Background: Ketamine is a potent bronchodilator that, in clinically used concentrations, relaxes airway smooth muscle in part by a direct effect. This study explored the role of calcium concentration (Ca2+) in this relaxation.
Methods: Canine trachea smooth muscle strips were loaded with the fluorescent probe fura-2 and mounted in a spectrophotometric system to measure force and intracellular calcium concentration ([Ca2+]i) simultaneously. Calcium influx was estimated using a manganese quenching technique. Cyclic nucleotides in the airway smooth muscle strips were measured by radioimmunoassay.
Results: In smooth muscle strips stimulated with submaximal (0.1 micro Meter) and maximal (10 micro Meter) concentrations of acetylcholine, ketamine caused a concentration-dependent decrease in force and [Ca2+]i. The sensitivity of the force response to ketamine significantly decreased as the intensity of muscarinic receptor stimulation increased; the median effective concentration for relaxation induced by ketamine was 59 micro Meter and 850 micro Meter for tissue contracted by 0.1 micro Meter or 10 micro Meter acetylcholine, respectively (P < 0.05). In contrast, the sensitivity of the [Ca2+] sub i response did not depend on the intensity of muscarinic receptor stimulation. Ketamine at 1 mM significantly inhibited calcium influx. Ketamine did not significantly increase cyclic nucleotide concentrations. 相似文献
Background: For local anesthetics, the process of removal from the site of administration influences the duration of anesthesia and the risk for systemic toxicity to develop. The systemic absorption of epidural ropivacaine and the time profile of sensory and motor block were studied in healthy volunteers.
Methods: Nine persons simultaneously received 150 mg ropivacaine hydrochloride (7.5 mg/ml) epidurally and 40 mg deuterium-labeled (sup 2 H sub 3)ropivacaine hydrochloride (0.25 mg/ml) intravenously. Peripheral arterial and venous plasma samples were collected, and assessments of sensory and motor block were made.
Results: The arterial plasma concentrations increased faster than the venous concentrations, with 50% higher maximum concentrations after both intravenous and epidural administration. The absorption was biphasic. A correlation was seen between the duration of sensory block and the slower absorption half-life; that is, the longer the half-life, the longer the duration. The extent of spread varied among the volunteers, with the median upper block level not exceeding T12. The motor block (Bromage score 1) was of slower onset (median, 0.4 h) and of shorter duration (median, 4.1 h) than the sensory block (onset, 0.2 h; duration, 6.5 h at L2 medians). 相似文献
Hepatic vascular changes are generally associated to fibrotic lesions of the liver but their role in the development and extension of fibrosis is not well known. By performing a portacaval anastomosis in rats, a proliferation of hepatic vessels was attained progressively, comparable to proliferations seen in cirrhosis and schistosomiasis. Such a modification of the hepatic vasculature was accompanied by changes in the connective matrix of the liver, mainly related to the vascular walls. Moreover, sinusoidal capillarization was detected at the electron microscopical level whereas no alterations could be seen neither in the distribution nor in the quality of the connective matrix proteins with Immunofluorescence technique. The only modification detected by light microscopy, at this zone, was the shrinked aspect of reticulin fibers which could be related to the important liver atrophy provoked by the anastomosis. It can be assumed that in liver pathology, selective changes occur in the connective matrix components depending on the type of injury. Necrotic and inflammatory processes lead mainly to the deposition of interstitial collagens and associated proteins, related to a diffuse stroma reaction resultant from activation of specific cell populations whereas in portacaval anastomosis, a selective increase of vascular connective matrix (mainly basement membrane components) occurs as a direct consequence of vessel proliferation. 相似文献
The need for an early identification of formulation and manufacturing factors that are important for setting satisfactory specification limits for the dissolution rate of an active substance from a dosage form is emphasized. A discriminatory dissolution test has to be developed based on experiences from early drug development, bioavailability/bioequivalence studies and clinical trials. References are given to guidelines of the EU-system and to the monographs and chapters of the European Pharmacopoeia, which have to be considered. The dissolution test is expected to be an appropriate tool for checking that the manufacture of dosage forms is consistent and successful and that each dosage unit of a batch will have pharmaceutical qualities that correspond to those on which the safety and efficacy documentation of a product is based. 相似文献
Previous research has shown that separation discrimination thresholds are independent of the internal spatial scale (local spatial frequency) of the targets whose separation is being judged. The experiments reported here tested the generality of this conclusion for separation discrimination of targets that were embedded in an array of identical objects, where crowding could enhance the importance of the scale at which the individual target locations are encoded. No effect of the local spatial scale of the targets was found under these conditions. 相似文献
OBJECTIVE: Heart failure (HF) and depression are both common in older adults, and the presence of depression is known to worsen HF outcomes. For community-dwelling older adults, admission to a nursing home (NH) is associated with loss of independent living and poor outcomes. The objective of this study was to examine the effect of depression on NH admission for older adults with HF. METHODS: Using the 2001-2003 National Hospital Discharge Survey datasets, the authors identified all community-dwelling older adults who were discharged alive with a primary discharge diagnosis of HF. The authors then identified those with a secondary diagnosis of depression. Using a multivariable logistic regression model, the authors then determined probability or propensity to have depression for each patient. The authors used propensity scores for depression to match all 680 depressed patients with 2,040 nondepressed patients. Finally, the authors estimated the association between depression and NH admission using bivariate and multivariable logistic regression analyses. RESULTS: Patients had a mean (+/- standard deviation) age of 79 (+/- 8) years, 72% were women, and 9% were blacks. Compared with 17% nondepressed patients, 25% depressed patients were discharged to a NH. Depression was associated with 50% increased risk of NH admission (unadjusted relative risk [RR]: 1.50; 95% confidence interval [CI]: 1.28-1.74). The association became somewhat stronger after multivariable adjustment for various demographic and care covariates (adjusted RR: 1.60; 95% CI: 1.35-1.68). CONCLUSION: In ambulatory older adults hospitalized with HF, a secondary diagnosis of depression was associated with a significant increased risk of NH admission. 相似文献
A new approach designed to establish the most suitable area for eccentric viewing and to teach and train patients with severe age-related macular degeneration (AMD) to use the eccentric viewing technique is described. Using a computer and video display based system, as well as software written specifically for this purpose, we investigated and trained ten consecutive patients with AMD. The patients were 80.1 ± 5.6 years old, on average. All of them had an absolute central scotoma. Mean visual acuity was 0.035 ± 0.016. After 30 min of testing, instruction and reading on the screen, followed by 2.6 ± 0.69 one-hour training sessions, on average, with the low vision therapist, reading newspaper and book texts with the aid of hyperoculars or aplanatic systems and a very short reading distance, the patients achieved a reading speed of 58.9 ± 19.7 words/min, significantly (p<0.001) higher than the initial speed when reading on the screen, 11.5 ± 4.5 words/min. 相似文献