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排序方式: 共有1337条查询结果,搜索用时 15 毫秒
11.
Matthias Lngin Bruno Reichart Stig Steen Trygve Sjberg Audrius Paskevicius Qiuming Liao Guangqi Qin Maren Mokelke Tanja Mayr Julia Radan Lara Issl Ines Buttgereit Jiawei Ying Ann Kathrin Fresch Alessandro Panelli Stefanie Egerer Andrea Bhr Barbara Kessler Anastasia Milusev Riccardo Sfriso Robert Rieben David Ayares Peter J. Murray Reinhard Ellgass Christoph Walz Nikolai Klymiuk Eckhard Wolf Jan‐Michael Abicht Paolo Brenner 《Xenotransplantation》2021,28(1):e12636
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We compared the effect on intraocular pressure (IOP) of maximal doses of a topical carbonic anhydrase inhibitor (CAI) at acidic and alkaline pH where it is maximally effective with full systemic CA inhibition in ocular normotensive New Zealand Albino rabbits. Tonometric IOP levels were measured hourly during 3 hour control period. Topical MK-417 (pKa 5.8, 8.3), a close congener of MK-507 (Dorzolamide) was given as a 1.4% solution at pH 4.5 (n=6) and pH 9.2 (n=6). MK-417 was instilled to the left eye with the right eye used as an untreated control. One hour later methazolamide was given intravenously at 10 mg/kg, a dose known to give full inhibition of the enzyme. Control IOP (mm Hg) was 19.12+/-0.50. One hour following MK-417, the left eye IOP was 13.40 +/-0.70 (pH 4.5) and 13.25+/-0.70 (pH 9.2). The right eye pressure was unchanged. Methazolamide injection at this time gave no further drop in the left eye IOP at either pH. IOP in the right eye fell to 14.00+/-0.70 so that 2 hours after methazolamide injection, the 2 eyes had the same pressure. In conclusion, topical CAI in sufficient dose and correct pH yields IOP lowering equivalent to a maximally effective dose of systemic CAI in rabbits. 相似文献
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The role of contextual versus discrete drug-associated cues in promoting the induction of psychomotor sensitization to intravenous amphetamine 总被引:7,自引:0,他引:7
The environmental context in which psychostimulant drugs are administered can have a large effect on both their acute psychomotor activating effects and their ability to induce the psychomotor sensitization associated with repeated drug administration. For example, the acute effects of amphetamine and the development of psychomotor sensitization to amphetamine and cocaine are enhanced when they are administered in a distinct and relatively novel test environment, relative to when they are given in the home cage, in the absence of any environmental stimuli predictive of drug administration. The experiments reported here were designed to further examine this phenomenon and to test the hypothesis that the ability of a distinct context to promote robust psychomotor sensitization is due to its ability to reliably signal (cue) drug administration. Specifically, we compared the ability of contextual cues (a distinct test environment) and discrete cues (light, tone and/or odor), which both reliably predict drug administration, to promote the induction of sensitization. The psychomotor stimulant effects (rotational behavior) of repeated intravenous infusions of 0. 5 mg/kg amphetamine were assessed in rats for whom drug treatments were signaled either: (1) by placement into a distinct test environment; (2) by presentation of discrete cues; or (3) rats for whom drug treatments were given in the home environment in the absence of any environmental cues. Amphetamine produced robust sensitization when given in association with placement into a distinct test environment. The same treatment failed to produce sensitization when the drug was given unsignaled in the animal's home cage. Most importantly, signaling drug administration by presenting discrete cues was not sufficient to promote the robust sensitization seen when treatments were given in a distinct test environment. These results confirm that the induction of psychomotor sensitization can be powerfully modulated by environmental context and further establish that, although contextual stimuli associated with a distinct test environment promote robust sensitization, discrete cues that merely predict drug administration do not have this property. Possible reasons for the difference in the ability of contextual versus discrete environmental cues to promote sensitization are discussed. 相似文献
14.
Emily Kuhlmann Pauline Scharli Maren Schick Beate Ditzen Laila Langer Thomas Strowitzki Tewes Wischmann Ruben-J. Kuon 《Geburtshilfe und Frauenheilkunde》2023,83(1):88
Introduction Recurrent pregnancy loss is usually associated with significant psychological distress for both partners of the couple. It may act as a traumatic experience resulting in a posttraumatic stress disorder. The object of this study is to examine the posttraumatic impact of recurrent pregnancy loss on men and women and their interdependencies. Methods Cross-sectional study. All couples referred to the special unit for recurrent pregnancy loss between March 2019 and October 2020 were asked to participate with a sample size of 105 couples and 17 women. They were invited to complete a questionnaire package estimating the prevalence of posttraumatic stress, with anxiety, depression, lack of social support and dysfunctional coping strategies as contributing risk factors. Couple data were analysed with the Actor Partner Interdependence Model, taking the couple as a dyad. Results The response rate was 82.3 percent, with posttraumatic stress being measured in 13.7% of the women versus 3.9% of the men (p = 0.017). For women, number of curettages, controlled for the number of losses, correlated with the severity of posttraumatic stress (p < 0.05). Higher levels of anxiety, depression and lack of social support in women correlated positively with posttraumatic stress in their partners. The men’s coping strategy “trivialization and wishful thinking” as well as “avoidance” correlated with more severe posttraumatic stress in the female partners (both p < 0.05). Conclusion The posttraumatic risks within a couple with recurrent pregnancy loss are interdependent. Recurrent pregnancy loss clinics should assess posttraumatic risks of both partners in their routine diagnostic process. 相似文献
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16.
Julian Seidel Georg Schmitt Maren Hoffmann Dieter Jendrossek Oliver Einsle 《Proceedings of the National Academy of Sciences of the United States of America》2013,110(34):13833-13838
Rubber oxygenase A (RoxA) is one of only two known enzymes able to catalyze the oxidative cleavage of latex for biodegradation. RoxA acts as a processive dioxygenase to yield the predominant product 12-oxo-4,8-dimethyl-trideca-4,8-diene-1-al (ODTD), a tri-isoprene unit. Here we present a structural analysis of RoxA from Xanthomonas sp. strain 35Y at a resolution of 1.8 Å. The enzyme is a 75-kDa diheme c-type cytochrome with an unusually low degree of secondary structure. Analysis of the heme group arrangement and peptide chain topology of RoxA confirmed a distant kinship with diheme peroxidases of the CcpA family, but the proteins are functionally distinct, and the extracellular RoxA has evolved to have twice the molecular mass by successively accumulating extensions of peripheral loops. RoxA incorporates both oxygen atoms of its cosubstrate dioxygen into the rubber cleavage product ODTD, and we show that RoxA is isolated with O2 stably bound to the active site heme iron. Activation and cleavage of O2 require binding of polyisoprene, and thus the substrate needs to use hydrophobic access channels to reach the deeply buried active site of RoxA. The location and nature of these channels support a processive mechanism of latex cleavage. 相似文献
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Richter CM Godes M Wagner C Maser-Gluth C Herzfeld S Dorn M Priem F Slowinski T Bauer C Schneider W Neumayer HH Kurtz A Hocher B 《Journal of hypertension》2004,22(1):191-198
BACKGROUND: It has been shown that the macula densa participates in the regulation of increased renin expression in two-kidney one-clip (2K1C) renovascular hypertension. Prostaglandins might be one of the mediators of macula densa function, because the cyclooxygenase-2 (COX-2), one of the rate-limiting enzymes of the prostaglandin pathway, is upregulated in 2K1C renovascular hypertensive rats. We tested the effect of chronic COX-2 inhibition on blood pressure, urinary aldosterone excretion and kidney morphology, as well as kidney function. METHODS: Four groups were established: two groups of 2K1C renovascular hypertensive rats treated with the specific COX-2 inhibitor Celecoxib (cele) (15 mg/kg per day) or placebo immediately after operation, and two sham-operated control groups fed with Celecoxib or placebo. RESULTS: Long-term COX-2 inhibition in 2K1C renovascular hypertensive rats did not alter blood pressure at any point of time. Urinary aldosterone excretion was elevated by clipping the renal artery (2K1C, 8.1 +/- 1.9, versus controls, 3.6 +/- 0.5 ng/24 h; P = 0.05) but was not influenced by treatment with Celecoxib. Also, Celecoxib treatment did not alter glomerular filtration rate (GFR), serum sodium, serum creatinine, serum urea or proteinuria in 2K1C renovascular hypertensive rats. Interstitial fibrosis of the left clipped kidney was markedly reduced (2K1C, 6.19 +/- 0.83% versus 2K1C + cele 3.00 +/- 0.68% of total area; P = 0.012), whereas the interstitial fibrosis of the non-clipped kidney or the glomerulosclerosis of both kidneys were not affected by Celecoxib treatment. CONCLUSIONS: Celecoxib reduces the interstitial fibrosis of the clipped kidney. Blood pressure, urinary aldosterone excretion or whole kidney function were not affected in renal hypertensive rats. 相似文献
20.
Heparin-induced thrombocytopenia (HIT) is a serious complication of heparin therapy. Limited data are available regarding repeat HIT antibody testing after an initial negative test. We conducted a retrospective study to determine the utility of repeat testing. Heparin antibodies were detected using the GTI-PF4 enzyme-linked immunoabsorbent assay, ELISA (GTI Diagnostics, Waukesha, WI). Patients (n = 137) were assigned to one of three groups based upon the initial negative test optical density (OD) range of low = 0-0.132, medium = 0.133-0.267, and high = 0.268-0.399. A pretest clinical score was retrospectively determined using the "4T's" (Thrombocytopenia, Timing of platelet fall, Thrombosis, and the absence of oTher causes of thrombocytopenia). A subsequent positive ELISA was found in 16% (22/137) of patients who underwent repeat testing. Most of these patients had a low pretest clinical score (62%). Four patients had an interval change in the pretest score between the initial negative and subsequent positive tests. Only these four patients developed HIT with thrombosis (HITT). Eighty percent of patients with a high initial negative test OD value had a positive ELISA on repeat testing; however, the initial negative test OD value could not predict whether a patient developed HITT. In contrast, an increase in the pretest clinical probability between initial and repeat testing better predicted HITT. Consecutive repeat ELISA testing for heparin antibodies may be warranted in patients with an increase in their pretest clinical score after an initial negative test as an adjunct to confirm the diagnosis of HIT. 相似文献