipopolysaccharide or tumor necrosis factor-alpha and passively from damaged cells and necrotic cells. Extracellular HMGB1 signals through a specialized receptor for advanced glycation end products (RAGE), toll-like receptor 2 (TLR2), and toll-like receptor 4 (TLR4). According to a recent report, HMGB1 is of concern in periodontitis. The purpose of this study was to examine the effect of HMGB1 in PDL cells. To investigate RAGE, TLR2 and TLR4 mRNA in PDL cells, reverse transcript-polymerase chain reaction experiments were performed. PDL cells were stimulated with HMGB1, with or without anti-RAGE, TLR2 and TLR4 antibodies. IL-6 and IL-11 production was measured using an enzyme-linked immunosorbent assay, and mRNA expression was quantified by real-time PCR. PDL cells expressed RAGE, TLR2 and TLR4 mRNA. Production and mRNA expression of IL-6 and IL-11 were augmented in PDL cells stimulated with HMGB1. In addition, they were also suppressed by anti-RAGE, TLR2 and TLR4 antibodies. In conclusion, PDL cells produce IL-6 and IL-11 in response to HMGB1 via RAGE, TLR2 and TLR4.