Effect of Physiological Changes in the Skin on Systemic Absorption of Tacrolimus Following Topical Application in Rats.

Tacrolimus (TL) ointment is a topical treatment for atopic dermatitis, a disease that exhibits various skin conditions. The effect of skin pathologies on the systemic absorption of TL and related side effects remains unknown. This study aimed to investigate factors affecting the cutaneous absorption of TL. We prepared various skin models in hairless rats by tape stripping, injection of prophlogistic material solution (PMS), and continuous subcutaneous adrenaline (Adr) infusion. In vivo absorption studies were conducted, with measurements of transepidermal water loss (TEWL) and skin blood flow as physiological parameters. Very little TL absorption was observed through intact skin. Greater TL absorption was noted in skins with high TEWL values and fully stripped skin with PMS injections. In contrast, Adr infusion, which reduced skin blood flow, resulted in decreased TL absorption through fully stripped skin. Combined use of TL and Adr on skin with PMS injections resulted in suppression of TL absorption. Our results revealed that TL absorption following topical application is affected by alterations in the skin barrier, blood flow, and vascular permeability. We propose an administration plan for TL in a flowchart as a means of preventing systemic side effects.

Effect of ultrasound treatment of the skin on activation of Langerhans cells and antibody production in rodents.

In this study, we investigated whether stimulating the skin with ultrasound (US) could activate Langerhans cells (LCs) - antigen-presenting cells in the epidermis and stimulate antibody production following the subcutaneous and intradermal injection of ovalbumin (OVA) in hairless rats and BALB/c mice. Three different US frequencies (20 kHz, 1, and 3 MHz) were used and the expression of langerin was monitored as a marker for the activation of LCs in the epidermal sheet. In hairless rats, the langerin signal peaked at 12 h post-US treatment and returned to control levels at 24 h. Its expression increased with increasing irradiation time, up to 20 min, and 20 kHz US induced the highest langerin expression among the three frequencies tested. These results were reproduced in BALB/c mice. When the skin was pretreated with 20 kHz US at 0.41 W/cm2 for 10 min, the production of OVA-specific immunoglobulin G1 in mice increased by 2.8- and 3.4-fold 28 days after subcutaneous or intradermal OVA injections, respectively. These findings indicate that stimulating the skin with US can trigger skin immune responses, leading to effective antigen-specific antibody production. US-assisted transdermal vaccine delivery delivers antigens to the skin and evokes an immune response, providing an effective noninvasive immunization strategy.

Effects of self-locomotion on the activity of place cells in the hippocampus of a freely behaving monkey.

The activity of hippocampal cell assemblies is considered to function as the neural substrate for a cognitive map in various animal species. The firing rate of hippocampal place cells increases when an individual animal reaches a specific location in an environment. Although cumulative views on place cells have been revealed by studies using rodents under free-behavior conditions, few studies have addressed the spatial representation provided by hippocampal neurons in primates. Moreover, although previous work in rats has demonstrated the importance of locomotion velocity and direction in the spatially selective discharge of hippocampal neurons, it remains unknown whether a corresponding phenomenon exists in the primate hippocampus. In the present study, we recorded the activity and investigated the spatial representation of the hippocampal neurons in a freely behaving monkey performing a shuttle-movement task. We observed increased activity in a subset of hippocampal neurons (place cells) when the monkey crossed a particular location. Many of the monkey place cells exhibited sensitivity to locomotion velocity rather than to locomotion direction. These results suggest the existence of primate hippocampal place cells comparable to those in rodents, with the exception that, in primates, velocity information has a stronger impact on place cell activity than directional information.

Data on the activity of place cells in the hippocampal CA1 subfield of a monkey performing a shuttling task.

This data article provides spike-timestamps of place cells recorded in a male Japanese monkey and the animal's sequential positions during the performance of a shuttling task on a rectangular track. All data were recorded in the right hippocampal CA1 subfield, while the monkey performed the task under a freely behaving condition. These were the source data on the monkey place cells in our related research article entitled "Effects of self-locomotion on the activity of place cells in the hippocampus of a freely behaving monkey" [1]. In addition, here we show a movement directional activity of a place cell in two-dimensional space as an example of data utilization. The source data are freely accessible [2] and can be used by other researchers to obtain new insights into place cells, such as functional differences between animal species.