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排序方式: 共有1574条查询结果,搜索用时 265 毫秒
41.
42.
Agnieszka Zagrska Anna Partyka Adam Bucki Marcin Koaczkowski Magdalena Jastrzbska‐Wisek Anna Czopek Agata Siwek Monika Guch‐Lutwin Marek Bednarski Marek Bajda Jakub Joczyk Kamil Piska Paulina Koczurkiewicz Anna Wesoowska Maciej Pawowski 《Chemical biology & drug design》2019,93(4):511-521
A series of 2‐pyrimidinyl‐piperazinyl‐alkyl derivatives of 1H‐imidazo[2,1‐f]purine‐2,4(3H,8H)‐dione has been synthesized in an attempt to discover a new class of psychotropic agents. Compounds were evaluated for their in vitro affinity for serotonin 5‐HT1A, 5‐HT7, and phosphodiesterases PDE4 and PDE10. The most potent compound 2‐pyrimidinyl‐1‐piperazinyl‐butyl‐imidazo[2,1‐f]purine‐2,4‐dione ( 4b ) behaved as strong and selective antagonist of 5‐HT1A. Molecular modeling studies revealed differences in binding mode between compound 4b and buspirone, which might reflect variation of the ligands’ affinity and potency in the 5‐HT1A receptor. Compound 4b in silico models demonstrated drug‐likeness properties and, contrary to buspirone, showed a metabolic stability in mouse liver microsomes system. Experimentally obtained value of apparent permeability coefficient Papp for 4b in parallel artificial permeability assay indicates the possibility of binding weakly to plasma proteins and high intestinal absorption fraction. Evaluation of the antidepressant‐ and anxiolytic‐like activities of 4b revealed both activities at the same dose of 1.25 mg/kg and seemed to be specific. The antidepressant and/or anxiolytic properties of 4b may be related to its first‐pass effect. 相似文献
43.
Serkan ?zkul Akif Turna Ahmet Demirkaya Burcu Aksoy Kamil Kaynak 《Journal of thoracic disease》2014,6(12):1731-1735
Background
Chemical pleurodesis can be palliative for recurrent, symptomatic pleural effusions in patients who are not candidate for a thoracic surgical procedure. We hypothesized that effective pleurodesis could be accomplished with a rapid method of pleurodesis as effective as the standard method.Methods
A prospective randomized ‘non-inferiority’ trial was conducted in 96 patients with malignant pleural effusion (MPE) who are not potentially curable and/or not amenable to any other surgical intervention. They were randomly allocated to group 1 (rapid pleurodesis) and to group 2 (standard protocol). In group 1, following complete fluid evacuation, talc slurry was instilled into the pleural space. This was accomplished within 2 h of thoracic catheter insertion, unless the drained fluid was more than 1,500 mL. After clamping the tube for 30 min, the pleural space was drained for 1 h, after which the thoracic catheter was removed. In group 2, talc-slurry was administered when the daily drainage was lower than 300 mL/day.Results
No-complication developed due to talc-slurry in two groups. Complete or partial response was achieved in 35 (87.5%) and 33 (84.6%) patients in group 1 and group 2 respectively (P=0.670). The mean drainage time was 40.7 and 165.2 h in group 1 and group 2 respectively (P<0.001).Conclusions
Rapid pleurodesis with talc slurry is safe and effective and it can be performed in an outpatient basis. 相似文献44.
45.
46.
Dietrich E. Lorke Syed M. Nurulain Mohamed Y. Hasan Kamil Ku
a Georg A. Petroianu 《Journal of applied toxicology : JAT》2019,39(11):1506-1515
Organophosphates, useful agents as pesticides, also represent a serious danger due to their high acute toxicity. There is indication that oximes, when administered before organophosphate exposure, can protect from these toxic effects. We have tested at equitoxic dosage (25% of LD01) the prophylactic efficacy of five experimental (K‐48, K‐53, K‐74, K‐75, K‐203) and two established oximes (pralidoxime and obidoxime) to protect from mortality induced by the organophosphate paraoxon. Mortalities were quantified by Cox analysis and compared with those observed after pretreatment with a strong acetylcholinesterase inhibitor (10‐methylacridine) and after the FDA‐approved pretreatment compound pyridostigmine. All nine tested substances statistically significantly reduced paraoxon‐induced mortality. Best protection was conferred by the experimental oxime K‐48, reducing the relative risk of death (RR) to 0.10, which was statistically significantly superior to pyridostigmine (RR = 0.31). The other oximes reduced the RR to 0.13 (obidoxime), 0.20 (K‐203), 0.21 (K‐74), 0.24 (K‐75) and 0.26 (pralidoxime), which were significantly more efficacious than 10‐methylacridine (RR = 0.65). These data support the hypothesis that protective efficacy is not primarily due to cholinesterase inhibition and indicate that the tested experimental oximes may be considered promising alternatives to the established pretreatment compound pyridostigmine. 相似文献
47.
Lakshmanan V Rhee KY Wang W Yu Y Khafizov K Fiser A Wu P Ndir O Mboup S Ndiaye D Daily JP 《The Journal of infectious diseases》2012,206(2):238-248
Metabolomics offers a powerful means to investigate human malaria parasite biology and host-parasite interactions at the biochemical level, and to discover novel therapeutic targets and biomarkers of infection. Here, we used an approach based on liquid chromatography and mass spectrometry to perform an untargeted metabolomic analysis of metabolite extracts from Plasmodium falciparum-infected and uninfected patient plasma samples, and from an enriched population of in vitro cultured P. falciparum-infected and uninfected erythrocytes. Statistical modeling robustly segregated infected and uninfected samples based on metabolite species with significantly different abundances. Metabolites of the α-linolenic acid (ALA) pathway, known to exist in plants but not known to exist in P. falciparum until now, were enriched in infected plasma and erythrocyte samples. In vitro labeling with (13)C-ALA showed evidence of plant-like ALA pathway intermediates in P. falciparum. Ortholog searches using ALA pathway enzyme sequences from 8 available plant genomes identified several genes in the P. falciparum genome that were predicted to potentially encode the corresponding enzymes in the hitherto unannotated P. falciparum pathway. These data suggest that our approach can be used to discover novel facets of host/malaria parasite biology in a high-throughput manner. 相似文献
48.
Nedelska Z Andel R Laczó J Vlcek K Horinek D Lisy J Sheardova K Bures J Hort J 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(7):2590-2594
Cognitive deficits in older adults attributable to Alzheimer's disease (AD) pathology are featured early on by hippocampal impairment. Among these individuals, deterioration in spatial navigation, manifested by poor hippocampus-dependent allocentric navigation, may occur well before the clinical onset of dementia. Our aim was to determine whether allocentric spatial navigation impairment would be proportional to right hippocampal volume loss irrespective of general brain atrophy. We also contrasted the respective spatial navigation scores of the real-space human Morris water maze with its corresponding 2D computer version. We included 42 cognitively impaired patients with either amnestic mild cognitive impairment (n = 23) or mild and moderate AD (n = 19), and 14 cognitively intact older controls. All participants underwent 1.5T MRI brain scanning with subsequent automatic measurement of the total brain and hippocampal (right and left) volumes. Allocentric spatial navigation was tested in the real-space version of the human Morris water maze and in its corresponding computer version. Participants used two navigational cues to locate an invisible goal independent of the start position. We found that smaller right hippocampal volume was associated with poorer navigation performance in both the real-space (β = -0.62, P < 0.001) and virtual (β = -0.43, P = 0.026) versions, controlling for demographic variables, total brain and left hippocampal volumes. In subsequent analyses, the results were significant in cognitively impaired (P ≤ 0.05) but not in cognitively healthy (P > 0.59) subjects. The respective real-space and virtual scores strongly correlated with each other. Our findings indicate that the right hippocampus plays a critical role in allocentric navigation, particularly when cognitive impairment is present. 相似文献
49.
50.
Mehmet Odabasi Cengiz Eris Mehmet Kamil Yildiz Hasan Abuoglu Sami Akbulut Abdullah Saglam 《International surgery》2013,98(3):277-281
Hepatic artery aneurysms are responsible for 12% to 20% of all visceral arterial aneurysms. Because most patients are asymptomatic, this disease is generally diagnosed incidentally during radiologic examination. Aneurysm rupture develops in 14% to 80% of cases, depending on the aneurysmatic segment''s diameter and location, as well as other etiologic factors. Mortality rates associated with rupture range between 20% and 70%. Thus, early diagnosis and timely initiation of medical interventions are critical to improve survival rates. Here, we present a male patient, age 69 years, with a hepatic artery aneurysm that was detected incidentally. The 3-cm aneurysm was detected on contrast-enhanced computed tomography and extended from the common hepatic artery to the hepatic trifurcation. A laparotomy was performed using a right subcostal incision. After dissection of the hepatoduodenal ligament, the common, right, and left hepatic arteries, as well as the gastroduodenal artery, were suspended separately. Then, the aneurysmatic hepatic artery segment was resected, and the gastroduodenal artery stump was ligated. An end-to-end anastomosis was formed between the left and common hepatic arteries, followed by an end-to-end anastomosis formed between the right hepatic artery and splenic artery using a splenic artery transposition graft. Postoperative follow-up examinations showed that both hepatic arterial circulations were good, and no splenic infraction had developed. 相似文献