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排序方式: 共有102条查询结果,搜索用时 31 毫秒
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Khojasteh SC Leipold DD Lai F La H Baumgardner MJ Desino KE Gudmundsson OS Bloedow DC Bodary SC Reynolds ME Gadek TR Kenkare-Mitra S 《Xenobiotica; the fate of foreign compounds in biological systems》2008,38(3):340-352
Intercellular adhesion molecule (ICAM)-1988 is a small molecule lymphocyte function-associated antigen-1 (LFA-1) antagonist being considered for its anti-inflammatory properties. Following intravenous administration of ICAM1988, clearances in mice, rats, dogs, and monkeys were 17.8, 3.31, 15.4, and 6.85 ml min(-1) kg(-1), respectively. In mass balance studies using [(14)C]-ICAM1988 in rats dosed intravenously, unchanged ICAM1988 contributed to 25.1% of the dose. In rats, the systemic bioavailability of ICAM1988 was improved to 0.28 when the drug was administered orally as its isobutyl ester, ICAM2660. In rats, this was consistent with the complete in vitro conversion of ICAM2660 to ICAM1988 in plasma, and liver and intestinal S9. In dogs and monkeys, ICAM2660 did not improve the bioavailability of ICAM1988. This is consistent with limited in vitro conversion of ICAM2660 to ICAM1988 in plasma and liver S9. In human in vitro studies, ICAM2660 conversion to ICAM1988 in liver was similar to rats while no conversion in plasma and intestinal S9 fractions were observed. Based on the in vitro metabolism similarities of human and rat, it would be anticipated that in human oral administration of ICAM2660 would improve the systemic exposure of ICAM1988. 相似文献
95.
Elham Khojasteh Christopher J. Bockisch Dominik Straumann Stefan C. A. Hegemann 《The European journal of neuroscience》2013,37(1):141-149
Spontaneous nystagmus (SN) is a symptom of acute vestibular tone asymmetry. Alexander's Law (AL) states that slow‐phase velocity of SN is higher when looking in the direction of fast‐phases of nystagmus and lower in the slow‐phase direction. Earlier explanations for AL predict that during SN, slow‐phase eye velocity is a linear function of eye position, increasing linearly as eye deviates towards the fast‐phase direction. Recent observations, however, show that this is often not the case; eye velocity does not vary linearly with eye position. Such new findings necessitate a re‐evaluation of our understanding of AL. As AL may be an adaptive response of the vestibular system to peripheral lesions, understanding its mechanism could shed light on early adaptation strategies of the brain. Here, we propose a physiologically plausible mechanism for AL that explains recent experimental data. We use a dynamic control system model to simulate this mechanism and make testable predictions. This mechanism is based on the known effects of unilateral vestibular deficit on the response of the ipsi‐ and contralesional vestibular nuclei (VN) of the brainstem. This hypothesis is based on the silencing of the majority of ipsilesional VN units, which creates an asymmetry between the responses of the ipsi‐ and contralesional VN. Unlike former explanations, the new hypothesis does not rely on lesion detection strategies or signals originating in higher brain structures. The proposed model demonstrates possible consequences of acute peripheral deficits for the function of the velocity‐to‐position neural integrator of the ocular motor system and the vestibulo‐ocular reflex. 相似文献
96.
Amir Ali Rahsepar Asadollah Mirzaee Fatemeh Moodi Mohsen Moohebati Shima Tavallaie Fatemeh Khorashadizadeh Behrooz Mottahedi Jamil Esfehanizadeh Ali Azari Roshanak Khojasteh Somayeh Mousavi Roghayeh Paydar Maral Amini Majid Ghayour-Mobarhan Gordon A. Ferns Amirhossein Sahebkar 《Medical principles and practice》2015,24(5):424-431
Objective
To compare the changes in anti-malondialdehyde-modified low-density lipoprotein (MDA-LDL) IgG levels among patients undergoing off-pump and on-pump coronary artery bypass grafting (CABG) or valvuloplasty.Subjects and Methods
A total of 38, 39 and 34 patients who underwent off-pump CABG, on-pump CABG and valvuloplasty, respectively, were enrolled in this study. Serum anti-MDA-LDL IgG values were measured 24 h before and after the operative procedures and at discharge. Echocardiography was also done before surgery and before discharge. The results were compared with values from 50 healthy controls.Results
In all patients, a reduction in antibody titers was observed post-operatively. However, the decrease was significant only in the off-pump CABG–before surgery: 42.33 (25.83–58.51), after surgery: 30.86 (16.36–51.33) and at discharge: 10.96 (6.82–23.57; p = 0.027). There was a significant positive association between anti-MDA-LDL IgG levels and ejection fraction (r = 0.248, p = 0.036) and a negative association with E/E'', a marker of pulmonary capillary wedge pressure, in the coronary patients (r = −0.345, p = 0.012), but no significant associations were found in patients with valvular heart disease.Conclusions
Serum anti-MDA-LDL IgG levels were associated with cardiac function indices in coronary patients undergoing CABG.Key Words: Anti-malondialdehyde-modified low-density lipoprotein, Valvular heart disease, Coronary artery bypass grafting, Cardiac function 相似文献97.
98.
Mukadam S Tay S Tran D Wang L Delarosa EM Khojasteh SC Halladay JS Kenny JR 《Drug Metabolism Letters》2012,6(1):43-53
Early in the drug discovery process, the identification of cytochrome P450 (CYP) time-dependent inhibition (TDI) is an important step for compound optimization. Here we describe a high-throughput, automated method for the evaluation of TDI utilizing human liver microsomes and conventional CYP-specific mass spectrometer-based probes in a 384-well format. One of the key differences from other published TDI assays is the use of a shift in area the under curve of the percent activity remaining versus inhibitor concentration plot (AUC shift) rather than the traditional fold-shift in IC50, to determine the magnitude of TDI. An AUC shift of < 15% suggests negative TDI and > 15% suggests potential TDI. This AUC shift was used to achieve quantitative data reporting, even in the case of weak inhibitors for which IC50 values cannot be quantified. An Agilent Technologies BioCel 1200 System was programmed such that the TDI liability of up to 77 test compounds, incubated at four test concentrations, with and without NADPH in the pre-incubation, can be analyzed in a single run. The detailed automated methodology, assay validation, data reporting and the novel TDI AUC shift approach to describe magnitude of TDI are presented. 相似文献
99.
Gina Ziegler Dorette Freyer Denise Harhausen Uldus Khojasteh Wilfried Nietfeld George Trendelenburg 《Journal of cerebral blood flow and metabolism》2011,31(2):757-766
Reduced infarct volume in TLR2-knockout mice compared with C57Bl/6 wild-type mice has recently been shown in experimental stroke and confirmed in this study. We now also show a significant decrease of CD11b-positive cell counts and decreased neuronal death in the ischemic hemispheres of TLR2-deficient mice compared with C57Bl/6wt mice 2 days after transient focal cerebral ischemia. To examine the potential benefit of intravascular TLR2 inhibition, C57Bl/6wt mice were treated intraarterially with TLR2-blocking anti-TLR2 antibody (clone T2.5) after 45 minutes of cerebral ischemia and compared with control antibody (isotype) treated wild-type mice. Whereas T2.5-treated mice had no reduction in infarct volumes at 48 hours after reperfusion, they did have decreased numbers of CD11b-positive inflammatory cells and decreased neuronal death compared with isotype-treated control mice. Comparison of the isotype antibody treatment to control (saline) treatment showed no effects on infarct volumes or neuronal survival. However, mice treated with the control isotype antibody had increased numbers of CD11b-positive inflammatory cells compared with saline-treated animals. Thus, antibody treatment itself (i.e., control isotype antibody, but potentially of any antibody) may have adverse effects and limit therapeutic benefit of anti-TLR2-antibody therapy. We conclude that TLR2 mediates leukocyte and microglial infiltration and neuronal death, which can be attenuated by TLR2 inhibition. The TLR2 inhibition in vivo improves neuronal survival and may represent a future stroke therapy. 相似文献
100.
Mahboubeh Hajiabdolbaghi Nooshin Razani Nazli Karami Parastoo Kheirandish Minoo Mohraz Mehrnaz Rasoolinejad Khojasteh Arefnia Zahra Kourorian George Rutherford Willi McFarland 《AIDS education and prevention》2007,19(6):519-530
Despite high rates of HIV among male injection drug users, the sexual behaviors of at-risk women in Iran remain unknown. A questionnaire on HIV knowledge and risk behavior was administered in a Tehran nongovernmental organization targeting runaways and other women seeking safe haven. Half (total N = 50) were less than 24 years old; baseline HIV knowledge was high. The few who acknowledged using illicit substances said they used "frequently." Nonresponse rates to questions regarding sexual behavior were high (12 of 50). Half admitted a history of sexual activity; 40% of those reported their first sexual contact with someone other than their husband; three people had multiple partners. Three women reported a history of rape. Zero (97.5% one-sided confidence interval [CI] = 0, 0.17) of 35 women tested positive for HIV or syphilis. This study documents the existence of sexual behavior in a population of Iranian women, represents one of the first attempts at sexual research in the Iranian context, and highlights challenges in surveying this vulnerable group. 相似文献