基本情報
論文
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The Journal of veterinary medical science 85(7) 715-720 2023年7月1日The efficacy of orally administered drugs in cattle is thought to be slow because of the anatomical and physiological features of their forestomach. Thus, parenteral routes are mainly preferred to administer drugs. However, the effect of some drugs with unique physicochemical properties was promptly obtained even after oral administration in clinically ill cattle. Therefore, the present study aimed to investigate pharmacokinetically the usefulness of the oral route in cattle by comparing the oral pharmacokinetic properties of two sulfonamides with different physicochemical properties. Sulfadiazine (SDZ) and sulfamonomethoxine (SMM) were administered by intravenous and oral route to four female Holstein cows with a 4-weeks washout period. Blood samples were collected over time, and SDZ and SMM concentrations in plasma were analyzed by HPLC. Data obtained from the same animal after intravenous and oral administration were simultaneously analyzed with the one compartment model, and kinetic parameters were calculated. The Tmax (mean ± SD) of SMM (2.75 ± 0.96 hr) was significantly achieved earlier than that of SDZ (5.00 ± 1.15 hr). Further, the mean absorption time of SMM (5.24 ± 0.69 hr) was significantly shorter than that of SDZ (5.92 ± 1.11 hr). Also, the half-life of absorption of SMM (3.91 ± 0.51 hr) was significantly shorter than that of SDZ (4.51 ± 0.82 hr). These data suggest that the absorption rates of highly unionized drugs (such as SMM) from the forestomach of cattle may be markedly higher than less unionized ones (such as SDZ).
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Veterinary Sciences 10(3) 231-231 2023年3月17日The objectives of this study were (1) to investigate the distribution of large (≥10 mm) follicle numbers during the estrous cycle and (2) to compare the timing of the estrus expression period after the ovarian examination between cows with one large follicle (1F) and two or more large follicles (2F) with functional corpus luteum (CL) at the ovarian examination in lactating Holstein dairy cows. In experiment 1, we performed 393 ovarian examinations by ultrasonography, addressed the existence of CL (≥20 mm) and large follicle numbers, and classified cows into 1F (n = 229) and 2F (n = 164) groups. The 1F appearance rates were beyond 75% each day during 3 to 12 d after estrus. However, 2F appearance rates were beyond 75% each day during 15 to 24 d after estrus. In experiment 2, we performed 302 ovarian examinations by ultrasonography and classified cows into the 1F (n = 168) and 2F (n = 134) groups. Estrus detection was performed for 24 d after the ovarian examination in each cow. In the 2F group, 75% of estrus occurred within 9 d of the ovarian examination. However, 75% of estrus occurred 10 d after the ovarian examination in 1F. Days from the ovarian examination to estrus were significantly shorter in the 2F (6.0 d; median, 7.2 ± 4.0 d; mean ± SD) than in the 1F (13 d, 12.4 ± 4.3 d) group. In conclusion, focusing on ≥10 mm follicle numbers with CL could be useful for predicting the estrus expression period.
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Veterinary sciences 9(12) 2022年12月17日Due to the high incidence of mammary tumors in dogs, it is important to elucidate the pathogenesis of these tumors in veterinary medicine. Radiation therapy is often used to treat mammary tumors that target DNA lesions. RAD51 is a key molecule that repairs DNA damage via homologous recombination. We examined the relationship between RAD51 expression and radiosensitivity in mammary tumor cell lines. CHMp and CHMm from the same individual were selected based on the differences in RAD51 expression. The radiosensitivity of both cell lines was examined using MTT and scratch assays; CHMm, which has high RAD51 expression, showed higher sensitivity to radiation than CHMp. However, the nuclear focus of RAD51 during DNA repair was formed normally in CHMp, but not in most of CHMm. Since irradiation resulted in the suppression of cell cycle progression in CHMp, the expression of p21, a cell cycle regulatory factor, was detected in CHMp after 15 Gy irradiation but not in CHMm. These results indicate that functional expression is more important than the quantitative expression of RAD51 in canine mammary tumor cells in response to DNA damage.
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Animals : an open access journal from MDPI 12(23) 2022年12月2日The objectives of this study were to assess the sequential dynamics of the endometrial polymorphonuclear cells (PMN) after calving by endometrial cytology, and clarify the factors that cause prolonged endometrial inflammation in lactating dairy cows. A total of 33 lactating Holstein dairy cows were used from -4 to 8 wk relative to calving (0 wk: the calving week). Endometrial samples were obtained sequentially from 2 to 8 wk. Body condition score and backfat thickness were obtained weekly from -4 to 8 wk. Blood samples collected from -4 to 8 wk were analyzed for indicators of energy status, hepatic function, systemic inflammation, and calcium. Blood amino acids were measured at 2 wk. Daily milk production was determined between 5 and 65 d postpartum. Based on the sequential cytological analysis, the endometrial inflammation threshold was set at ≥5.0% PMN, and the median wk of PMN% lower than 5.0% was 4.5 wk in this study; therefore, we classified the cows into the early group (cows with endometrial inflammation converged within 4 wk: n = 17) and the late group (cows with endometrial inflammation converged at or after 5 wk: n = 16). There were no differences in daily milk production, energy status, hepatic function, blood calcium concentration, and systemic inflammatory response. The late group had lower body condition scores and backfat thickness during the experimental period, and a higher blood concentration of 3-methyl histidine, indicating muscle breakdown, was observed in the late group at 2 wk. Our findings indicated that the lack of body fat reservation during the peripartum period and the increased muscle breakdown after calving were risk factors for prolonged endometrial inflammation.
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Viruses 14(8) 2022年8月6日Feline coronaviruses (FCoVs) infect cats worldwide and cause severe systemic diseases, such as feline infectious peritonitis (FIP). FIP has a high mortality rate, and drugs approved by the Food and Drug Administration have been ineffective for the treatment of FIP. Investigating host factors and the functions required for FCoV replication is necessary to develop effective drugs for the treatment of FIP. FCoV utilizes an endosomal trafficking system for cellular entry after binding between the viral spike (S) protein and its receptor. The cellular enzymes that cleave the S protein of FCoV to release the viral genome into the cytosol require an acidic pH optimized in the endosomes by regulating cellular ion concentrations. Ionophore antibiotics are compounds that form complexes with alkali ions to alter the endosomal pH conditions. This study shows that ionophore antibiotics, including valinomycin, salinomycin, and nigericin, inhibit FCoV proliferation in vitro in a dose-dependent manner. These results suggest that ionophore antibiotics should be investigated further as potential broad-spectrum anti-FCoV agents.
MISC
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日本平滑筋学会雑誌 16(1) "J-44" 2012年7月2日
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JOURNAL OF PHARMACOLOGICAL SCIENCES 118 206P-206P 2012年
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JOURNAL OF PHARMACOLOGICAL SCIENCES 112 207P-207P 2010年
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JAPANESE JOURNAL OF PHARMACOLOGY 88 146P-146P 2002年 査読有り
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Journal of Smooth Muscle Research Japanese Section 5(2) J69-J80 2001年8月1.In order to characterize prostanoid receptors in the non-pregnant porcine uterus, effects of naturally occurring PGs(PGD_2, PGE_2, PGE_1, PGF_<2α> PGI_2) and synthetic prostanoid receptor agonists (cloprostenol, BW-245C, iloprost) on contractility of longitudinal(LM) and circular muscles(CM) were examined in vitro. 2.PGD_2, PGE_2, PGE_1, PGF_<2α> and PGI_2 increased muscle contractility of the LM. The ranking order of potency was estimated to be PGF_<2α>≩PGE_2=PGE_1>PGD_2>PGI_2. On the contrary, PGE_1 and PGE_2 inhibited the muscle contractility at a high concentration (1-10μM). 3.PGD_2 inhibited the spontaneous contractions of the CM but PGE_2, PGE_1, PGF_<2α> and PGI_2 were less effective in causing the inhibition. The PGD_2-induced inhibition was potentiated by Ro20-1724 but not by zaprinast. PGD_2 treatment (for 5 min) significantly increased the tissue cyclic AMP level. 4.Cloprostenol (1 nM-10 μM) increased the contractility of both muscle layers but the LM was more sensitive to cloprostenol than the CM. 5.BW-245C (1 nM-10 μM) inhibited the spontaneous contractions of both muscle layers but the inhibition in the CM was more conspicuous than that in the LM. 6.Iloprost (10 nM-10 μM) increased the contractility of both muscle layers and these responses were not antagonized by SC19220 (5 μM). 7.Indomethacin (100 nM for 60 min) significantly decreased the frequency of spontaneous contractions in the LM. But spontaneous contractions in the CM were quitely insensitive to indomethacin. 8.The present results suggest that contractile (FP, EP_3) and relaxatory(DP, EP_2/EP_4) prostanoid receptors are present in the porcine myometrium in a muscle layer-dependent manner(FP, LM>CM ; DP, CM>LM). Endogeneous PGs involve in the initiation of spontaneous contractions in the LM.
共同研究・競争的資金等の研究課題
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日本学術振興会 科学研究費助成事業 2021年4月 - 2024年3月
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日本学術振興会 科学研究費助成事業 2012年4月 - 2016年3月
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日本学術振興会 科学研究費助成事業 2012年4月 - 2016年3月