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2.
Stanislw Ryng Zdzislw Machn Zbigniew Wieczorek Michal Zimecki Tadeusz Glowiak 《Archiv der Pharmazie》1997,330(11):319-326
A series of 5-aminomethinimino-3-methyl-4-isoxazolecarboxylic acid phenylamides 4 has been prepared by condensation of 5-amino-3-methyl-4-isoxazolecarboxylic acid phenylamides 1 with trichloroacetic aldehyde. Alcoholysis of trichloro derivatives 2 gave 5-alkoxymethine derivatives 3 which, on reaction with an appropriate amine, formed the corresponding compounds 4 . The compounds obtained were evaluated for their immunological activity. The properties of three compounds, described in this report, permitted inhibition of the immune response in all possible ways: diminishing both types of immune response ( 4d ), humoral immune response ( 4a ), or cellular immune response ( 4c ). Preparation 4d is comparable in its effectiveness to CsA, so it may be potentially used as an agent for prolongation of the function of transplanted organs. Two other compounds may potentially be used in cases where only one type the immune response is required for combating pathogen invasion. 相似文献
3.
K Olczyk E J Kucharz M Wieczorek M Szczebara P Sonecki 《Arhiv za higijenu rada i toksikologiju》1990,41(1):1-6
Intoxication of rats with mercuric chloride (0.5 mg Hg/kg of body weight, daily for 10 weeks) increased the hepatic contents of soluble and insoluble collagen and elastin. The increase was associated with elevated serum aminotransferase and alkaline phosphatase activities, and decreased total protein level in serum. Inflammatory changes were found in the liver. An increase in the fibrous protein content suggests that inflammatory reaction to mercuric chloride can result in hepatic fibrosis. 相似文献
4.
Several areas related to the use of telescopes in low vision are reviewed. These include: contrast sensitivity function; eccentric viewing through a telescope; field of view; telescope used in reverse; and IOL-spectacle lens telescopic systems. Experimental data are included to support selected clinical observations routinely made by low vision clinicians. 相似文献
5.
Non-competitive, sandwich enzyme immunoassay for both penicillin amidases from Escherichia coli is described. The assay involves the use of monospecific antibodies and their conjugates. The amidases inactivated by heating and by acid- or alkali-treatment cannot be assayed. Reproducible results for each amidase were achieved within 5-6 hours in the range of 3-500 ng/ml (0.25-40 mU/ml) and coefficient of variation was 13%. 相似文献
6.
Interleukin–2 and hyperthermia have been used individually to treat a variety of tumors in both experimental and human trials. Combined adoptive immunotherapy and hyperthermia is an exciting new line of investigation. Previous work in our laboratory has shown that combined local hyperthermia and rIL-2 therapy can significantly decrease the rate of tumor growth. In this study, we investigated the effect of combined whole-body hyperthermia (WBHT) and rIL-2 on the growth of subcutaneous MCA-105 murine tumors in C57BL/6 mice. Treatment of both microscopic (day 3) and macroscopic (day 10) tumors was evaluated. In the treatment of microscopic tumors, animals received either no treatment; rIL-2 (3 × 105 IU ip tid) on days 3–7; plus WBHT(41°C for 30 min) on days 3, 5, and 7; or WBHT only on days 3, 5, and 7. In treating macroscopic tumors, animals received either no treatment; rIL-2 on days 10–14; plus WBHT on days 10, 12, and 14; or WBHT only on days 10, 12, and 14. While combined treatment and WBHT alone had no significant effect on the growth of microscopic tumors, combined IL-2 and WBHT significantly reduced the rate of tumor growth of macroscopic tumors. These results suggest that the tumor microenvironment plays a critical role in combined WBHT and rIL-2 therapy, and may be due to effects of WBHT on the tumor vasculature. © 1993 Wiley-Liss, Inc. 相似文献
7.
Adult Toxocara canis and Ascaris suum were incubated in vitro in media containing 0.1, 1, 10 or 100 µg/ml flubendazole in order to study drug-derived effects. This incubation was done for 8 h and repeated (in some groups) after 24 h for another 8 h. The onset and intensity of flubendazole-derived effects were dosage-dependent and time-dependent, i.e. the same grade of damage was reached when incubating for a longer period at a low dosage or for a shorter period in medium containing a high amount (10 or 100 µg/ml) of flubendazole. A repeated incubation in drug-containing medium was superior to a single exposure. Flubendazole is apparently able to penetrate into the worm's interior via the cuticle. This became evident in worms with sealed orifices, which showed identical damage to worms which were not sealed. The type of tissue damage due to flubendazole was identical in both worm species when exposed to any of the drug dosages used. The principal mode of action of flubendazole was based on the complete reduction of microtubuli-polymerisation inside the parasite's cells. This apparently led to the complete destruction of the hypodermis, muscle layer and intestine. Flubendazole also stopped the formation of gametes. Summarising, even low concentrations of flubendazole (0.1 µg/ml) led to significant and irreversible damage in all worms studied. 相似文献
8.
Dagmar Busse Jose Cosme Philippe Beaune Heyo K. Kroemer Michel Eichelbaum D. Busse H. K. Kroemer M. Eichelbaum 《Naunyn-Schmiedeberg's archives of pharmacology》1995,353(1):116-121
The calcium channel blocker verapamil [2,8-bis-(3,4-dimethoxyphenyl)-6-methyl-2-isopropyl-6-azaoctanitrile] undergoes extensive biotransformation in man. We have previously demonstrated cytochrome P450 (CYP) 3A4 and 1A2 to be the enzymes responsible for verapamil N-dealkylation (formation of D-617 [2-(3,4-dimethoxyphenyl)-5-methylamino-2-isopropylvaleronitrile]), and verapamil N-demethylation (formation of norverapamil [2,8-bis(3,4-dimethoxyphenyl)-2-isopropyl-6-azaoctanitrile]), while there was no involvement of CYP3A4 and CYP1A2 in the third initial metabolic step of verapamil, which is verapamil O-demethylation. This pathway yields formation of D-703 [2-(4-hydroxy-3-methoxyphenyl)-8-(3,4-dimethoxyphenyl)-6-methyl-2-isopropyl-6-azaoctanitrile] and D-702 [2-(3,4-dimethoxyphenyl)-8-(4-hydroxy-3-methoxyphenyl)6-methyl-2-isopropyl-6-azaoctanitrile]. The enzymes catalyzing verapamil O-demethylation have not been characterized so far. We have therefore identified and characterized the enzymes involved in verapamil O-demethylation in humans by using the following in vitro approaches: (I) characterization of O-demethylation kinetics in the presence of the microsomal fraction of human liver, (II) inhibition of verapamil O-demethylation by specific antibodies and selective inhibitors and (111) investigation of metabolite formation in microsomes obtained from yeast strain Saccharomyces cerevisiae W(R), that was genetically engineered for stable expression of human CYP2C8, 2C9 and 2C18.In human liver microsomes (n=4), the intrinsic clearance (CLint), as derived from the ratio of V
max/Km, was significantly higher for O-demethylation to D-703 compared to formation of D-702 following incubation with racemic verapamil (13.9±1.0 vs 2.4±0.6 ml*min-1
*g-1 mean±SD; p<0.05), S-Verapamil (16.8±3.3 vs 2.2±1.2 ml* mini*g-1, p<0.05) and R-verapamil (12.1±2.9 vs 3.6 ±1.3 ml*min-1
* g-1; p<0.05), thus indicating regioselectivity of verapamil O-demethylation process. The CLint of D-703 formation in human liver microsomes showed a modest but significant degree of stereo selectivity (p<0.05) with a S/R-ratio of 1.41±0.17. Anti-LKM2 (anti-liver/kidney microsome) autoantibodies (which inhibit CYP2C9 and 2C19) and sulfaphenazole (a specific CYP2C9 inhibitor) reduced the maximum rate of formation of D-703 by 81.5±4.5% and 45%, that of D-702 by 52.7±7.5% and 72.5%, respectively. Both D-703 and D-702 were formed by stably expressed CYP2C9 and CYP2C18, whereas incubation with CYP2C8 selectively yielded D-703.In conclusion, our results show that enzymes of the CYP2C subfamily are mainly involved in verapamil O-demethylation. Verapamil therefore has the potential to interact with other drugs which inhibit or induce these enzymes. 相似文献
9.
Alexandra Kautzky-Willer Dagmar Bancher-Todesca 《Wiener Medizinische Wochenschrift》2003,153(21-22):478-484
10.
Differential increases in brain levels of neuropeptide Y and vasoactive intestinal polypeptide after kainic acid-induced seizures in the rat 总被引:7,自引:0,他引:7
Josef Marksteiner Günther Sperk Dagmar Maas 《Naunyn-Schmiedeberg's archives of pharmacology》1989,339(1-2):173-177
Summary Changes in immunoreactivities of neuropeptide Y (NPY) and vasoactive intestinal polypeptide (VIP) were investigated in the brain of rats after severe kainic acid (KA, 10 mg/kg, i.p.) induced limbic seizures. Decreased levels of both neuropeptides were observed in the frontal cortex, striatum, dorsal hippocampus and amygdala/pyriform cortex subsequently to the period of acute seizures (3 h after injection of the toxin). Then NPY increased consistently in the frontal cortex, hippocampus and amygdala/pyriform cortex. Highest levels (290% of controls) were found in the frontal cortex after two months. Anticonvulsant therapy with phenobarbital (20 mg/kg, i.p., twice daily for three weeks) partially suppressed the rise in NPY levels. Immunoreactivity of VIP increased (to 150%) in the frontal cortex only transiently 3 days after injection of kainic acid. At the subsequently examined time intervals (10–60 days after kainic acid) it declined to control values. Levels decreasing subsequently to acute seizures reflect increased release and degradation of the respective peptide. Increased NPY levels suggest upregulation of NPY/ somatostatin/GABA neurons due to the decreased seizure threshold of the animals. The early, reversible rise of VIP in the cortex points to a short-lasting activation of this peptide system contained in local cholinergic neurons. This may be a consequence either of the acute seizures or subsequent neuropathological changes.
Send offprint requests to G. Sperk at the above address 相似文献