Previously, we reported that levels of chymase activity and its mRNA in cardiac tissues were significantly increased along with progression of cardiac fibrosis in cardiomyopathic hamsters, but the involvement of chymase in the progression of fibrosis has been unclear. In cultured human fibroblasts, the concentration of transforming growth factor- in the supernatant of medium was significantly increased after injection of human chymase. Furthermore, human chymase dose dependently increased cell proliferation, and this chymase-dependent proliferation was completely suppressed by a chymase inhibitor, Suc-Val-Pro-Phe p (OPh) 2 (10 M) or an anti-transforming growth factor- antibody (100 g/ml). In this study, we used Bio14.6 and F1B hamsters as cardiomyopathic and control hamsters, respectively. Cardiomyopathic hamsters were orally administered a novel chymase inhibitor, 4-[1-{[bis-(4-methylphenyl)-methyl]-carbamoyl}-3-(2-ethoxy-benzyl)-4-oxo-azetidine-2-yloxy]-benzoic acid (BCEAB; 100 mg/kg per day), or placebo from 5-to 45-week-old. In the placebo-treated group, the cardiac chymase activity in cardiomyopathic hamsters 45 weeks old was significantly increased compared with that in control hamsters. BCEAB significantly reduced the cardiac chymase activity. The indexes (ϩdP/dt and -dP/dt) of cardiac function were significantly improved by treatment with BCEAB. The mRNA levels of collagen I and collagen III in the placebotreated hamsters were significantly reduced to 69.6 and 76.5% by treatment with BCEAB, respectively. The fibrotic area in cardiac tissues in the BCEAB-treated hamsters was significantly suppressed to 50.7% compared with that in the placebo-treated treated hamsters. Therefore, the activation of transforming growth factor- by chymase may play an important role in the progression of cardiac fibrosis and cardiac dysfunction in cardiomyopathy.
The objectives of this study were to characterize early postpartum follicular dynamics in dairy cows in relation to their estrual activity and subsequent reproductive performance using 50 (26 primiparous and 24 multiparous) lactating Holstein cows. Ovaries and uterine horns of postpartum lactating cows were examined by ultrasonography 3 times weekly and continued until first services occurred after a 45-d voluntary waiting period. No differences were detected in fertility between primiparous and multiparous cows. In 40 of 50 cows, first postpartum ovulation was observed within 4 follicular waves, and the follicular wave patterns and ovarian cycles in most cows returned to normal as in cattle having normal estrous cycles after the second postpartum ovulation. Cows with the longest intervals from calving to first ovulation produced the most milk and also had prolonged intervals to first estrous activity. Differences in follicular dynamics before first ovulation altered intervals to first estrus, first service, and uterine involution, but these differences did not affect pregnancy rate, number of services, and days open. First postpartum insemination after 3 follicular waves tended to have greater pregnancy rates than those after 2 follicular waves. First inseminations at first estrus could produce greater pregnancy rates than those at subsequent periods of estrus.
Regarding cloned animals, interesting questions have been raised as to whether cloning restores cellular senescence undergone by their donor cells and how long cloned animals will be able to live. Focusing our attention on differences in telomere lengths depending on the tissue, we had produced 14 cloned cattle by using nuclei of donor cells derived from muscle, oviduct, mammary, and ear skin. Here, we show remarkable variation in telomere lengths among them using Southern blot analysis with telomere-specific probe. Telomere lengths in cloned cattle derived from muscle cells of an old bull were longer than those of a donor animal but were within the variation in normal calves. On the other hand, those derived from oviductal and mammary epithelial cells of an equally old cow were surprisingly shorter than any found in control cattle. The telomere lengths of cloned cattle derived from fibroblasts and oviductal epithelial cells of younger cattle showed the former and the latter results, respectively. In both cases, however, less telomere erosion or telomere extension from nuclear transfer to birth in most cloned cattle was observed in comparison with telomere erosion from fertilization to birth in control cattle. Embryonic cell-cloned cattle and their offspring calves were also shown to have telomeres longer than those in age-matched controls. These observations indicate that cloning does not necessarily restore the telomere clock but, rather, that nuclear transfer itself may commonly trigger an elongation of telomeres, probably more or less according to donor cell type. Remarkable variations among cloned cattle are suggested to be caused by variation in telomere length among donor cells and more or less elongation of telomere lengths induced by cloning.
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