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排序方式: 共有7032条查询结果,搜索用时 15 毫秒
31.
Robert H. Smallwood George W. Mihaly Richard A. Smallwood Denis J. Morgan 《Journal of pharmacokinetics and pharmacodynamics》1988,16(5):529-542
For substances eliminated from blood by the liver, the effect of a change in unbound fraction of drug (fu
b
)on steady state total (C
b
)and unbound (Cu
b
)blood concentrations has hitherto only been considered for the two limiting cases, i.e., at the upper and lower extremes of hepatic intrinsic clearance (CL
int
).For a substance of very low CL
int
,if fu
b
changes, C
t
will change and Cu
b
will remain constant, whereas if CL
int
isvery high, Cu
b
will change and C
b
will remain constant.The present study defines the effects of a change in fu
b
on C
b
and Cu
b
over the whole CL
int
range. Computer simulations were undertaken which predicted that, for a given change in fu
b
,absolute and relative changes in C
b
would decreasenonlinearly with increasing CL
int, twhile the relative change in Cu
b would increasewith CL
int
.The absolute change in Cub
would be independent of CL
int
.Significant changes in Cb and Cu
b would be observed at intermediate values of CL
int not just at the high and low extremes. These theoretical predictions were investigated experimentally in the isolated perfused rat liver by examining the effects of a change in fu
b of sodium taurocholate a substance with intermediate CL
int
(such that at fu
b
=0.27,hepatic extraction ratio=0.71) induced by concurrent administration of sodium oleate. Sodium 24-
14
C-taurocholate (specific activity 52 Ci/mmol) was infused into the reservoir in a recycling system at 30 mol/hr for 105 min (n=6). At 45 min a bolus dose of sodium oleate (50 mmol) was administered to the reservoir, followed by a constant infusion of 143 mmol/hr for 1 hr. Following the administration of oleate, taurocholate fu
b fell promptly by 55% (0.27–0.12). There was a relative increase of taurocholate C
b of 22.7% and a relative decrease in Cu
b of 45.4%, in accordance with the simulations (p<0.05). We conclude that important changes in unbound steady-state concentration, the pharmacologically active moiety, can occur upon changes in unbound fraction with compounds of intermediate hepatic intrinsic clearance.This study was supported by the National Health and Medical Research Council of Australia. 相似文献
32.
Albertini-Yagi CS Oliveira RC Vieira JE Negri EM de Oliveira LR Saldiva PH Lorenzi-Filho G 《Respiratory physiology & neurobiology》2005,145(1):101-110
The study objectives were to compare in vitro transportability and physical properties of respiratory mucus, obtained invasively by direct collection (DC) right after endotracheal intubation and non-invasively by sputum induction with 3% hypertonic saline solution inhalation (SI) 24 h before the anesthesia. Twenty-two patients with no pulmonary disease scheduled for elective abdominal surgical procedures were studied. The parameters analyzed and the main results are as follows. (1) Transportability by cilia (MCT), SI was higher than DC (0.94+/-0.25 and 0.62+/-0.25; P<0.001). There was a significant correlation between the two methods and DC could be estimated by: DC=0.21+(0.44 SI) (r=0.44; P<0.001). (2) Transportability by cough (CC), SI was higher than DC (68.23+/-32.1 and 33.58+/-19.04 mm; P=0.002). (3) Contact angle (CA), SI was lower than DC (10+/-3 degrees and 22+/-14 degrees ; P=0.025). (4) Rheological properties (no significant difference obtained between SI and DC). These results indicated that SI changes mucus physical properties and transportability in non-expectorators. 相似文献
33.
Tomoko Morikawa Ichiro Yamadori Takeshi Okino Tetsuro Ogino Masaki Ohmori 《Pathology international》1992,42(4):242-248
Two cell lines designated IC KMS and D KMS were established from human adenovirus type 12 induced tumors of C3Hf/OK mouse. The cell lines retained the characteristics of the original tumor i.e., production of numerous C type and intracisternal A-type particles, integration of Adl2 El region DNA and amplification of the myc gene family. Chromosomal analysis revealed chromosome aberrations in both IC KMS and D KMS cells. The modal chromosome number of IC KMS cells was 54 and that of D-KMS cells was 48. Metacentric chromosomes and mini-chromosomes were found. Trisomy of chromosome 3, 7 and 12 was seen frequently in D KMS cells. Although DNA aneuploidy was revealed by flow cytometry, the DNA indices of these cells showed no relation to the copy number of integrated Adl2 DNA. These cells have been propagated by serial culture during the past 17 months. Production of endogenous virus particles is a unique characteristic of IC KMS and D KMS cells. These cell lines would be useful materials for examining the contribution of Adl2 carcinogenesis to activation of endogenous virus particles, and also the correlation between Adl2 carcinogenesis and cancer related genes. Acta Pathol Jpn 42: 242-248, 1992. 相似文献
34.
Per Madsen Hanne L. Olesen Niels H. Secher M. Klokker 《European journal of applied physiology》1995,70(3):246-251
A double-blind paired protocol was used to evaluate, in eight male volunteers, the effects of the endogenous opiate antagonist naloxone (NAL; 0.05 mg· kg–1) on cardiovascular responses to 50° head-up tilt-induced central hypovolaemia. Progressive central hypovolaemia was characterized by a phase of normotensive-tachycardia followed by an episode of hypotensive-bradycardia. The NAL shortened the former from 20 (8–40) to 5 (3–10) min (median and range; (P < 0.02). Control head-up tilt increased the means of thoracic electrical impedance [from 35.8 (SEM 2.1) to 40.0 (SEM 1.8) ; P < 0.01 of heart rate [HR; from 67 (SEM 5) to 96 (SEM 8) beats · min–1, P < 0.02], of total peripheral resistance [TPR; from 25.5 (SEM 3.2) to 50.4 (SEM 10.5)mmHg min 1–1,P < 0.05] and of mean arterial pressure [MAP; from 96 (SEM 2) to 101 (SEM 2)mmHg, P < 0.02]. Decreases were observed in stroke volume [from 65 (SEM 12) to 38 (SEM 9) ml, P < 0.01], in cardiac output [from 3.7 (SEM 0.7) to 2.5 (SEM 0.5) 1 · mint, P < 0.01], in pulse pressure [from 55 (SEM 4) to 37 (SEM 3)mmHg, P < 0.01] and in central venous oxygen saturation [from 73 (SEM 2) to 59 (SEM 4)%, P < 0.01]. During NAL, mean HR increased from 70 (SEM 3); n.s. compared to control) to only 86 (SEM 9) beats · min–1 (P < 0.02 compared to control) and MAP remained stable. The episode of hypotensive-bradycardia appeared as mean control HR decreased to 77 (SEM 7)beats · min–1, TPR to 31.4(SEM 7.7)mmHg · min · 1–1 and MAP to 60 (SEM 5)mmHg (P < 0.01), and the volunteers were tilted supine. Cardiovascular effects of naloxone on central hypovolaemia included a reduced elevation of HR and blood pressures and provocation of the episode of hypotensive-bradycardia. 相似文献
35.
36.
Rorden C Driver J 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》2001,137(3-4):487-496
Research on visual attention has demonstrated that covert attention can be focused on particular locations within one hemifield,
but that a specific "meridian" cost may also be found for shifting attention between hemifields. These issues have received
less consideration for audition, even though reliable behavioral measures for the effects of spatial attention on hearing
are now available. We examined the spatial distribution of covert attention in an auditory task following spatially non-predictive
peripheral auditory cues (which should induce exogenous attention shifts), or following symbolic central cues that predicted
the likely location for the auditory target (to induce endogenous attention shifts). In both cases, we found that attention
can be focused not only on one hemifield versus another, but also within one hemifield in an auditory task. However, there
was no unequivocal evidence for a meridian effect in audition.
Electronic Publication 相似文献
37.
We calculated a Research Diagnostic Criteria (RDC) endogenous score for 257 depressed inpatients based on the number of endogenous criteria present. The distribution of RDC endogenous scores was unimodal. There was no association between endogenous scores and results of the Dexamethasone Suppression Test, or morbid risk for depression in the patients' first-degree relatives. The morbid risk for a family history of alcoholism tended to decrease with increasing endogenous scores, although a consistent steady decline was not observed. The results suggest that the RDC criteria do not fit either the categorical or dimensional model of endogenous classification. Potential sources of difficulty with the RDC endogenous criteria are discussed. 相似文献
38.
Blood coagulation and fibrinolysis after long-duration treadmill exercise controlled by individual anaerobic threshold 总被引:2,自引:0,他引:2
Hilberg T Gläser D Reckhart C Prasa D Stürzebecher J Gabriel HH 《European journal of applied physiology》2003,90(5-6):639-642
For rehabilitation training it is recommended that the intensity of exercise should be clearly below the individual anaerobic threshold (IAT). We investigated blood coagulation, particularly endogenous thrombin potential (ETP) and fibrinolysis following a standardized treadmill (TR) ergometer test at 90% IAT for 60–120 min. Sixteen healthy male non-smokers underwent the TR test. Blood samples were taken after a 30-min rest, immediately after exercise, and 2 h after exercise completion. Extrinsic and intrinsic total (TTPex+in) and endogenous (ETPex+in) thrombin potential, prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT), plasmin-2-antiplasmin complex (PAP), D-dimer, tissue plasminogen activator antigen and activity (tPA-AG and tPA-ACT) and plasminogen activator inhibitor type 1 antigen and activity (PAI-1-AG and PAI-1-ACT) were measured. Immediately after TR, F1+2, TAT and TTPex+in were increased (P<0.05) while ETPex+in remained unchanged. In contrast, PAP, D-dimer, tPA-AG, tPA-ACT (P<0.05) were distinctly enhanced while PAI-1-ACT was decreased (P<0.05) immediately after exercise. The changes in tPA-AG, tPA-ACT, and PAI-1-ACT were reversed to nearly baseline while the enhancement in PAP and D-dimer was prolonged by more than 2 h after exercise. Long-duration exercise between 60 and 120 min controlled by IAT (90%) on a TR ergometer only implicates a small increase in thrombin generation markers and total (free and 2-macroglubulin-bound thrombin), but not in endogenous (free) thrombin potential alone. In contrast, fibrinolysis is distinctly increased after this type of exercise. Endurance exercise with an intensity below 90% IAT and a duration below 2 h generates a more favourable condition for fibrinolysis than for blood coagulation in healthy young subjects. Data are given as mean (SD). 相似文献
39.
急性鸭乙型肝炎病毒感染病毒清除机理研究 总被引:2,自引:0,他引:2
目的 :进一步阐明嗜肝病毒自然感染过程中病毒清除机理。方法 :7只 2~ 3月龄成年重庆麻鸭静脉接种 10~ 2 0mlDHBV阳性血清 (5× 10 8~ 1× 10 9genome) ,接种后每周采血检测外周血中DHBVDNA、DHBsAg和特异抗体的产生 ;感染后第10、35天分离外周血单个核细胞用于抗原特异细胞增殖实验 ;第 5、30、6 0天取肝组织标本进行DHBVDNASouthern杂交、DHB sAg免疫组化及肝组织病理检测。结果 :DHBV感染成年鸭在 1~ 2w潜伏期后出现急性、一过性感染 ,感染高峰期肝内存在多拷贝的DHBV所有复制中间体形式 ,包括cccDNA。进一步分析显示病毒血症的消失是在快速抗原特异细胞增殖反应和高滴度特异抗体产生之后 ;与此同时 ,整个急性感染期间 ,肝细胞并无明显的损害。结论 :非细胞直接损伤机制在嗜肝病毒清除过程中发挥了重要作用。 相似文献
40.