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51.
The effect of chronic subcutaneous administration of lead acetate was studied in female rabbits. The low-dose group (15 animals) received three times a week 0.10–0.20 g/kg body weight and the high-dose group (15 animals) 0.80–1.20 g/kg. The control group received the vehicle only. Concentrations of lead in blood in the low-dose group increased to ca. 400 g/l after 70 days and in the high-dose group to ca. 900 g/l after 110 days. After 7.5 months eight animals of each group were sacrificed. The remaining rabbits were kept for an additional 4 months without treatment. Blood lead concentrations decreased with a half-time of 60–70 days. During exposure the gain in body weight was lower in the high-dose group than in the control group and the low-dose group. The high-dose group developed slight anaemia and low MCV, MCH and MCHC, and basophilic stippling of erythrocytes. These effects disappeared during recovery. ALAD activity in erythrocytes was very low during exposure in both exposed groups and did not reach control values during recovery. During exposure the concentrations of ZPP and ALA-U increased, but only ALA-U returned to normal during recovery. No other effects of lead on the composition of the urine were observed. No effects were observed on plasma urea and creatinine concentrations. In the highdose group the concentration of ALAD in the liver decreased by 30%. During recovery this effect was no longer present. No effects were seen in cytochrome P-450 content or cytochrome P-450-dependent enzyme activities. Lead was mainly stored in bones, but some also in serveral soft tissues. After recovery the concentrations in soft tissues decreased to a variable degree. In the high-dose group the relative weights of heart and liver increased. These effects disappeared during recovery. At 400 g lead/l blood no adverse effects were observed that did occur at the high dose level.Part 2, dealing with the histopathology and (electron) microscopy of the kidneys is in preparation 相似文献
52.
Edna H. G. Venneker Willem J. Remme MD PhD Diederik C. A. van Hoogenhuyze X. Hanno Krauss G. Louis Bartels Dick A. C. M. Kruijssen Cock J. Storm Dick van Schelven 《Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy》1994,8(2):211-219
Summary Antiischemic effects of 1-blocking agents are based on intrinsic negative inotropic and chronotropic properties. Partial 1-agonistic activity, although useful in preserving cardiac function, may counteract such antischemic properties by modulating the intrinsic negative cardiac effects of beta-blockade. To investigate the acute hemodynamic and antiischemic profile of epanolol, a cardioselective 1-antagonist and partial agonist, 20 patients with left coronary artery disease underwent two incremental atrial pacing tests, 45 minutes before (APST I) and 15 minutes after (APST II) 4 mg intravenous epanolol, administered over 5 minutes. Additional measurements were carried out at 1, 3, 5, 10, and 15 minutes after epanolol, at basal and fixed heart rates. Epanolol immediately reduced heart rate with a maximum of 10% at 15 minutes and decreased contractility (Vmax) by 7% (both p<.05), whereas cardiac output fell temporarily by 9% (p<.05). Other hemodynamic parameters did not change, except for a significant 11% reduction in myocardial oxygen demand. Despite comparable pacing conditions, both the double product and contractility decreased significantly less during APST II, resulting in a 17% lower myocardial oxygen consumption (p<.05). Myocardial ischemia was markedly reduced, indicated by normalization of lactate metabolism [lactate extraction 16±7% vs. –7±8% (APST I)], less ST depression (21%), and modulation of LV end-diastolic pressure postpacing (all p<.05 vs. APST I), whereas angina was absent or less in 14 patients. None of the patients reported an adverse effect. Thus, under resting conditions intravenous epanolol induces moderate, short-lasting negative chronotropic and inotropic effects, but does not alter cardiac pump function or vascular resistance, reflecting its additional 1-agonistic properties. Alternatively, during pacing it still reduces ischemia through negative inotropic effects and diminishes myocardial oxygen demand, reflecting its 1-antagonistic profile. 相似文献
53.
Alexander Sparreboom Manon T. Huizing Jan J. B. Boesen Willem J. Nooijen Olaf van Tellingen Jos H. Beijnen 《Cancer chemotherapy and pharmacology》1995,36(4):299-304
Three metabolites of the cytotoxic drug paclitaxel (Taxol) were isolated and purified from the feces of cancer patients receiving the agent as an intravenous infusion. The procedures involved sample homogenization in water followed by liquid-liquid extraction with diethyl ether and high-performance liquid chromatography (HPLC). Approximately 1–3.5 mg of each metabolite was obtained from 100 g of feces. As judged from the chromatographic traces of analytical HPLC with ultraviolet (UV) detection at 227 nm, the purity of each compound was >97%. On-line photodiode-array detection demonstrated that the UV spectrum of the isolated compounds closely resembles that of the parent drug. Mass spectrometry provided evidence that these metabolites are mono- and dihydroxy-substituted derivatives, namely, 6-hydroxypaclitaxel, 3-p-hydroxypaclitaxel, and 6,3-p-dihydroxypaclitaxel. The two 6-hydroxy-substituted metabolites were shown to have lost their cytotoxicity in in vitro clonogenic assays using the A2780 human ovarian carcinoma and the CC531 rat colon-carcinoma tumor cell lines. In addition, the metabolites showed reduced myelotoxic effects as compared with paclitaxel in an in vitro hemopoietic progenitor toxicity assay. Our procedure for the isolation and purification of paclitaxel metabolites in milligram quantities should be useful for testing the biological activities of these compounds and for the preparation of calibration standards essential for pharmockinetics studies. 相似文献
54.
55.
Hugo J. Van Staveren Hans P. A. Marijnissen Maurice C. G. Aalders Willem M. Star 《Lasers in medical science》1995,10(2):137-147
Spherical isotropic fibre optic light diffusers are used in photodynamic therapy either as a light source or as a light detector. The construction of light diffusers using different materials is described, viz. an optical method involving local polymerization of a dental fissure sealant, which is referred to as the Henderson method, and a second method using plastic or ceramic pre-fabricated spheres. Quality tests necessary for reliable clinical use are presented for the mechanical strength, output power and isotropy. The maximum pull-off force and blow-off output power for the different kinds of diffusers were determined. The calibration procedures are given for measurement of the output power and wavelength of the light emitted by a diffuser and for measurement of the fluence rate by a light-detecting diffuser, using a compact integrating sphere device. With all types of diffusers described, an isotropy can be obtained of better than ± 20% measured over a 320° angle for spheres as small as 1 mm. Larger ceramic diffusers are particularly suitable for delivering high output powers. A 3-mm-diameter ceramic diffuser mounted on a 600-m-core fibre can emit up to 5 W of continuous wave (CW) visible light in air. Diffusers used for light detection can measure the light fluence rate in tissue with 15% accuracy or better if calibration factors are determined for each individual probe. 相似文献
56.
Ladriere L Verbruggen I Grue-Sørensen G Björkling F Willem R Malaisse WJ 《International journal of molecular medicine》1999,3(3):285-289
The metabolism of [1,3-(13)C]glycerol-1,2,3-tris(methylsuccinate) and glycerol-1,2,3-tris(methyl[2,3-(13)C] succinate) was examined in hepatocytes prepared from hereditarily diabetic Goto-Kakizaki rats. Over 120 min incubation in the presence of one of the two (13)C-labelled esters (2.5 mM), the output of (13)C-enriched glucose averaged 57.1 +/- 18.5 and 54.1 +/- 22.7 nmol per 10(6) cells, when expressed as [1,3-(13)C]glycerol and [2,3-(13)C] succinate equivalent, respectively. In the case of [1,3-(13)C]glycerol-1,2,3-tris(methyl-succinate), the molecules of glucose were symmetrically labelled. In the case of glycerol-1,2,3-tris(methyl[2,3-(13)C] succinate), however, both the single-labelled and double-labelled isotopomers of glucose contained more (13)C atoms in their C(6)-C(5)-C(4) than C(1)-C(2)-C(3) moiety. These findings indicate that glycerol-1,2,3-tris(methylsuccinate), recently proposed as a novel insulinotropic tool for the treatment of non-insulin-dependent diabetes mellitus, is efficiently metabolized in hepatocytes from diabetic rats, the high rate of gluconeogenesis coinciding with channelling of D-glyceraldehyde-3-phosphate between glyceraldehyde-3-phosphate dehydrogenase and phosphofructoaldolase. 相似文献
57.
58.
Leonie J. M. Rijks Gerard J. Boer Erik Endert Kora de Bruin Jan C. van den Bos Peter A. P. M. van Doremalen Willem G. E. J. Schoonen Anton G. M. Janssen Eric A. van Royen 《European journal of nuclear medicine and molecular imaging》1996,23(3):295-307
We studied the potential of both stereoisomers of 17-[123I]iodovinyloestradiol (E- andZ-[123I]IVE) and of 11-methoxy-17-[123I]iodovinyloestradiol (E-andZ-[123I]MIVE) as suitable radioligands for the imaging of oestrogen receptor(ER)-positive human breast tumours. The 17-[123I]iodovinyloestradiols were prepared stereospecifically by oxidative radio-iododestannylation of the corresponding 17-tri-n-butylstannylvi-nyloestradiol precursors. Competitive binding studies were performed in order to determine the relative binding affinity (RBA) of the unlabelled 17-iodovinyloes-tradiols for the ER in both human MCF-7 breast tumour cells and rat uterine tissue, compared with that of diethylstilboestrol (DES). Target tissue uptake, retention and uptake selectivity of their123I-labelled analogues were studied in immature female rats. All four 17-iodovi-nyloestradiols showed high affinity for the ER in human MCF-7 cells, as well as rat uterus. Their RBA for the ER showed the following order of decreasing potency: RBA of DES >Z-IVE >Z-MIVE >E-MIVE E-IVE. Neither of these 17-iodovinyloestradiols showed any significant binding to the sex hormone binding globulin in human plasma. The biodistribution studies showed ER-mediated uptake in the uterus, ovaries and pituitary, that ofE- andZ-[123I]MIVE being higher than that ofE- andZ-[123I]IVE. High target-to-non-target tissue uptake ratios, especially at longer periods after injection (up to 24 h), were exhibited by both isomers of [123I]MIVE. The uterus-to-blood uptake ratio was higher forE-[123I]MIVE. However, the uterus-to-fat uptake ratio appeared to be higher for theZ-isomer of [123I]MIVE, especially at 24 h after injection. Metabolic properties and temperature effects, which play a more important role in vivo, probably cause the discrepancies seen between in vitro and in vivo binding results. On the basis of their in vitro binding properties and in vivo distribution characteristics we conclude thatE- andZ-[123I]MIVE could be suitable radioligands for the diagnostic imaging of ER in human breast cancer. Therefore, further studies with these radioligands in mature normal and tumour-bearing rats are warranted. 相似文献
59.
Summary The creatine kinase (CK) activity of the serum of 33 male and 24 female patients with tibial shaft fractures has been assayed. In 40 of the 57 patients the CK level surpassed the maximal normal limit of 1.7 tkat/l. Patients with fractures due to direct violence had significantly higher levels than those with fractures due to indirect violence. When the fracture was displaced the CK level was more often abnormal than when there was no displacement. Patients with extensive swelling of the injured leg had significantly higher levels than patients with minor or no swelling. CK determinations could be used to quantify muscle injury.
Zusammenfassung Die Serum-Kreatinkinase (CK)-Werte von 33 männlichen and 24 weiblichen Patienten mit einer Tibiadiaphysenfraktur wurden gemessen. Bei 40 von 57 Patienten lag der Serum-CK-Spiegel über dem oberen Normalwert von 1,7 kat/l. Bei Patienten mit Frakturen, verursacht durch ein direktes Trauma, wurden signifikant höhere Serum-CK-Werte gemessen als bei Patienten mit Frakturen, entstanden durch ein indirektes Trauma. Der Serum-CK-Spiegel war öfter erhöht bei Patienten mit einer Fraktur mit Fehlstellung, verglichen mit Patienten mit einer Fraktur ohne Fehlstellung. Patienten mit einer außergewöhnlichen Schwellung des geschädigten Beines hatten signifikant höhere Serum-CK-Werte als Patienten mit geringer oder keiner Schwellung. Die Serum-CK kann dazu benutzt werden, den Muskelschaden quantitativ zu beurteilen.相似文献
60.
David A. Wright Willem H. Roosenburg 《Archives of environmental contamination and toxicology》1982,11(4):491-495
The toxicity of four trimethyltin concentrations to stage I zoeae of the fiddler crab,Uca pugilator, was tested at temperatures of 10°C, 20°C and 28°C and salinities of 10, 20 and 30. Stepwise multiple regression of the probit of mortality data produced a formula from which productive response surfaces were generated. 24 hr LC 50's in 30 salinity at 10°C was 12 ppm, at 20°C 3.35 ppm and 0.61 ppm at 28°C. Corresponding 48 hr LC 50's were about one-tenth of these values. An increase in temperature and a decrease in salinity sharply increased trimethyltin toxicity in fiddler crab zoeae.Contribution No. 1226, Center for Environmental and Estuarine Studies, University of Maryland 相似文献