Development and Characterization of a Novel FVB-PrkdcR2140C Mouse Model for Adriamycin-Induced Nephropathy.

The Adriamycin (ADR) nephropathy model, which induces podocyte injury, is limited to certain mouse strains due to genetic susceptibilities, such as the PrkdcR2140C polymorphism. The FVB/N strain without the R2140C mutation resists ADR nephropathy. Meanwhile, a detailed analysis of the progression of ADR nephropathy in the FVB/N strain has yet to be conducted. Our research aimed to create a novel mouse model, the FVB-PrkdcR2140C, by introducing PrkdcR2140C into the FVB/NJcl (FVB) strain. Our study showed that FVB-PrkdcR2140C mice developed severe renal damage when exposed to ADR, as evidenced by significant albuminuria and tubular injury, exceeding the levels observed in C57BL/6J (B6)-PrkdcR2140C. This indicates that the FVB/N genetic background, in combination with the R2140C mutation, strongly predisposes mice to ADR nephropathy, highlighting the influence of genetic background on disease susceptibility. Using RNA sequencing and subsequent analysis, we identified several genes whose expression is altered in response to ADR nephropathy. In particular, Mmp7, Mmp10, and Mmp12 were highlighted for their differential expression between strains and their potential role in influencing the severity of kidney damage. Further genetic analysis should lead to identifying ADR nephropathy modifier gene(s), aiding in early diagnosis and providing novel approaches to kidney disease treatment and prevention.

Assessment of thiamylal sodium as a euthanasia drug in mice.

Euthanasia agents should rapidly induce death and loss of consciousness without causing pain or distress. Various methods exist for the euthanasia of laboratory animals, and injectable anesthetics, particularly barbiturate derivatives, are widely used due to the rapid onset of unconsciousness induced by these agents. Moreover, pharmaceutical-grade drugs should be used to eliminate undesirable side effects as much as possible. However, in Japan, the sale of pharmaceutical-grade pentobarbital sodium (PB) ended in 2019, and that of secobarbital sodium (SB) ended in 2023, leading to a demand for new pharmaceutical-grade injectable euthanasia drugs. This study evaluates thiamylal sodium (TM), a barbiturate derivative that is available domestically, as a euthanasia agent for mice. The results showed that when administered at dosages of 200 mg/kg or more, TM exhibited effects equivalent to those of PB and SB. In addition, the impact of TM administration on hematological characteristics was examined. In female mice administered TM, decreased blood chloride and calcium levels and increased aspartate aminotransferase and alanine aminotransferase levels, which are markers of liver damage, were observed. These findings suggest that high concentrations of TM may affect renal and liver function. This study revealed that TM is effective as a euthanasia agent at dosages of 200 mg/kg or more. However, considering the potential risks of renal and liver damage due to TM administration, it may be preferable to use alternative euthanasia drugs when these risks could affect the objectives or outcomes of the research.

Comparison of masticatory muscle activity between young adults and elderly participants using a novel standardized bite device.

OBJECTIVES: Standardized bite training is required to prevent oral hypofunction in elderly individuals. We aimed to compare masticatory muscle activity between 24 young adults and 16 pre-elderly individuals during a biting task using a novel standardized bite device (BD). METHODS: The BD was made of silicone rubber and included a high-force or low-force plate spring or no plate spring (dummy). The compressive stiffness of the material in each BD was measured using a texture analyzer. All participants performed a biting task 50-times at a rate of 1/s each using the three types of BDs on the right first molar. Electromyographic (EMG) activity was recorded bilaterally from the masseter and temporalis muscles. The variability of each biting training session was calculated as the coefficient of variance (CV) from the EMG activity during each biting task for each muscle. Masticatory muscle fatigue was assessed using a numerical rating scale (NRS). RESULTS: Compressive stiffness was significantly different between each BD (P < 0.001). The CV and NRS scores were not significantly different between the groups. The EMG activities during each bite task in all muscles were not significantly different for any measurement item between the age groups. The EMG activities of high- and low-force BDs in the right temporalis (ipsilateral) muscle were significantly higher than those of the dummy BD (P < 0.001). CONCLUSIONS: Compressive stiffness of the BD affected EMG activity only in the ipsilateral temporalis muscle, but not in the masseter or contralateral temporalis muscles, without any age effect.

Analysis of definite awake bruxism using a portable electromyography device.

PURPOSE: This study aimed to compare awake bruxism events between subjective and objective evaluations using a questionnaire survey and a modified portable electromyography (EMG) device, and to examine correlations between sleep quality and awake bruxism. METHODS: The Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), and awareness of awake bruxism as clarified via interviews were conducted on 34 participants as subjective evaluations. The EMG device was used to record left temporal muscle activity for 6.5 h (from 09:00 to 15:30) and the number of awake bruxism episodes per hour. The participants were then classified into "bruxer" and "non-bruxer" groups based on the number of awake bruxism episodes. RESULTS: The mean number of awake bruxism episodes per hour was 33.6 ± 21.4, and 23% of the participants who reported having no awareness of awake bruxism in the interviews were defined as "bruxers" in the objective evaluations. In the bruxer group, positive correlations were found between the number of awake bruxism episodes and both ESS and PSQI scores. CONCLUSION: These findings suggest that objective measurements using a portable EMG device can increase the diagnostic accuracy for awake bruxism, and that sleep quality is a major risk factor for awake bruxism.