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83.
In this study, we investigated the effect of multiple oral dosing of ketoconazole (KTZ) on pharmacokinetics of quinidine (QN), a CYP3A substrate with low hepatic clearance, after i.v. and oral administration in beagle dogs. Four dogs were given p.o. KTZ for 20 days (200 mg, b.i.d.). QN was administered either i.v. (1 mg/kg) or p.o. (100 mg) 10 and 20 days before the KTZ treatment and 10 and 20 days after start of KTZ treatment. Multiple oral dosing of KTZ decreased significantly alpha and beta, whereas increased t(1/2beta), V(1), and k(a). The KTZ treatment also decreased significantly both total body clearance (Cl(tot)) and oral clearance (Cl(oral)). No significant change in bioavailability was observed in the presence of KTZ. Co-administration of KTZ increased C(max) of QN to about 1.5-fold. Mean resident time after i.v. administration (MRT(i.v.)), and after oral administration (MRT(p.o.)) of QN were prolonged to about twofold, whereas mean absorption time (MAT) was decreased to 50%. Volume of distribution at steady state (V(d(ss))) of QN was unchanged in the presence of KTZ. These alterations may be because of a decrease in metabolism of QN by inhibition of KTZ on hepatic CYP3A activity. In conclusion, multiple oral dosing of KTZ affected largely pharmacokinetics of QN after i.v. and oral administration in beagle dogs. Therefore, KTZ at a clinical dosing regimen may markedly change the pharmacokinetics of drugs primarily metabolized by CYP3A with low hepatic clearance in dogs. In clinical use, much attention should be paid to concomitant administration of KTZ with the drug when given either p.o. or i.v.  相似文献   
84.
To determine the characters of receptors on target cells for avian rotaviruses, the receptors on MA104 cells for the pigeon rotavirus PO-13, the turkey rotaviruses Ty-1 and Ty-3, and the chicken rotavirus Ch-1 were analyzed. Pretreatment of MA104 cells with neuraminidase greatly reduced the infection by all of the four avian rotavirus strains. Binding of the cell-attachment protein, purified VP8 expressed in bacteria, of strain PO-13 to MA104 cells was also inhibited by pretreatment of cells with neuraminidase. These findings suggest that avian rotaviruses primarily utilize sialic acid-containing molecules as receptors on MA 104 cells.  相似文献   
85.
Differentiation of the histochemical characteristics of the olfactory receptor cells (ORC) was examined by immunohistochemistry for protein gene product 9.5 (PGP 9.5) and calretinin (CR) and lectin histochemistry for Phaseolus vulgaris agglutinin-L (PHA-L) in the developing olfactory epithelium (OE) of the barfin flounder. PGP 9.5 immunoreactivity was diffuse and CR immunoreactivity was restricted at day 7, but these immunoreactivities became intense in the OE toward day 91. Crypt cells were first identified at day 56. PHA-L staining was faint at day 28, but became intense toward day 91. These findings suggest that PGP 9.5-immunopositive cells, CR-immunopositive cells, crypt cells and PHA-L-reactive cells differentiate independently in the developing OE and constitute subsets of the ORC in the OE.  相似文献   
86.
The impact of acute phase response (APR) on the plasma clearances of antipyrine, theophylline, phenytoin and nifedipine was studied using 50 female rabbits. APR was induced by a bolus intramuscular injection of Escherichia coli lipopolysaccharide (LPS, 50 microg/kg). No abnormal findings, other than an increase in rectal body temperature and the plasma concentration of interleukin-6 (IL-6), were observed in the LPS-treated animals. Twenty-four hours after LPS injection, the pharmacokinetic parameters of the four drugs were obtained following intravenous administrations of antipyrine (7 mg/kg), theophylline (5 mg/kg), phenytoin (10 mg/kg) and nifedipine (1 mg/kg). Total body clearances of antipyrine, theophylline, phenytoin and nifedipine in LPS-treated rabbits decreased, and terminal elimination half-life and the mean residence time of these drugs increased compared with those in the control rabbits. The apparent volume of distribution for phenytoin and nifedipine increased after the LPS injection, although the binding percentage of the drugs with plasma protein did not change. These results suggested that APR appears to decrease the plasma clearances of these drugs in rabbits, which may be due to the suppression of the activity of cytochrome P450 enzymes.  相似文献   
87.
Bacterial strains isolated from the rhizosphere of angelica trees were evaluated for their antagonistic activity against Phytophthora cactorum, a causal agent of Phytophthora root rot. Of these, three bacterial strains, designated as T-1-8, T-1-14 and T-1-23, strongly inhibited mycelial growth of P. cactorum ARE-862 in a dual-culture plate assay. Biocontrol activity of these strains was then examined by dipping root of young seedlings of angelica trees into a bacterial suspension. The incidence of Phytophthora root rot was markedly suppressed for at least 79 days in pot tests when treated seedlings were planted in naturally infested soil. The suppression was maintained through June of the next year. In addition, these strains significantly reduced the development of Phytophthora root rot up to 47 days in naturally infested field and up to 63 days (the last day of testing) in an artificially (moderately) infested field. Based on their main bacteriological properties, strain T-1-14 was identified as Enterobacter cloacae and T-1-8 and T-1-23 were identified as Serratia ficaria. Received 5 July 1999/ Accepted in revised form 25 October 1999  相似文献   
88.
A variant of Cucumber mosaic virus, CMV(Y/GM2), was isolated from a tobacco plant with mild green mosaic symptoms that was regenerated in vitro from a yellow strain of CMV [CMV(Y)]-infected tobacco leaves by tissue culture. CMV(Y/GM2) has two amino acid substitutions at 36 and 111 positions in the coat protein encoded on RNA3. CMV, assembled by mixing in vitro transcribed CMV(Y) RNA1 and RNA2 plus infectious RNA3 transcribed in vitro from cDNA to RNA3 of CMV(Y/GM2), was prepared and designated as CMV(Y/GM2)tr. When tobacco (Nicotiana tabacum cv. Xanthi nc) plants were inoculated with CMV(Y/GM2)tr, large necrotic local lesions in which the virus was localized, developed on the inoculated leaves. This host response unique to CMV(Y/GM2)tr was similar to the hypersensitive response (HR), which is a common resistance response to avirulent pathogens and was observed in five cultivars of Nicotiana tabacum and eight Nicotiana species. The revertant virus, however, accumulated to quite different levels in the various hosts. CMV(Y/GM2)tr induced pathogenesis-related 1 (PR-1) protein accumulation and systemic acquired resistance (SAR) which were generally observed in the HR. However, when tobaccos were inoculated with CMV(S36P)tr and CMV(V111I)tr, which have an amino acid substitution at either the 36 or 111 position in the coat protein of CMV(Y), respectively, CMV(S36P)tr was restricted to the primary infection site without necrotic local lesion formation and PR-1 protein and SAR induction. CMV(V111I)tr, however, systemically spread and induced mild green mosaic symptoms, while the host had the HR to CMV(Y/GM2)tr. The localization of CMV(Y/GM2)tr at the primary infection site may not only be caused by the HR, but also by the restriction of virus systemic movement resulting from the amino acid substitution at position 36 in the coat protein of CMV(Y). Received 15 December 1999/ Accepted in revised form 18 April 2000  相似文献   
89.
Indole acetic acid (IAA) was believed to be an important regulator in xylem formation in conifers. However, few studies have been done on the endogenous amount of IAA in cambial region tissues in sugi (Cryptomeria japonica) trees. In this study, we report the IAA amounts in the lower and upper trunk of mature sugi cultivars (Kumotoshi, Yaichi and Obiaka) in September, and the effects of growth traits on the IAA amounts. The effect of height position (lower or upper trunk) on IAA amounts was found to be larger than that of genetic variation (Kumotoshi, Yaichi or Obiaka) by two-way ANOVA. There was no significant interaction effect (genetic variation × height position). The IAA amounts of all trees varied from 3 to 42 ng/cm2 at the lower trunk and 9 to 47 ng/cm2 at the upper trunk. Crown length and distance from crown base had significant positive and negative effects on IAA amounts in the trunk of sugi cultivars, respectively. Distance from crown base had a larger effect on IAA amounts than crown length. In Yaichi, taller trees had larger IAA amounts at both the lower and upper trunk.  相似文献   
90.
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