Spironolactone, but not Eplerenone, Impairs Glucose Tolerance in a Rat Model of Metabolic Syndrome     

Homma T  Fujisawa M  Arai K  Ishii M  Sada T  Ikeda M 《The Journal of veterinary medical science / the Japanese Society of Veterinary Science》2012,74(8):1015-1022

Although some clinical studies have suggested that spironolactone (SPL), a mineralocorticoid receptor (MR) antagonist, appears to increase the blood glucose levels, experimental studies have not supported this notion. Here, we investigated the effect of SPL on blood glucose levels in SHR/NDmcr-cp(cp/cp) (ND) rats, an animal model of metabolic syndrome, in comparison with that of eplerenone (EPL), another MR antagonist. At the same dose of 100 mg/kg, SPL and EPL increased the urinary sodium-to-potassium ratio to a comparable extent, indicating that both agents have similar renal MR antagonistic efficacy in ND rats. Interestingly, SPL but not EPL significantly increased the level of blood glucose. The oral glucose tolerance test revealed that treatment with SPL led to glucose intolerance. The levels of serum insulin and adiponectin, regulators of the blood glucose level, were virtually unaffected by treatment with SPL. On the other hand, SPL induced a marked increase in the blood level of aldosterone, known to be a risk factor for insulin resistance. These results demonstrate that in comparison with EPL, SPL characteristically impairs glucose tolerance in an animal model of metabolic syndrome, in association with a higher blood level of aldosterone.  相似文献   

Evaluation of myelotoxicity in dietary restricted rats     

Miyata H  Asanuma F  Iwaki Y  Kimura M  Matsumoto K 《Journal of toxicologic pathology》2009,22(1):53-63

The purpose of this study was to clarify the effect of decreased food consumption on evaluation of myelotoxicity in routine general toxicity studies. Male rats were divided into the following 7 groups: 12, 15, and 18 mg/kg 5-fluorouracil (5-FU) treatment groups (FU12, FU15 and FU18); dietary restriction groups (R12, R15 and R18 receiving the same amount of food as the rats in the FU12, FU15 and FU18 groups, respectively); and a nontreated control group (NT). We compared the changes in body weight, hematology and the results of cytological analyses of bone marrow and histopathology among the groups after administration and recovery periods of 14 and 7 days, respectively. At the end of the administration period, the FU15 and FU18 groups showed decreases in many hematologic and bone marrow parameters that were all similar to those in the corresponding dietary restriction groups (R15 and R18). A granulocyte abnormality (polyploidy: frequency of 1% or less) was also observed in all 5-FU treated groups. At the end of the recovery period, increases in the reticulocyte and platelet counts and extramedullary hematopoiesis of the spleen were observed in the 5-FU treated groups. These results indicate that the results of general toxicity studies in rats should be evaluated in consideration of dietary restriction effects when food consumption is decreased at about 30-40% or more. Careful morphological observation of hemocytes would be helpful in distinguishing the effect of a drug from that of dietary restriction in relation to hematological and bone marrow parameters. Performance of a recovery test to determine the reactive response of hematopoiesis is also recommended.  相似文献   

Purification and characterization of cathepsin S from hepatopancreas of carp Cyprinus carpio     

Henneke Pangkey  Keniji Hara  Katsuyasu Tachibana  Min-Jie Cao  Kiyoshi Osatomi and  Tadashi Ishihara 《Fisheries Science》2000,66(6):1130-1137

SUMMARY: Cathepsin S was purified from carp hepatopancreas to homogeneity up to 300-fold. The amino acid sequence of its NH₂-terminus was determined to be V-P-D-A-M-D-W-Y-N-K-G-Y-V-T-D-V-K-N-Q. On the contrary, that of purified cathepsin L from carp hepatopancreas was to be V-P-N-S-L-D-W-R-E-K-G. Purified cathepsin S consisted of a single chain with 37 kDa estimated by sodium dodecylsulfate–polyacrylamide gel electrophoresis. The enzyme had strong hydrolytic activity toward Z-Phe-Arg-MCA with the pH optimum of 7.0, but this lacked the ability to hydrolyze most of the other MCA substrates. The optimum pH of cathepsin S for protein substrate (carp myosin heavy chain) was also to be pH 7.0. These properties of purified cathepsin S obviously differ from cathepsins B and L. The enzyme activity was totally inhibited by E-64, leupeptin, 5–5'-dithiobis (2-nitro-benzoic acid) and p -tosyl-lys chloromethylketone as well.  相似文献   

Molecular cloning of the canine nicotinic acetylcholine receptor alpha-subunit gene and development of the ELISA method to diagnose myasthenia gravis     

Yoshioka T  Uzuka Y  Tanabe S  Sarashina T  Ishiguro N 《Veterinary immunology and immunopathology》1999,72(3-4):315-324

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Polymorphisms of caprine PrP gene detected in Japan     

Kurosaki Y  Ishiguro N  Horiuchi M  Shinagawa M 《The Journal of veterinary medical science / the Japanese Society of Veterinary Science》2005,67(3):321-323

Polymorphism of the PrP gene is a primary factor influencing susceptibility and incubation period in natural and experimental scrapie in sheep and goats. Polymorphisms of the caprine PrP gene in Japan were examined in 118 goats. Eight allelic variants and 19 genotypes were obtained. Amino acid polymorphisms were observed at 7 codons: 102, 142, 143, 240, 127, 146 and 211 (the latter 3 are novel polymorphisms). The polymorphisms at codons 142M and 143R, which are associated with the resistance to scrapie, were relatively rare in the present study. Thus, the present results provide information about the caprine PrP gene that may be useful for assessing the risk of goat scrapie.  相似文献   

Japanese black cattle with ateliosis showed lower insulin responses during glucose tolerance test     

Takasu M  Ohba Y  Hagiwara Y  Hosoda I  Nishii N  Kitoh K  Miyazawa K  Kitagawa H 《The Journal of veterinary medical science / the Japanese Society of Veterinary Science》2005,67(6):635-637

In order to determine insulin secretability and glucose utilization, a glucose tolerance test was performed in ateliotic cattle of 2 paternal strains; MHO and HSK cattle. MHO and HSK cattle showed different endocrine patterns in our previous study. Area under the insulin concentration curves (insulin-AUC) in the ateliotic cattle were significantly lower (122.3 +/- 59.4 ng.min/ml and 99.2 +/- 24.8 ng.min/ml for MHO and HSK cattle, respectively) than the control cattle (420.2 +/- 175.2 ng.min/ml). These low insulin responses to GTT may have an influence on growth retardation in MHO and HSK cattle.  相似文献   

Tumor necrosis factor-alpha (TNF alpha) inhibits progesterone and estradiol-17beta production from cultured granulosa cells: presence of TNFalpha receptors in bovine granulosa and theca cells     

Sakumoto R  Shibaya M  Okuda K 《The Journal of reproduction and development》2003,49(6):441-449

The aim of this study was to investigate whether functional tumor necrosis factor-alpha (TNFalpha) receptors are present in the granulosa cells and the cells of theca interna (theca cells), obtained from bovine follicles classified into one of three groups. Each group was defined as either small vesicular ovarian follicles (small follicles; 3-5 mm in diameter), preovulatory mature ovarian follicles (preovulatory follicles) or atretic follicles (12-18 mm) according to gross examination of the corpus luteum in the epsilateral or contralateral ovary and the uterus (size, color, consistency and mucus), and the ratio of progesterone (P(4)) and estradiol-17beta (E(2)) concentrations in follicular fluid. A Scatchard analysis showed the presence of a high-affinity binding site on both granulosa and theca cells from all follicles examined (dissociation constant: 4.7 +/- 0.15 to 6.9 +/- 1.40 nM). Moreover, TNFalpha receptor concentrations in granulosa and theca cells obtained from atretic follicles were significantly higher than those in the cells from preovulatory follicles (P<0.05). Exposure of cultured granulosa cells from small antral follicles to recombinant human TNFalpha (rhTNFalpha; 0.06-6 nM) inhibited E(2) secretion in a dose-dependent fashion (P<0.01), but did not affect P(4) secretion. In addition, rhTNFalpha inhibited follicle stimulating hormone-, forskolin- or dibutylyl cyclic AMP-induced P(4) and E(2) secretion by the cells (P<0.01). These results indicate the presence of functional TNFalpha receptors in bovine granulosa and theca cells in small, preovulatory and atretic follicles, and suggest that TNFalpha plays a role in regulating their secretory function.  相似文献   

Biological activity of recombinant bovine interferon tau using an Autographa californica nuclear polyhedrosis virus expression system     

Takahashi H  Inumaru S  Takahashi M  Watanabe S  Iga K  Yokomizo Y  Geshi M  Okano A  Okuda K 《The Journal of reproduction and development》2003,49(6):433-440

Bovine interferon (bIFN) tau, which plays a key role in maternal-fetal recognition of pregnancy, was expressed by an Autographa californica nuclear polyhedrosis virus expression system. cDNA coding bIFNtau was derived from cultured trophoblast cells. The recombinant (r) bIFNtau had high antiviral activity (1 x 10 (8) IU/mg) and the molecular weight of rbIFNtau was estimated to be 23 kDa by Western blotting analysis. We investigated the biological effect of rbIFNtau on prostaglandin (PG) F(2alpha) synthesis in cultured bovine endometrial epithelial cells in the presence or absence of oxytocin (OT, 100 nM). rbIFNtau suppressed basal and OT-induced PGF(2alpha) production in a dose-dependent manner (1-1,000 ng/ml). These results showed that biologically active rbIFNtau was produced in the baculovirus expression system, and that rbIFNtau had the ability to suppress the synthesis of PGF(2alpha) from bovine endometrial epithelial cells.  相似文献   

A passage and storage system for isolated bovine endometrial epithelial and stromal cells     

Murakami S  Shibaya M  Takeuchi K  Skarzynski DJ  Okuda K 《The Journal of reproduction and development》2003,49(6):531-538

To establish a storage system for isolated endometrial cells, we investigated the basal, oxytocin (OT)- and tumor necrosis factor (TNF) alpha-stimulated production of prostaglandin (PG) F(2alpha) in bovine-passaged and frozen-thawed endometrial cells. Stromal and epithelial cells obtained from cows in the early stage of the estrous cycle (Days 2-5) were frozen at -80 C or further cultured and/or passaged until passage 4 in DMEM/Ham's F-12 supplemented with 10% calf serum. A fresh-unfrozen primary culture and one-time passaged fresh-unfrozen cells were used as the control. When both unfrozen and frozen cells reached confluence, the culture medium was replaced with fresh medium with 0.1% BSA and the cells were stimulated with OT (100 ng/ml) or TNFalpha (1 ng/ml) for 4 h. The passage and freezing of the endometrial cells did not affect their morphology. In primary culture of frozen and unfrozen endometrial cells, OT strongly stimulated PGF(2alpha) production in epithelial cells, and TNFalpha strongly stimulated PGF(2alpha) production in stromal cells (P<0.05). The basal output of PGF(2alpha) in frozen stromal cells was similar to that in unfrozen stromal cells. However, the basal output of PGF(2alpha) in frozen epithelial cells was significantly lower than that unfrozen cells (P<0.05). On the other hand, in passaged cells, the basal level of PGF(2alpha) production was retained until passage 1 in epithelial cells, whereas it was retained until passage 4 in stromal cells. Although epithelial cells responded to OT in PGF(2alpha) production until passage 2 (P<0.05), the stromal cells showed a significant response to TNFalpha until passage 4 (P<0.05). These results suggest that stored cells could be used for studying the physiology of bovine endometrium in vitro until passage 1 in endometrial epithelial cells, and until passage 4 in stromal cells.  相似文献   

Preventive effect of hyaluronic acid on the suppression of attachment and migration abilities of bovine chondrocytes by IL-1alpha in vitro     

Kim G  Okumura M  Ishiguro T  Kadosawa T  Fujinaga T 《The Journal of veterinary medical science / the Japanese Society of Veterinary Science》2003,65(3):427-430

Attachment and migration of bovine chondrocytes cultured in vitro were significantly suppressed by the addition of interleukin (IL)-1alpha at the concentration of 1 ng/ml or more (p<0.05). The application of hyaluronic acid (HA) at the concentration of 10 micro g/m l or more significantly recovered the attachment of chondrocytes (p<0.05) and the application of HA at 100 micro g/ml concentration recovered the migration of chondrocytes suppressed by IL-1alpha. These results suggest that the application of HA for inflammatory arthropathies or chondrocyte transplantation might be helpful to preserve the properties of chondrocytes and its extracellular matrix against inflammatory conditions.  相似文献