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71.
紫堇灵、乙酰紫堇灵及原鸦片碱对小鼠实验性肝损伤的保护作用 总被引:4,自引:0,他引:4
研究了紫堇灵、乙酰紫堇灵及原鸦片碱对小鼠实验性肝损伤的保护作用及其作用机理。小鼠预先分别ig紫堇灵、乙酰紫堇灵或原鸦片碱50及100mg·kg-12次,对CCl4、硫代乙酰胺、扑热息痛所致的小鼠肝损伤均有保护作用,使SGPT显著降低,肝病理损伤程度减轻。此3种成分在体外均能抑制CCl4引起的肝微粒体脂质过氧化及CCl4转化为CO。在上述实验中乙酰紫堇灵的作用均强于另外两种成分。另外,此3种成分对肝药酶有先抑制后诱导作用。 相似文献
72.
GT. Hischebeth TM. Randau MM. Ploeger MJ. Friedrich E. Kaup C. Jacobs E. Molitor A. Hoerauf S. Gravius MD. Wimmer 《Diagnostic microbiology and infectious disease》2019,93(2):125-130
Periprosthetic joint infections (PJIs) are a major complication in total joint arthroplasty. Staphylococcus aureus and coagulase-negative staphylococci are known to cause the majority of all PJIs. This study aimed to analyze the eradication rates of S. aureus and S. epidermidis with methicillin susceptibility and methicillin resistance in a 2-stage therapy algorithm. Seventy-four patients with PJI caused by methicillin-resistant S. aureus (MRSA), methicillin-resistant coagulase-negative staphylococci (MRSE), methicillin-susceptible S. aureus (MSSA), and methicillin-susceptible coagulase-negative staphylococci (MSSE) were included, and the outcome was analyzed retrospectively. After a minimal follow-up of 2?years, n?=?56 patients (75.7%) were definitively free of infection. The analysis revealed significant differences between the groups, with eradication rates as follows: MSSA (92.6%), MSSE (95.2%), MRSA (80%), and MRSE (54.2%). MRSE showed a significantly lower rate of patients graded as “definitively free of infection” as compared to patients with infections caused by MSSA, MSSE, and MRSA. 相似文献
73.
S Ve Ramesh MPhil Ronnie George MS Prema Raju BS Devi Sachi MS GT Sunil MS Lingam Vijaya MS 《Clinical & experimental optometry》2010,93(5):349-353
Background: The aim was to compare the severity of glaucoma among newly diagnosed patients presenting to a hospital‐based glaucoma care centre (HBGS: Sankara Nethralaya, Medical Research Foundation) with that of age matched subjects from the population‐based Chennai Glaucoma Follow‐up Study (CGFS). Methods: Newly diagnosed subjects with primary glaucoma from HBGS and age‐ and gender‐matched subjects from the urban arm of CGFS examined during the same time period were included. All subjects underwent comprehensive ocular examinations including Humphrey visual field (HVF: 24‐2 SITA Standard). Glaucoma was defined as: an intraocular pressure (IOP) of 22 or greater mmHg in either eye; vertical cup‐to‐disc ratio (VCDR) of 0.7 or greater or asymmetry 0.2 or more or the presence of focal thinning, notching or a splinter haemorrhage. All subjects had a minimum of three follow‐up visits and reliable visual fields. The IOP, vertical cup‐to‐disc ratio, mean deviation (MD) and pattern standard deviation (PSD) of the Humphrey field measurements at the third follow‐up visit of CGFS were compared for assessing the severity of glaucoma with the HBGS group. Results: Forty‐seven age‐matched subjects from both the study populations were selected. Significantly higher (p = 0.04) IOP was noted in the HBGS population than the CGFS, with a difference in mean IOP of 2.80 mmHg (95% CI of diff: 0.14 to 5.46). The mean ± SD of the mean deviation and pattern standard deviation were ‐6.92 ± 6.53 dB and 6.05 ± 4.20 dB among the HBGS and ‐4.47 ± 4.19 dB and 3.26 ± 2.69 dB among the CGFS population, respectively, the difference in the mean deviation (p = 0.036) and pattern standard deviation (p = 0.0001) were statistically significant. The mean vertical cup‐to‐disc ratio did not vary between populations (p = 0.14). Conclusion: Patients from the HBGS group had higher IOP and more severe visual field defects than the CGFS group. Hence, results from hospital‐based studies on severity and the rates of progression should be interpreted with caution. 相似文献
74.
MB Gill S Frausto M Ikoma M Sasaki M Oikawa R Sakai GT Swanson 《British journal of pharmacology》2010,160(6):1417-1429
Background and purpose:
A new class of heterotricyclic glutamate analogues recently was generated by incorporating structural elements of two excitotoxic marine compounds, kainic acid and neodysiherbaine A. Rather than acting as convulsants, several of these ‘IKM’ compounds markedly depressed CNS activity in mice. Here, we characterize the pharmacological profile of the series with a focus on the most potent of these molecules, IKM-159.Experimental approach:
The pharmacological activity and specificity of IKM compounds were characterized using whole-cell patch clamp recording from neurons and heterologous receptor expression systems, in combination with radioligand binding techniques.Key results:
The majority of the IKM compounds tested reduced excitatory synaptic transmission in neuronal cultures, and IKM-159 inhibited synaptic currents from CA1 pyramidal neurons in hippocampal slices. IKM-159 inhibited glutamate-evoked whole-cell currents from recombinant GluA2- and GluA4-containing α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) receptors most potently, whereas kainate and NMDA receptor currents were not reduced by IKM-159. Antagonism of steady-state currents was agonist concentration dependent, suggesting that its mechanism of action was competitive, although it paradoxically did not displace [3H]-AMPA from receptor binding sites. IKM-159 reduced spontaneous action potential firing in both cultured hippocampal neurons in control conditions and during hyperactive states in an in vitro model of status epilepticus.Conclusions and implications:
IKM-159 is an AMPA receptor-selective antagonist. IKM-159 and related nitrogen heterocycles represent structurally novel AMPA receptor antagonists with accessible synthetic pathways and potentially unique pharmacology, which could be of use in exploring the role of specific populations of receptors in neurophysiological and neuropathological processes. 相似文献75.
GT Whiteside JM Dwyer JE Harrison CE Beyer T Cummons L Manzino L Mark GH Johnston BW Strassle A Adedoyin P Lu MJ Piesla CM Pulicicchio JCL Erve BJ Platt ZA Hughes KE Rogers DC Deecher EJ Trybulski JD Kennedy P Zhang L Leventhal 《British journal of pharmacology》2010,160(5):1105-1118
Background and purpose:
Antidepressants, which raise the CNS concentrations of 5-HT and noradrenaline, are frequently used in the treatment of chronic pain; however, it is not known if increasing CNS noradrenaline levels alone is sufficient for efficacy, in part resulting from a lack of small molecules with sufficient selectivity.Experimental approach:
In this report, we present the in vitro pharmacological and in vivo pharmacokinetic and pharmacological properties of the novel, orally available and CNS penetrant inhibitor of the noradrenaline transporter (NET), WAY-318068 (1-[(1S,2R)-1-(3,5-difluorophenyl)-2-hydroxy-3-(methylamino)propyl]-7-fluoro-3,3-dimethyl-1,3-dihydro-2H-indol-2-one).Key results:
WAY-318068 is a potent and effective inhibitor of the NET with a Ki of 8.7 nM in a binding assay, and an IC50 of 6.8 nM in an assay of transporter function, without significant binding to the dopamine transporter. Furthermore, the compound has only weak activity at the 5-HT transporter, leading to a functional selectivity of greater than 2500-fold. It is orally bioavailable with substantial quantities of the compound found in the CNS after oral dosing. As measured by microdialysis in rats, the compound causes a robust and significant increase in cortical noradrenaline levels without affecting 5-HT. WAY-318068 was effective in models of acute, visceral, inflammatory, osteoarthritic, neuropathic, diabetic and bone cancer pain, as well as in traditional models of depression at doses that do not cause motor deficits.Conclusions and implications:
Collectively, the present results support the conclusion that selectively increasing CNS levels of noradrenaline is sufficient for efficacy in models of depression and pain. 相似文献76.
77.
78.
Digital and conventional chest imaging: a modified ROC study of observer performance using simulated nodules 总被引:5,自引:0,他引:5
A modified receiver operating characteristic (ROC) study was performed in which five readers were asked to locate multiple nodules on images of an anthropomorphic phantom obtained with a prototype digital radiographic chest unit and with a conventional chest unit. Results indicate that when nodules were projected over the lungs, a significantly greater number (significant at the 5% level) were identified on conventional radiographs, whereas for nodules projected over the mediastinum, the digital images were notably superior (difference significant at the 2% level). An error analysis of the multiple nodule problem and pseudo-ROC curves are presented. The modified ROC study does not suffer from the positional ambiguity inherent in most ROC studies and is efficient in acquiring data. 相似文献
79.
80.