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991.
992.
Uchida T Okumura K Ito T Kamiya H Nishimoto Y Yamada M Tomida T Matsui H Hayakawa T 《Clinical and experimental pharmacology & physiology》2002,29(5-6):381-385
1. Angiotensin-converting enzyme (ACE) inhibitors have been shown to improve insulin-resistance both experimentally and clinically. We therefore investigated the effects of quinapril, which has high tissue specificity for ACE, regarding the contribution of insulin to vascular contractions, as well as insulin sensitivity in a dietary rat model of insulin resistance. 2. Male Sprague-Dawley rats were divided into three groups: (i) rats fed normal chow (normal diet group); (ii) rats fed fructose-rich chow containing 40% fructose and 7% lard (fructose diet group); and (iii) rats fed fructose-rich chow plus quinapril (10 mg/kg per day; quinapril-treated group). 3. After 2 weeks, we evaluated systolic blood pressure, insulin sensitivity as assessed by steady state plasma glucose (SSPG) levels, response of aortic rings to phenylephrine (10-9 to 10-6 mol/L) in the presence or absence of insulin and the response of aortic rings to acetylcholine. 4. Feeding rats fructose-rich chow resulted in an elevation of blood pressure (P < 0.01) and SSPG levels (P < 0.01). Quinapril treatment significantly prevented increases in both blood pressure and SSPG, with a return to the levels seen in the normal diet group. 5. In the absence of insulin, the maximal contractile response to phenylephrine did not differ between the three groups. However, in the presence of insulin (100 mU/mL), the contractile response to phenylephrine (10-6 mol/L) was reduced by 22.8 +/- 1.2% in the normal diet group, although no insulin effects were observed in the fructose diet group (P < 0.01). Quinapril restored the inhibitory effect of insulin on phenylephrine-induced contractions. 6. In addition, the reduction in relaxation induced by acetylcholine in the fructose diet group was significantly reversed by quinapril treatment. 7. It is concluded that the fructose diet impairs the vasodilator effects of insulin as well as acetylcholine-induced relaxation in rat thoracic aortas. Quinapril prevented deterioration in the responses of the aortic rings, suggesting that ACE inhibitors may be useful for treating vascular insulin resistance. 相似文献
993.
Tagawa Y Minami S Yoshida T Tanaka K Sato S Goto Y Yamagata K 《Archiv der Pharmazie》2002,335(2-3):99-103
3-Methyl-1-phenylpyrazole-5-thiol (3a) and its p-nitro- (5) and p-fluorophenyl (8) derivatives were prepared as potential antimicrobial agents in relatively good yields. Compounds 3a and 8 showed good antibacterial activities against MRSA, S. aureus, S. epidermidis, E. faecalis, E. faecium, and S. pyogenes. Moreover, compound 3a also showed a synergistic effect with some aminoglycosides. 相似文献
994.
Watanabe T Hasegawa T Takahashi H Ishibashi T Itagaki H Sugibayashi K 《Pharmaceutical research》2002,19(5):669-675
Purpose. A cytotoxicity assay using a three-dimensional cultured human skin model, Living Skin Equivalent-high (LSE-high) was evaluated as an alternative to the Draize skin irritation tests using animals. A relation between the cytotoxicity and calculated concentration of an irritant in skin was also evaluated.
Methods. Colorimetric thiazoyl blue (MTT) conversion assay and a surfactant, cetylpyridinium chloride (CPC), were selected as a cytotoxicity assay and a model irritant. The fraction of dead cell number in the MTT assay or the Draize irritation score (in vitro and in vivo irritation data, respectively) was treated as a function of CPC concentration in the viable skin of LSE-high and guinea pig. Separately, in vitro permeations of CPC through the LSE-high or excised guinea pig skin were determined to calculate the average concentration of CPC in the viable skin using the Fickian diffusion theory. The obtained relations between the irritation scores and CPC concentration were evaluated by the Emax model (Hill equation).
Results. CPC concentration showing 50% irritation (IC
50) was similar for the MTT assay (18.9%) and Draize test (12.3%), and a good relationship (r = 0.981) was observed between the fraction of dead cell number and the Draize score. In contrast, IC
50, 1.32%, for the MTT assay in LSE-high was much lower than that using guinea pig skin. We then corrected the results for the MTT assay using a ratio of IC
50 in guinea pig skin against LSE-high, resulting in a good relation between both MTT results in guinea pig skin and LSE-high.
Conclusion. The present results suggest that the MTT assay using LSE-high may be utilized as an alternative for the Draize test in animals for evaluating skin irritation. 相似文献
995.
Ono M Idei N Nakajima T Itoh Y Kawakami N Shimada K Yamato S 《Journal of pharmaceutical and biomedical analysis》2002,29(1-2):325-334
An automated chromatographic detection system for the simultaneous determination of riboflavin phosphate, caffeine, nicotinamide and pyridoxine hydrochloride in a multivitamin pharmaceutical preparation was constructed. Hydrolytic pretreatment of riboflavin phosphate to riboflavin was carried out using a pre-column enzyme reactor, in which immobilized sweet potato acid phosphatase was packed, and then enzymatically hydrolyzed riboflavin and other ingredients in the pharmaceutical preparation were concentrated in an ODS trap column. The concentrated riboflavin and other ingredients were back-eluted from the trap column using a mobile phase containing 1-decanesulfonate as an ion-pair reagent, and then subsequently chromatographed on an ODS analytical column. It was necessary to wash the ODS trap column with aqueous acetonitrile to remove 1-decanesulfonate in the trap column, which is advantageous to concentrate the riboflavin and other ingredients for the subsequent analysis. The calibration curves for riboflavin phosphate and other ingredients were linear over the concentration ranges tested, and correlation coefficients for standard curves were 0.9999 for all four ingredients. Analytical recoveries of the four ingredients at different levels of concentration added to the ordinary pharmaceutical preparation were also in the range of 99.1-101.2%. The present method was superior to the ordinary manual and batch-wise enzymatic methods in being harmless to the environment, rapid and accurate under continuous autoanalysis. 相似文献
996.
Genetic characterization of hantaviruses transmitted by the Korean field mouse (Apodemus peninsulae), Far East Russia 总被引:7,自引:0,他引:7
Lokugamage K Kariwa H Hayasaka D Cui BZ Iwasaki T Lokugamage N Ivanov LI Volkov VI Demenev VA Slonova R Kompanets G Kushnaryova T Kurata T Maeda K Araki K Mizutani T Yoshimatsu K Arikawa J Takashima I 《Emerging infectious diseases》2002,8(8):768-776
In an epizootiologic survey of 122 rodents captured in Vladivostok, Russia, antibodies positive for hantavirus were found in Apodemus peninsulae (4/70), A. agrarius (1/39), and Clethrionomys rufocanus (1/8). The hantavirus sequences identified in two seropositive A. peninsulae and two patients with hemorrhagic fever with renal syndrome (HFRS) from the Primorye region of Far East Russia were designated as Solovey and Primorye, respectively. The nucleotide sequences of the Solovey, Primorye, and Amur (obtained through GenBank) sequences were closely related (>92% identity). Solovey and Primorye sequences shared 84% nucleotide identity with the prototype Hantaan 76-118. Phylogenetic analysis also indicated a close relationship between Solovey, Primorye, Amur, and other viruses identified in Russia, China, and Korea. Our findings suggest that the Korean field mouse (A. peninsulae) is the reservoir for a hantavirus that causes HFRS over a vast area of east Asia, including Far East Russia. 相似文献
997.
Kizaki T Suzuki K Ookawara T Izawa T Saitoh D Oh-Ishi S Suzuki K Haga S Ohno H 《Environmental health and preventive medicine》2002,6(4):218-228
Effects of environmental (cold) stress and aging on cells in monocyte/macrophage lineage were investigated. We demonstrated
that immune suppressive states seen in acute cold-stressed mice (8–10 weeks of age) is attributable to FcγRIIbright suppressor macrophages. Serum corticosterone levels were markedly increased in acute cold-stressed mice. In addition, expression
of glucocorticoids (GC) receptor mRNA was observed in FcγRIIbright cells from these mice. The increase of FcγRIIbright cells in peritoneal exudate cells caused by acute cold stress was inhibited by adrenalectomy or administration of a saturating
amount of the GC antagonist RU 38486 (mifepristone). On the contrary, administration of the GC agonist, dexamethasone, markedly
increased the proportion of FcγRIIbright cells in peritoneal exudate cells of control mice. These results suggest that the generation of FcγRIIbright suppressor cells of monocyte/macrophage lineage by acute cold stress was mediated by action of GC through the GC receptor.
We likewise found that the proportion of FcγRIIbright suppressor macrophages is increased in aged mice (22–24 months of age). Meanwhile, activated macrophages which function as
antigen presenting cells were decreased in aged rats. Both the basal corticosterone concentrations in serum and the expression
of mRNA for GC receptor in peritoneal macrophages increased significantly in aged animals, suggesting that these populational
and functional changes of macrophages in aged animals were mediated, in part, by the increased basal levels of GC. This is
probably being responsible for immunosenescence. 相似文献
998.
Pharmacological studies of diacerein in animal models of inflammation,arthritis and bone resorption 总被引:7,自引:0,他引:7
Diacerein has proved to be effective in the treatment of osteoarthritis. We investigated the effects of diacerein in animal models of carrageenin-, zymosan-, or dextran-induced paw edema and adjuvant-induced arthritis and in ovariectomized rats. In acute inflammatory models, unlike classical nonsteroidal anti-inflammatory drugs such as naproxen and ibuprofen, diacerein inhibited the rat paw edema induced by various agents. In the adjuvant-induced arthritic rats, diacerein at 100 mg/kg/day significantly suppressed the paw edema and the increase in serum mucoprotein. Addition of 3 mg/kg/day naproxen to each diacerein (3, 10, 30 mg/kg/day) dose resulted in significantly greater anti-inflammatory activity than with naproxen alone. In the ovariectomized rats, diacerein (10, 100 mg/kg/day) also significantly prevented bone loss and reduced the serum alkaline phosphatase and decreased the excretion of urinary hydroxyproline. In addition, rhein (10, 30 microM) inhibited calcium release from mouse calvaria induced by interleukin-1 beta, prostaglandin E(2) and parathyroid hormone 1-34 human fragment. These findings indicate that diacerein is a novel anti-inflammatory drug with pharmacological properties different from those of classical nonsteroidal anti-inflammatory drugs and support the clinical investigation of the use of combination therapy with diacerein and nonsteroidal anti-inflammatory drugs in patients with not only osteoarthritis but also rheumatoid arthritis. 相似文献
999.
The antinociceptive effects of pinacidil, an adenosine triphosphate (ATP)-sensitive K(+)i (K(ATP)) channel opener, were examined using the tail-flick test in non-diabetic and diabetic mice. Pinacidil i.c.v. produced dose-dependent antinociception in both non-diabetic and diabetic mice. There was no significant difference between the antinociceptive effect of i.c.v. pinacidil in non-diabetic mice and diabetic mice. The i.t. administration of pinacidil also produced dose-dependent antinociception in both non-diabetic and diabetic mice, however, the antinociceptive effect of i.t. pinacidil in diabetic mice was significantly greater than that in non-diabetic mice. The antinociceptive effect of i.c.v. or i.t. pinacidil was significantly antagonized by i.c.v. or i.t. glibenclamide, a K(ATP) channel blocker in both non-diabetic and diabetic mice. In non-diabetic mice, the antinociceptive effect of i.c.v. or i.t. administration of pinacidil was significantly antagonized by beta-funaltrexamine, a mu-opioid receptor antagonist, 7-benzylidenenaltrexone, a delta1-opioid receptor antagonist, naltriben, a delta2-opioid receptor antagonist, and nor-binaltorphimine, a kappa-opioid receptor antagonist. In diabetic mice, the antinociceptive effect of i.c.v. pinacidil was significantly reduced by 7-benzylidenenaltrexone, naltriben, and nor-binaltorphimine. However, beta-funaltrexamine had no effect on antinociception induced by i.c.v. pinacidil in diabetic mice. On the other hand, the antinociceptive effect of i.t. pinacidil was significantly antagonized by beta-funaltrexamine, 7-benzylidenenaltrexone, naltriben, and nor-binaltorphimine in diabetic mice. These results indicated that pinacidil produced antinociception through the release of opioid peptides acting at mu-, delta- and kappa-opioid receptors in surpraspinal and spinal cord of non-diabetic mice. On the other hand, in diabetic mice, the antinociception-induced by pinacidil was mediated through the release of opioid peptides acting at delta- and kappa-opioid receptors supraspinally, whereas pinacidil produced antinociception through the release of opioid peptides acting at mu-, delta-, and kappa-opioid receptors spinally. 相似文献
1000.
Nakahara T Yunoki M Mitani A Sakamoto K Ishii K 《Naunyn-Schmiedeberg's archives of pharmacology》2002,366(4):376-379
The influence of muscarinic M(2) receptors to modulate the relaxant effects of atrial natriuretic peptide (ANP) and sodium nitroprusside (SNP) was investigated in bovine tracheal smooth muscle. In bovine tracheal smooth muscles contracted with methacholine (0.3 micro M), methoctramine (0.03 micro M), a selective muscarinic M(2) receptor antagonist, augmented the relaxant responses to ANP without affecting the responses to SNP and 8-(4-chlorophenylthio)guanosine 3',5'-cyclic monophosphate. Pertussis toxin (PTX; 200 ng/ml for 18 h) augmented the relaxation and accumulation of guanosine 3',5'-cyclic monophosphate produced by ANP. These results suggest that the stimulation of muscarinic M(2) receptors suppresses ANP-induced activation of particulate guanylyl cyclase via a PTX-sensitive G protein. 相似文献