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G H Deckers J H de Graaf H J Kloosterboer H J Loozen 《The Journal of steroid biochemistry and molecular biology》1992,42(7):705-712
Org 30850 (Ac-D-pClPhe1,2,D-Bal3,D-Lys6,D-Ala10-LHRH) is a novel LHRH antagonist, which is being developed for the treatment of hormone-dependent disorders. The activities of this compound with respect to its endocrinological properties and side-effects were tested in rats and the results were compared with one of the first LHRH antagonists: Ac-D-pClPhe1,2,D-Trp3,D-Arg6,D-Ala10-LHRH (Org 30276). A single subcutaneous (s.c.) dose of 0.3 micrograms/kg Org 30850 administered to rats in pro-estrus gave inhibition of ovulation in approx. 50% of the rats, whereas Org 30276 was approx. 4 times less potent. The effect of a single s.c. injection of Org 30850 on testosterone levels in young adult male rats was also studied. The administration of 250 micrograms/kg or higher of Org 30850 induced a significant decrease in testosterone levels after 3 h, this effect lasted for at least 48 h. Treatment of female rats for 14 days with a daily dose of 12 micrograms/kg Org 30850 decreased statistically significantly uterine and ovarian weights. At a daily dose of 50 micrograms/kg Org 30850 completely suppressed estrous cycles and significantly decreased estradiol and FSH serum levels. The LH levels were below the detection level in both control and treated animals on the (expected) second day of di-estrus. Treatment of male rats for 14 days (25-200 micrograms/kg) resulted in a dose-dependent reduction of the gonads, accessory sex organs, testosterone levels and gonadotrophins. The decrease in gonadal function in both sexes was reversible since the females proved to be as fertile as the controls 6 weeks after the last treatment and an almost complete recovery of the weight of testes, seminal vesicles and ventral prostate was observed in the males 4 weeks after cessation of treatment. In contrast to Org 30276, Org 30850 exerted very slight irritation at the site of injection and no edematous reactions in the extremities at a daily dose of up to 8 mg/kg in male rats. It is concluded that Org 30850 is a very potent LHRH antagonist without edematous reactions and with a more favourable therapeutic index than Org 30276. 相似文献
3.
Identification of a large family of genes for putative chemoreceptor proteins in an ordered library of the Desulfovibrio vulgaris Hildenborough genome. 总被引:3,自引:2,他引:1 下载免费PDF全文
A library of 879 recombinant lambda phages, constructed for the genome of Desulfovibrio vulgaris Hildenborough, has been ordered by restriction fingerprinting. Restriction endonuclease HinfI digestion patterns were entered into a data base and sorted into 87 overlapping groups (contigs), with 19 clones remaining unattached. Eight of ten cloned genes of D. vulgaris, including dcrA, which encodes a transmembrane methyl-accepting protein, were assigned to contigs. Probing of a filter containing the lambda DNAs of the library with the labeled, conserved 3' end of the dcrA gene indicated hybridization to 54 clones distributed over multiple contigs. The presence of 11 additional dcr genes (dcrB to dcrL) was confirmed by direct cycled dideoxy sequencing of positive lambda clones. Since the ordered library provides only partial coverage of the D. vulgaris Hildenborough genome, we estimate that the dcr gene family has 16 members spread throughout the genome, making it the second largest gene family found in prokaryotes. 相似文献
4.
Dimitra Ioannidou Niko Heeren Guido Sonnemann Guillaume Habert 《Journal of Industrial Ecology》2019,23(4):751-766
In recent literature, the concept of criticality aspires to provide a multifaceted risk assessment of resource supply shortage. However, most existing methodologies for the criticality assessment of raw materials are restricted to a fixed temporal and spatial reference system. They provide a snapshot in time of the equilibrium between supply and demand/economic importance and do not account for temporal changes of their indicators. The static character of criticality assessments limits the use of criticality methodologies to short‐term policy making of raw materials. In the current paper, we argue for an enhancement of the criticality framework to account for three key dynamic characteristics, namely changes of social, technical, and economic features; consideration of the spatial dimension in site‐specific assessments; and impact of changing governance frameworks. We illustrate how these issues were addressed in studies outside of the field of criticality and identify the dynamic parameters that influence resource supply and demand based on a review of studies that belong to the general field of resource supply and demand. The parameters are grouped in seven categories: extraction, social, economic, technical, policy, market dynamics, and environmental. We explore how these parameters were considered in the reviewed studies and propose ways and specific examples of addressing the dynamic effects in the criticality indicators. Furthermore, we discuss the current work on future scenarios to provide reference points for indicator benchmarks. The insights and guidelines derived from the review and our recommendations for future research set the foundations for an enhanced dynamic and site‐specific criticality assessment framework. 相似文献
5.
Adipose tissue fibrosis,hypertrophy, and hyperplasia: Correlations with diabetes in human obesity 下载免费PDF全文
Lindsey A. Muir Christopher K. Neeley Kevin A. Meyer Nicki A. Baker Alice M. Brosius Alexandra R. Washabaugh Oliver A. Varban Jonathan F. Finks Brian F. Zamarron Carmen G. Flesher Joshua S. Chang Jennifer B. DelProposto Lynn Geletka Gabriel Martinez‐Santibanez Niko Kaciroti Carey N. Lumeng Robert W. O'Rourke 《Obesity (Silver Spring, Md.)》2016,24(3):597-605
6.
Simone?RiehlEmail author Marion?Benz Nicholas?J.?Conard Hojjat?Darabi Katleen?Deckers Hassan?Fazeli?Nashli Mohsen?Zeidi-Kulehparcheh 《Vegetation History and Archaeobotany》2012,21(2):95-106
The beginnings of agriculture throughout the Fertile Crescent are still not completely understood, particularly at the eastern end of the Fertile Crescent in the area of modern Iran. Archaeobotanical samples from Epipalaeolithic/PPNA Körtik Tepe in southeastern Turkey and from the Pre-Pottery Neolithic sites of Chogha Golan and East Chia Sabz in south western Iran were studied in order to define the status of cultivation at these sites. Preliminary results show the presence of abundant wild progenitor species of crops at the Iranian sites before 10600 cal. b.p., and very few wild progenitor species at Körtik Tepe dated to 11700–11250 cal. b.p. The Iranian sites also indicate size increase of wild barley grain across a sequence of 400 years through either cultivation or changing moisture conditions. 相似文献
7.
Roope J. Huttunen Tomás C. O'Riordan Pirkko L. Härkönen Juhani T. Soini Niko J. Meltola Pekka E. Hänninen Aleksi E. Soini 《Luminescence》2007,22(3):163-170
A method is introduced for quantitative detection of cell surface protein expression. The method is based on immunocytochemistry, the use of long decay time europium(III) chelate and platinum(II) porphyrin labels, and detection of photoluminescence emission from adhered cells by time-resolved fluorimetry. After immunocytochemistry, the assay wells are evaporated to dryness and measured in the dry state. This protocol allows repeated and postponed analysis and microscopy imaging. In order to investigate the performance of the method, we chose expression of intercellular adhesion molecule-1 (ICAM-1) of endothelial cell line EAhy926 as a research target. The expression of ICAM-1 on the cells was enhanced by introduction of a cytokine, tumour necrosis factor-alpha (TNFalpha). The method gave signal:background ratios (S:B) of 20 and 9 for europium and platinum labels, respectively, whereas prompt fluorescent FITC label gave a S:B of 3. Screening window coefficients (=Z'-factor) were >0.5 for all the three labels, thus indicating a score for an excellent screening assay. In conclusion, the method appears to be an appropriate choice for protein expression analysis, both in high-throughput screening applications, and for detailed sample investigation by fluorescent microscopy imaging. 相似文献
8.
Polar transport of the signaling molecule auxin is critical for plant development and depends on both the polar distribution of auxin efflux carriers, which pump auxin out of the cell and the alignment of these polarized cells. Two papers in this issue of Cell (Michniewicz et al., 2007; Jaillais et al., 2007) address how polar transport of these carriers occurs and describe the endosomal pathways involved. 相似文献
9.
Changes in antioxidant status of heart muscle tissue in experimental diabetes in rabbits 总被引:2,自引:0,他引:2
The present study was designed to evaluate the oxidative stress-related parameters in alloxan-induced diabetes in rabbits. After 3, 6, 12 and 24 weeks of hyperglycaemia the enzymatic and non-enzymatic factors were measured in heart tissue of diabetic and control groups. Superoxide dismutase and glutathione peroxidase activities and the contents of total sulfhydryl compounds significantly increased at all time intervals. Catalase activity increased initially (after 3 and 6 weeks), decreased after 12 weeks and increased again at the 24th week of the experiment. Glutathione reductase activity increased initially (at 3rd week), decreased below control level after 6 and 12 weeks, then increased again. Ascorbic acid concentration decreased after 3 and 6 weeks, and increased at the 12th and 24th weeks. The level of lipid peroxidation products was reduced after 3, 6 and 12 weeks of the experiment. After 24 weeks it was significantly elevated. These data suggest that hyperglycaemia induces oxidative stress in the heart but the defense mechanisms in the heart tissue are fairly efficacious against oxidative injury. 相似文献
10.
Brecht Devleesschauwer Juanita A. Haagsma Frederick J. Angulo David C. Bellinger Dana Cole D?rte D?pfer Aamir Fazil Eric M. Fèvre Herman J. Gibb Tine Hald Martyn D. Kirk Robin J. Lake Charline Maertens de Noordhout Colin D. Mathers Scott A. McDonald Sara M. Pires Niko Speybroeck M. Kate Thomas Paul R. Torgerson Felicia Wu Arie H. Havelaar Nicolas Praet 《PloS one》2015,10(12)