Spontaneous Age-Related Histopathological Changes in Microminipigs.

Microminipigs have become an attractive animal model for toxicology and pharmacology studies and for human disease models, owing to their manageable size. Although there are numerous reports of spontaneous age-related lesions in mice, rats, dogs, and monkeys, those in minipigs are scarce. In the present study, spontaneous age-related histopathological changes were investigated using 37 microminipigs (20 males and 17 females) that were 6 months to 10 years of age. Abnormal deposits of materials were evident in several animals from 6 years of age, and these deposits included amyloid in the renal medulla, thyroid gland, and adrenal gland, hyaline droplets in glomeruli, and fibrillar inclusions in neurons. Arterial sclerosing changes (intimal thickening, intimal proliferation, and medial mineralization) and proliferative lesions (hyperplasia of hepatocytes, follicular cells, Leydig cells, and uterine endometrial glands) were present at 4 years of age and beyond. Renal adenoma, uterine leiomyoma, and Leydig cell tumor were observed in several microminipigs. Moreover, glomerulosclerosis, renal interstitial fibrosis, thymic involution, and adrenocortical cell vacuolation were common in aging microminipigs. Since knowledge of age-related changes is helpful for pathologists, the basic information obtained in this study will be a useful reference for all future toxicity evaluations in microminipigs.

Contact-free unconstraint respiratory measurements with load cells under the bed in awake healthy volunteers: breath-by-breath comparison with pneumotachography.

Rate of respiration is a fundamental vital sign. Accuracy and precision of respiratory rate measurements with contact-free load cell sensors under the bed legs were assessed by breath-by-breath comparison with the pneumotachography technique during two different dynamic breathing tasks in 16 awake human adults resting on the bed. The subject voluntarily increased and decreased the respiratory rate between 4 and 16 breaths/min (n = 8) and 10 and 40 breaths/min (n = 8) at every 2 breaths in 6 different lying postures such as supine, left lateral, right lateral, and 30, 45, and 60° sitting postures. Reciprocal phase changes of the upper and lower load cell signals accorded with the respiratory phases indicating respiratory-related shifts of the centroid along the long axis of the bed. Bland-Altman analyses revealed 0.66 and 1.59 breaths/min standard deviation differences between the techniques (limits of agreement: -1.22 to 1.36 and -2.96 to 3.30) and 0.07 and 0.17 breaths/min fixed bias differences (accuracy) (confidence interval: 0.04 to 0.10 and 0.12 to 0.22) for the mean respiratory rates of 10.5 ± 3.7 and 24.6 ± 8.9 breaths/min, respectively, regardless of the body postures on the bed. Proportional underestimation by this technique was evident for respiratory rates >40 breaths/min. Sample breath increase up to 10 breaths improved the precision from 1.59 to 0.26 breaths/min. Abnormally faster and slower respirations were accurately detected. We conclude that contact-free unconstraint respiratory rate measurements with load cells under the bed legs are accurate and may serve as a new clinical and investigational tool. NEW & NOTEWORTHY Four load cells placed under the bed legs successfully captured a centroid shift during respiration in human subjects lying on a bed. Breath-by-breath comparison of the breaths covering a wide respiratory rate range by pneumotachography confirmed reliability of the contact-free unconstraint respiratory rate measurements by small standard deviations and biases regardless of body postures. Abnormally faster and slower respirations were accurately detected. This technique should be an asset as a new clinical and investigational tool.

Genetic association of swine leukocyte antigen class II haplotypes and body weight in Microminipigs.

OBJECTIVE: Microminipigs are a novel animal model with extensive applications in laboratory studies owing, in part, to their extremely small body sizes. In this study, the relationship between swine leukocyte antigen (SLA) class II haplotype and body weight was evaluated in the Microminipig population. METHODS: A total of 1,900 haplotypes, covering SLA class II haplotypes Lr-0.7, Lr-0.23, Lr-0.17, Lr-0.37, Lr-0.16, Lr-0.11, Lr-0.13, and Lr-0.18, were analyzed in 950 piglets. Birth weights and weights on postnatal day 50 were examined in piglets with eight different SLA class II haplotypes. RESULTS: The mean birth weight of piglets with the Lr-0.23 haplotype (0.415 kg, n = 702) was significantly lower than that of piglets with Lr-0.17 (0.445 kg, n = 328) and Lr-0.37 (0.438 kg, n = 383) haplotypes. At postnatal day 50, the mean body weight of piglets with the Lr-0.23 haplotype (3.14 kg) was significantly lower than that of piglets with the Lr-0.13 haplotype (3.46 kg, p<0.01). There were no significant differences in daily gains (DGs) among the eight haplotypes. However, piglets with the Lr-0.11 and -0.18 haplotype combination or any heterozygous haplotype combinations containing Lr-0.23 had significantly lower DGs than those of piglets with the Lr-0.18, 0.37 haplotype combination. CONCLUSION: Piglets with the Lr-0.23 haplotype had relatively low body weights at birth and on postnatal day 50 and slightly lower DGs than those of piglets with other haplotypes. Therefore, the Lr-0.23 SLA class II haplotype may be a suitable marker for the selective breeding of Microminipigs with small body sizes.