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91.
I van Wijngaarden C G Kruse R van Hes J A van der Heyden M T Tulp 《Journal of medicinal chemistry》1987,30(11):2099-2104
2-Phenylpyrroles were synthesized as conformationally restricted analogues of the substituted benzamide sultopride and the butyrophenones haloperidol and fluanisone. Dopamine antagonistic activity is maintained if the 2-phenylpyrrole side chain is linked to the pharmacophoric N-ethylpyrrolidine moiety of sultopride or to the 4-substituted piperazine moiety of fluanisone but is lost if the 2-phenylpyrrole is combined with the 4-substituted piperidine moiety of haloperidol. The 2-phenylpyrrole analogue 1 of sultopride is in vitro 0.25 and in vivo 3 times as potent as the parent compound. Its binding to the dopamine D-2 receptors is, in analogy to the substituted benzamides, strongly sodium-dependent. The 2-(4-fluorophenyl)pyrrole analogue 5 of fluanisone is superior in vitro as well as in vivo to the corresponding benzamide 7 and the butyrophenone fluanisone. The increase in activity is not only due to a higher affinity for the D-2 receptors but also to an enhanced oral absorption (ratio po/ip = 4.5 vs 40 for the benzamide and 60 for fluanisone). Compound 5 is further characterized by a high selectivity for the D-2 receptors, in contrast to the benzamide and butyrophenone analogues (ratio D-2/alpha 1 = 60, 2.0, and 0.3, respectively). The binding to the D-2 receptors has little dependence on sodium. The 2-phenylpyrrole 5 shares with the benzamide 7 a low potential to induce catalepsy, which is in contrast to haloperidol. So, 5-(4-fluorophenyl)-2-[[4-(2-methoxyphenyl)-1-piperazinyl]methyl]pyrrole (5) is the prototype of a new class of sodium-independent dopamine D-2 antagonists, which may be particularly useful as potential antipsychotics with a low propensity to induce acute extrapyramidal side effects. 相似文献
92.
93.
T. C. M. Brock S. J. H. Crum R. van Wijngaarden B. J. Budde J. Tijink A. Zuppelli P. Leeuwangh 《Archives of environmental contamination and toxicology》1992,23(1):69-84
The fate of the insecticide Dursban® 4E (active ingredient chlorpyrifos) and its effect on crustaceans and insects was studied in indoor experimental freshwater ecosystems that intended to mimick drainage ditches. A single dose (simulating aerial drift) was applied to achieve nominal chlorpyrifos concentrations of 5 or 35 g/L. Two experiments were performed, one in which all model ecosystems were dominated by the macrophyte Elodea nuttallii, and one using systems devoid of macrophytes.In macrophyte-dominated systems, Elodea vegetation adsorbed a large proportion of the dose applied and hampered the mixing of the insecticide in the water (at least up till day 8). Only a small proportion became incorporated in the sediment. In open water systems the insecticide was rapidly mixed in the water, and the sediment played a very significant role as sink for chlorpyrifos. In both Elodea-dominated and open water systems 50% of the dose applied had disappeared on day 8 post-treatment. The rate of disappearance of chlorpyrifos was relatively rapid in water and macrophytes, and relatively slow in the sediment.Of the arthropods in the zooplankton Cladocera were more susceptible than Copepoda. Significant effects (p0.05) on Cladocera occurred relatively late in Elodea-dominated systems (in week 4 post-application) in contrast to open water systems (week 1), which is in accordance with the observed differences in the fate of chlorpyrifos. Daphnia pulex, D. longispina and Simocephalus vetulus recovered in the model ecosystems when chlorpyrifos concentrations were lower than 0.1–0.2 g/L, which is in agreement with results of laboratory protocol tests performed with these cladocerans.Among the macroscopic Arthropoda the apparent order of susceptibility was amphipods > insects > isopods. The isopod Asellus aquaticus was more sensitive to the application of the insecticide than the closely related species Proasellus coxalis. In treated open water systems the latter even increased significantly in numbers. Cage experiments in the model ecosystems performed with several species of Arthropoda indicate that laboratory protocol tests may give a reasonable prediction of short-term direct effects of chlorpyrifos for the same species inhabiting more complex aquatic systems. 相似文献
94.
M C Ansink-Schipper B van Klingeren M H Huikeshoven R K Woudstra M Dessens-Kroon L J van Wijngaarden 《The British journal of venereal diseases》1984,60(3):141-146
We carried out auxanographic typing and plasmid identification on 1380 isolates of penicillinase producing Neisseria gonorrhoeae (PPNG) isolated in the Netherlands in 1982 and found four plasmid patterns and 24 auxotypes with noticeable local or regional variations. Among 756 strains harbouring the 3 X 2 megadalton (Mdal) resistance plasmid ("African" type), with or without the 24 Mdal transfer plasmid, 667 (88%) were non-requiring and inhibited by phenylalanine. This type was endemic in most of the cities or regions we studied. Twenty methionine requiring PPNG strains were found, all harbouring the 3.2 and 24 Mdal plasmid; virtually all of them were isolated or contracted in the region of Groningen. The predominant (443 (71%) auxotype among the 624 PPNG strains containing the 4.5 Mdal plasmid ("Asian" type) (with or without the 24 Mdal plasmid) was proline requiring. This auxotype (with the 4.5 Mdal and 24 Mdal plasmid) caused an outbreak in Amsterdam, and in Groningen replaced the local methionine requiring auxotype which had the 3.2 Mdal and 24 Mdal plasmids. Many auxotypes with the 4.5 Mdal plasmid, and requiring proline only, or proline and isoleucine, circulated in the Hague. Spread of imported strains by prostitution played an important part in the epidemiology of infection with PPNG strains. 相似文献
95.
E. M. G. van Esch S. E. van Wijngaarden H. E. Schaafsma M. J. G. H. Smeets J. P. T. Rhemrev 《Archives of gynecology and obstetrics》2011,283(6):1369-1371
Introduction
A primary fibroid (leiomyoma) arising from both ovaries is rare and can be difficult to diagnose as a result of the low incidence and its indistinctive presentation. A literature review on the diagnostic and therapeutic approach of this rare benign tumour is presented. We describe a case of bilateral primary ovarian fibroid with an unusual presentation to illustrate our recommendations for treatment. 相似文献96.
Identification of differentially expressed genes in a renal cell carcinoma tumor model after endostatin-treatment 总被引:2,自引:0,他引:2
van Wijngaarden J de Rooij K van Beek E Bernsen H Que I van Hinsbergh VW Löwik C 《Laboratory investigation; a journal of technical methods and pathology》2004,84(11):1472-1483
Endostatin is a cleavage product of collagen XVIII that has shown to inhibit tumor-angiogenesis in experimental tumor models. At present, the exact molecular mechanism of action of endostatin is not completely elucidated. In this study, we wanted to identify specific target genes of endostatin. For this purpose, the human renal cell carcinoma RC-9 was subcutaneously implanted in nude mice and treated with endostatin. Tumor growth was inhibited by endostatin after 4 days of treatment. Using immunohistochemistry and the hypoxia marker pimonidazole, we demonstrate disintegration of blood vessels and hypoxia and anoxia as a result of the treatment. Hereafter, we applied the polymerase chain reaction (PCR)-based subtractive suppression hybridization (SSH) method, together with the mirror orientation selection (MOS) technique to identify specifically induced and suppressed genes after endostatin-treatment. We found eight genes to be specifically induced and 11 to be suppressed by the endostatin-treatment. Among other genes, core binding factor a-1/osteoblast-specific factor-2 (cbfa1/osf2) was found to be specifically suppressed by endostatin. Unexpectedly, cbfa1/osf2 was found to be specifically expressed in granulocytes in the tumor, not only in the experimental RC-9 tumor model, but in sections of human breast cancer as well. Since an effect of antiangiogenic therapy on granulocytes has been reported before, this might lead to new insights in the role of granulocytes in antiangiogenic therapy in general. In conclusion, the SSH-PCR implemented with the MOS-technique is a powerful tool to identify differentially expressed genes. Using these techniques, we have identified several target genes of endostatin, of which cbfa1/osf2 was found to be specifically expressed in granulocytes in the tumor. 相似文献
97.
Jennifer L. Kelly Jonathan W. Friedberg Laura M. Calvi Edwin van Wijngaarden Susan G. Fisher 《Cancer causes & control : CCC》2010,21(8):1265-1275
Recent research suggests that ultraviolet radiation exposure (UVRE), our major source of vitamin D, is associated with reduced lymphoma risk. Animal and human studies support an association between vitamin D (vitD) insufficiency and increased risk of some malignancies. We conducted a clinic-based case–control study (140 lymphoma cases, 139 controls; 2002–2005, Rochester, NY) to evaluate UVRE and vitD insufficiency in relation to lymphoma risk. Subjects completed a survey and provided a blood sample. We used multivariable logistic regression to estimate lymphoma risk in relation to past (5–10 years prior) UVRE and current vitD insufficiency (determined by serum 25(OH)D). Possible differences in effect by lymphoma subtype were explored, but statistical power was limited. We confirmed the previously reported decrease in lymphoma risk with past UVRE, specifically sunbathing (>once/week versus never); adjusted odds ratio (ORadj), = 0.28, 95% confidence interval (CI): 0.10–0.79. Current vitD insufficiency was not associated with lymphoma risk (ORadj = 0.89, 95% CI: 0.47–1.72). However, current sunbathing frequency was correlated with measured serum 25(OH)D values. Therefore, while our data do not support an association with current vitD status, development of accurate methods for past vitD assessment to further investigate its role in the association between past UVRE and lymphoma risk is warranted. 相似文献
98.
99.
We review the fundamental changes that are now occurring to the management of neovascular (wet) age‐related macular degeneration (AMD). An improved understanding of the role of vascular endothelial growth factor (VEGF) in the genesis of choroidal neovascular membranes has led to the creation and use of intravitreous anti‐VEGF antibodies (bevacizumab and ranubizumab) and an aptamer (pegaptanib) in the treatment of these lesions. These new intravitreous injections for AMD have supplanted previous treatments in both efficacy and safety and are now the standard of care for neovascular AMD. We discuss the biochemistry of the anti‐VEGF pathway. While there is substantial evidence for the use of ranubizumab and pegaptanib, the intravitreous administration of bevacizumab has not been tested in randomised controlled clinical trials. We review the evidence base for all three agents and the patho‐physiological basis for adverse reactions to intravitreous VEGF blockade. 相似文献
100.
S. C. van Dijk R. T. de Jongh A. W. Enneman A. C. Ham K. M. A. Swart J. P. van Wijngaarden N. L. van der Zwaluw E. M. Brouwer-Brolsma N. M. van Schoor R. A. M. Dhonukshe-Rutten P. Lips C. P. G. M. de Groot Y. M. Smulders H. J. Blom E. J. Feskens J. M. Geleijnse A. H. van den Meiracker F. U. S. Mattace Raso A. G. Uitterlinden M. C. Zillikens N. van der Velde 《Journal of bone and mineral metabolism》2016,34(1):99-108