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991.
In a retrospective study, 18 patients aged between 17 and 65 were examined between 12 and 23 months after successful surgery for retinal detachment with detached macular region. Visual acuity, refraction, steropsis, fusion and aniseikonia were determined. Visual acuity in the eyes operated on was between 0.1 and 1.0, refractive changes ranged from 0 to 4 D. No disturbances of binocular function resulting from acquired aniseikonia were found. Postoperatively acquired strabismus was diagnosed in three patients. Good to very good steropsis (30-240") was found with the TNO test, while fusion was reduced in some cases; even suppression was found, for small objects (1 degrees). The results are discussed in the light of the pathophysiological changes following retinal detachment including detachment of the macular area. 相似文献
992.
993.
A case of hyaline membrane disease was treated successfully with pulmonary surfactant (PS) isolated from human amniotic fluid. Dosage was 150 mg phospholipid/kg. The exogenous surfactant was instilled into the airway via a tracheal cannula. Clinical symptoms, PO2 and FiO2 improved evidently 24 hours after administration. L/S ratio and phosphatidylglycerol recovered gradually in aspirates. Lung X-ray film manifested "white lung" before instillation of surfactant and showed a striking improvement 3 days after treatment. The duration of mechanical ventilation was 6 days. During the period of recovery complications of patent ductus arteriosus and bacterial pneumonia developed. However, the patient recovered completely and was discharged 32 days after admission. 相似文献
994.
Lipophilic analogues of sparsomycin as strong inhibitors of protein synthesis and tumor growth: a structure-activity relationship study 总被引:2,自引:0,他引:2
L A van den Broek E Lázaro Z Zylicz P J Fennis F A Missler P Lelieveld M Garzotto D J Wagener J P Ballesta H C Ottenheijm 《Journal of medicinal chemistry》1989,32(8):2002-2015
Fourteen derivatives of sparsomycin (1) were synthesized. Six of them were prepared following a novel synthetic route starting from the L-amino acid alanine. Some physicochemical properties, viz. lipophilicity and water solubility, of selected derivatives were measured. The biological activity was tested in vitro in cell-free protein synthesis inhibition assays, in bacterial and tumor cell growth inhibition assays, and in the L1210 leukemia in vivo model in mice. Also for selected drugs the acute toxicity in mice was determined. Ribosomes from both an eukaryotic and a prokaryotic organism were used in the protein synthesis inhibition systems. A linear correlation between the lipophilicity parameters measured was observed. Water solubility and drug toxicity in mice were found to be linearly correlated with lipophilicity. All the derivatives studied are more lipophilic than 1. The deshydroxysparsomycin analogues (30-33) showed an interesting phenomenon: increase in hydrophobicity was accompanied by a considerable increase in water solubility. We found that an increase in hydrophobicity of the drug as a result of replacing the SMe group of 1 with larger alkylthio groups causes an increase in the biological activity of the drug. However, not only the hydrophobicity but also shape and size of the substituent are important; in the homologous series 1-9-10-11-12, 21-22-23-24, and 30-31-32-33, highest protein synthesis inhibitory and in vitro cytostatic activity is found with compounds 11, 23, and 32, respectively, and in comparison with the highly active n-butyl compound 10, the isomeric tert-butyl compound 13 is rather inactive. Polar substituents replacing the SMe group, i.e. Cl in 17 and 35, also render the molecule inactive. Substituting the bivalent sulfur atom for a methylene group decreases the drug's activity. This effect can be compensated for by increasing the length of the alkylsulfinyl side chain. The agreement between the results derived from cell-free and "in vivo" tests is good. The assays using ribosomes of bacterial and eukaryotic organisms give similar results although the latter seem to be more sensitive to changes in hydrophobicity of the drug. Our results confirm the presence of a hydrophobic region at the peptidyl transferase center of the ribosome; the interaction of sparsomycin with this region is more pronounced in the eukaryotic particles. The sparsomycin analogues 11, 23, and 30 show the highest antitumor activity against L1210 leukemia in mice, their median T/C values are 386, 330, and 216%, respectively.(ABSTRACT TRUNCATED AT 400 WORDS) 相似文献
995.
Régine Ramdine Anne-Marie Galzin Salomon Z. Langer 《Naunyn-Schmiedeberg's archives of pharmacology》1989,340(4):386-395
Summary In superfused rat hypothalamic slices prelabelled with [3H]-noradrenaline, the 2-adrenoceptor agonist UK 14304 inhibited in a concentration-dependent manner the electrically-evoked release of tritium. This inhibition was antagonized by the 2-adrenoceptor blocking agent idazoxan, which by itself increased the electrically-evoked tritium overflow. Exposure to forskolin, an adenylate cyclase activator, increased the electrically-evoked release of [3H]-noradrenaline. In the presence of forskolin (1 mol/l), both the inhibitory effect of UK 14304 and the increasing effect of idazoxan on the electrically-evoked release of [3H]-noradrenaline were less pronounced than in the absence of the adenylate cyclase activator. Exposure to forskolin and to the phosphodiesterase inhibitor 3-isobutyl-l-methylxanthine shifted to the right the concentration-effect curve for UK 14304 in a similar manner as that observed in the presence of forskolin alone. Exposure to phorbol-12,13-dibutyrate (0.01–10 mol/l), a drug which activates protein kinase C, increased the electrically-evoked release of [3H]-noradrenaline. In the presence of phorbol-12,13-dibutyrate (0.1 and 1 mol/l), the concentration effect curve for UK 14304 on tritium overflow was significantly shifted to the right. The increasing effect of idazoxan on tritium overflow was significantly less pronounced in the presence of 1 mol/l phorbol-12,13-dibutyrate.In superfused rat hypothalamic slices prelabelled with [3H]-5-hydroxytryptamine, the 2-adrenoceptor agonist UK 14304 significantly inhibited the electrically-evoked release of tritium. Exposure to forskolin increased in a concentration-dependent manner [3H]-5-hydroxytryptamine overflow, but did not modify the UK 14304-mediated inhibition. Exposure to 3-isobutyl-1-methylxanthine enhanced the electrically-evoked release of [3H]-5-hydroxytryptamine. In the presence of both forskolin (1 mol/l) and 3-isobutyl-l-methylxanthine (1 mmol/l), the concentration-response curve for UK 14304 was significantly shifted to the right. Exposure to phorbol-12,13-dibutyrate (0.01–10 mol/l) enhanced in a concentration-dependent manner the electrically-evoked overflow of [3H]-5-hydroxytryptamine. In the presence of phorbol-12,13-dibutyrate (0.1 and 1 mol/l), UK 14304 was significantly less potent to inhibit tritium release than in the absence of the protein kinase C activator.It is concluded that both cyclic AMP and phosphoinositide turnover are involved in the modulation of noradrenaline and 5-hydroxytryptamine release by presynaptic 2-adrenoceptors in rat hypothalamic slices. However, these interactions do not represent definitive proof for a cause-effect relationship for the second messengers mediating the 2-adrenoceptor induced inhibition of transmitter release either as autoreceptor or as heteroreceptor.Send offprint requests to S. Z. Langer at the above address 相似文献
996.
997.
To assess the effect of the human atrial natriuretic factor (ANF) in vivo on human veins, a series of investigations was done on the dorsal hand vein of 11 healthy volunteers (ten men, one woman), aged from 25 to 49 years. In the case of intact veins the human ANF effect was evaluated by the "venoconstriction" test; on veins constricted by a reflex sympathetic discharge, the ANF effect was evaluated by the test of "venous reflexes", and on veins constricted with serotonin and angiotensin II by the "preconstriction" test. The results were expressed in venoconstrictive units (VCU). ANF was injected into the vein under study in increasing bolus doses (from 50 pg to 500 ng). The results indicate that this peptide did not affect either intact veins or these constricted by sympathetic discharge. On veins preconstricted with serotonin, ANF had a slight, statistically insignificant effect (848.57 +/- 378.67 VCU 30 sec before, compared to 670.00 +/- 460.25 VCU 30 sec after the injection of 50 pg; n = 7; p greater than 0.05), up to a maximal local dose of 500 ng. The same was true for the vein preconstricted with angiotensin II. It is concluded that the human atrial natriuretic factor has no significant influence on peripheral venous tone in man. 相似文献
998.
Spahn Hildegard Iwakawa Seigo Lin Emil T. Benet Leslie Z. 《Pharmaceutical research》1989,6(2):125-132
The diastereoisomeric glucuronic acid conjugates of R/S-benoxaprofen are the major benoxaprofen metabolites and are found in urine at high concentrations. The conjugates of R- and S-benoxaprofen can be separated directly on a C18 reversed-phase column using a mixture of acetonitrile and tetrabutylammonium hydroxide buffer, pH 2.5 (28:72, v/v), as the mobile phase. The k values of S- and R-benoxaprofen glucuronides are 57.5 and 63.0, respectively. Diluted urine or deproteinized plasma samples were injected without further treatment. With fluorescence detection at 313/365 nm, quantifiable limits of 50 ng equiv./ml were found for the conjugates. The intra- and interday variability was below 12%. Utilizing this analytical procedure it is possible to characterize enantioselective glucuronidation both in vivo and in vitro. For in vitro procedures, apparent rates of formation and the R/S ratio may be substrate (benoxaprofen) and cosubstrate (UDPGA) dependent. Moreover, enantioselective cleavage of the formed benoxaprofen glucuronides by alkaline hydrolysis, hydrolytic enzymes, and acyl migration must be controlled for both in vitro and in vivo studies since R-benoxaprofen glucuronide is degraded faster than the S-diastereomer under certain conditions. 相似文献
999.
Sigmoidin F, a new prenylated flavanone, as well as abyssinone IV and 5,7,4'-trihydroxy-3'-methoxy-5'-(1"-prenyl) flavonone have been isolated from the stem and bark of Erythrina sigmoidea. The structure of 1 has been confirmed by a combination of 1H-nmr and other spectroscopic techniques. 相似文献
1000.