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101.
102.
Septic or inflammatory stimuli suppress drug metabolism by cytochrome P-450 in the liver, presumably at the pretranslational level. We have shown previously that nitric oxide is responsible at least in part for the inhibition by bacterial lipopolysaccharide of phenobarbital-induced CYP2B1/2 activity in vivo. This was attributed to the interaction of nitric oxide with heme in the active-center of cytochrome P450, leading to enzyme inactivation. Here, we report of nitric oxide with heme in the active-center of cytochrome P450, leading to enzyme inactivation. Here, we report that endogeneous nitric oxide also contributes to LPS-induced suppression of CYP2B1/2 in vivo by down-regulating the expression of CYP2B1/2 protein and mRNA. 相似文献
103.
CM Reid M. Nelson P. Beckinsale P. Ryan LMH Wing LJ Beilin MA Brown GLR Jennings CI Johnston J. Marley JJ McNeil TO Morgan J. Shaw ID Steven MJ West 《Clinical and experimental pharmacology & physiology》1997,24(5):370-373
1. The present study aimed to determine the feasibility of conducting a 5 year cardiovascular outcome trial of the treatment of 6000 elderly hypertensive patients in Australian general practices. 2. General practitioners (GPs) were invited to participate by mail and personal follow-up. Patient records were reviewed to identify subjects for a blood pressure (BP) screening programme. Blood pressure was measured on three occasions and eligible subjects were included if the average BP was 160 mmHg systolic or 90 mmHg diastolic if systolic BP was 140 mmHg. 3. Seven hundred and forty-one GPs were approached and 89 were enrolled in the study (12% of mail invites and 75% of those receiving a personal contact). In 16 practices where screening was completed, 82 000 records were reviewed to identify 4% patients eligible for screening. Twenty-two per cent of eligible subjects attended screening. Of 1938 subjects screened, 180 (9%) had BP 5=160/90 mmHg. Forty-seven percent of subjects (n = 916) were receiving antihypertensive therapy and 184 (20%) were withdrawn from therapy. One hundred and sixteen (63%) of these subjects had BP return to study entry levels within 6 weeks. Fifty-seven newly diagnosed and 81 previously treated subjects were randomized (7% of the screened population). 4. Based on the high participation rate of GPs, the response rate of patients to attend a BP screening programme and the 7% randomization to screening ratio for entry into the study, the ANBP2 pilot study has demonstrated that it is feasible to recruit subjects from Australian general practices to a cardiovascular outcome trial. 相似文献
104.
The organization of motor responses in the orbicularis oris muscle following the delivery of punctate mechanical inputs to vermilion skin of the lips was studied in a group of young infants, school-age children, and adults during periods of voluntary lip muscle activation. A specially designed multi-point array skin contactor, coupled to a position-servo controlled linear motor, was highly effective in driving the early component of the perioral reflex (R1). Overall, the evoked R1 response obtained from the infant was of variable amplitude relative to the children and adults, lacked response specificity, and occurred it a longer latency. This brainstem mediated sensorimotor action appears to take on several characteristics of the adult form by the age of 12. The emergence and maturation of mechanically evoked perioral reflexes is discussed in relation to the acquisition of motor skills, including speech and smiling. 相似文献
105.
Dr. Thomas C. Hardin Pharm.D. FCCP Dr. Steven C. Butler M.D. Dr. Sabine Ross M.D. Dr. John H. Wakeford Pharm.D. Dr. James H. Jorgensen Ph.D. 《Pharmacotherapy》1994,14(2):147-152
Study Objectives . To evaluate the pharmacodynamic antibacterial activity of ticarcillin-clavulanic acid (T-C) and ampicillin-sulbactam (A-S) combinations against reference bacterial strains in patients with end-stage renal disease maintained on long-term hemodialysis. Design . Randomized, crossover, controlled study. Setting . National Institutes of Health-funded general clinical research unit in a Veterans Administration Medical Center. Patients . Nine adult men with end-stage renal disease maintained on long-term hemodialysis. Two subjects did not complete the study due to problems of vascular access, and another withdrew for personal reasons. Interventions . On a nondialysis day, each subject was randomly administered either T-C 3.1 g or A-S 3 g as a slow intravenous infusion over 30 minutes. Serial blood samples were collected for measurement of antibiotic serum concentrations and determination of serum bactericidal titers. Following a washout period, the study was repeated with the alternative antibiotic combination. Measurements and Main Results . The mean observed apparent β-half-life of clavulanic acid was substantially shorter than that for the other three drugs. The bactericidal activity of both A-S and T-C against non-β-lactamase-producing (Nβ-LP) strains of S. aureus and E. coli was consistently high, as indicated by geometric mean SBTs of at least 1:5 at 24 hours. Against β-lactamase-producing (β-LP) S. aureus, the geometric mean SBTs for A-S were at least 1:25 throughout the study period, while the geometric mean SBTs for T-C decreased over 24 hours from 1:29 to 1:6. Against β-LP E. coli, the bactericidal activities for both A-S and T-C were poor, with geometric mean peak SBTs of only 1:6 and 1:3, respectively. The geometric mean SBT for T-C against this E. coli strain had declined to 1:1 at 6 hrs. Conclusion . Increasing the dosing interval for T-C in patients with end-stage renal disease may lead to periods of insufficient clavulanic acid to protect ticarcillin from β-lactamase degradation. 相似文献
106.
There is growing interest in the phenomenon of long-term depression (LTD) of synaptic efficacy that, together with long-term potentiation (LTP), is a putative information storage mechanism in mammalian brain. In neural network models, multiple learning rules have been used for LTD induction. Similarly, in neurophysiological studies of hippocampal synaptic plasticity, a variety of activity patterns have been effective at inducing LTD, although experimental paradigms are still being optimized. In this review the authors summarize the major experimental paradigms and compare what is known about the mechanisms of LTD induction. Although all paradigms appear to initiate a cascade of events leading to an elevated level of Ca2+ postsynaptically, the extent to which these paradigms involve common expression mechanisms has not yet been tested. The authors discuss several critical experiments that would address this latter issue. Numerous questions about the properties and mechanisms of LTD(s) in the hippocampus remain to be answered, but it is clear that LTD has finally arrived, and will soon be attracting attention equal to its flip side, LTP. © 1994 Wiley-Liss, Inc. 相似文献
107.
108.
High-Temperature Short-Time Heat Inactivation of HIV and Other Viruses in Human Blood Plasma 总被引:4,自引:0,他引:4
Stanley E. Charm Steven Landau Bolanle Williams Bernard Horowitz Alfred M. Prince and Donna Pascual 《Vox sanguinis》1992,62(1):12-20
An ultra-short-time heating system was used to process blood plasma spiked with various viruses (HIV, vesicular stomatitis virus, encephalomyocarditis virus). Virus reduction and recovery of plasma proteins were measured at various temperatures from 65 to 85 degrees C. Processing at 77 degrees C and 0.006 s resulted in a high level of virus kill, including greater than or equal to 4.4 log10 HIV, while maintaining protein structure and activity essentially intact. 相似文献
109.
110.
Dr Arthur J. L. Schneider MD W. Bosseau Murray MBChB MD Steven C. Mentzer BS Fernando Miranda BS Sorin Vaduva MS 《Journal of clinical monitoring and computing》1995,11(6):358-364
Objective. The medical practitioner is faced with an increasing list of protocols and algorithms related to patient care. These recommendations are often difficult to recall, particularly in stressful emergency situations. Using advanced cardiac life support (ACLS) protocols, we built a computer-based system to exhibit precompiled response plans for medical emergencies. To validate the usefulness of this prompting device, we tested application of two of the nine ACLS algorithms, pulseless ventricular fibrillation/ventricular tachycardia (Vfib/Vtach) and bradycardia, in a simulated operating room (OR) environment.Methods. The system utilized the software authoring system IconAuthor (Aimtec Inc., Nashua, NH) and a touch-screen monitor (DiamondScan, Microtouch, Methuen, MA). Prior to testing our system, all 39 subjects were given time to familiarize themselves with its operation. Subsequently, all subjects were videotaped while managing a standard simulated anesthetic. During the anesthetic, the subjects were presented with two emergency scenarios, not viewed during the familiarization period. The electrocardiographic (EKG) signals for normal sinus rhythm, ventricular fibrillation, and second-degree heart block were presented. By random selection, the prompter was available to half of the subjects for help with arrhythmia management (experimental group), while to half it was not (control group).Results. A total of 39 subjects completed the exercise. Use of the prompter enabled significantly more subjects to administer correct drugs and dosages during ventricular fibrillation. The correct lidocaine dose was chosen more often by the experimental group than by the control (p=0.015); similarly MgSO4 was appropriately ordered more often in the experimental group (p=0.003). During second-degree heart block, atropine was correctly followed with a dopamine infusion (p=0.004), and epinephrine infusion was ordered for refractory bradycardia (p=0.002) more often in the experimental than the control group.Conclusions. These data demonstrate the value of a prompting device at the anesthesia workstation. We foresee the use of such prompters in many areas of medicine.This study was made possible by a grant from the Anesthesia Patient Safety Foundation. Results were presented, in part, at the meeting of the STA/SEA Orlando, Florida, January 1994. 相似文献