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21.
Summary 1. Action-concentration curves have been plotted for the stimulation of the cat's superior cervical ganglion by acetylcholine. The free and the innervated receptors of the postsynaptic membrane, described by the authors, have been studied separately from this point of view.2. In the case of both the free and the innervated receptors, the action-concentration curves were similar in shape to the enzyme-substrate curve of cholinesterase. Analyzing these curves by the method of Lineweaver and Burk, in the case of free receptors, the dissociation constants of acetylcholine turned out to be: with stimulating RS complexes: 5.4·10–6–2.1·10–5M, with inhibitory RS
2 complexes: 3.2·10–5 – 5.2·10–5 M. The pertaining values for innervated receptors were 3.45 · 10–5 and 2.22 · 10–4 M, respectively.3. The parallelisms and divergences between the cholinesterase and acetylcholine-receptor functions are discussed.With 4 Figures in the Text 相似文献
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A dihydropyridine pyridinium salt redox carrier-based chemical delivery system for benzylpenicillin (1) was complexed with 2-hydroxypropyl--cyclodextrin (HPCD). The solubility of the lipophilic 1, which is incompatible with aqueous formulations, was dramatically increased and showed a linear dependency on the HPCD concentration. The degree of incorporation was 20 mg of 1 per g of complex. The stability study of 1 in various pH buffers indicated the base-catalyzed hydrolysis of the acyloxyalkyl linkage and the hydration of the 5,6 double bond of the dihydropyridine as the main degradation processes. The overall loss of 1, which follows first-order kinetics, was not influenced by changes in ionic strength and elimination of oxygen from the reaction medium. The HPCD complex of 1, which has a stability constant of 720–940 M
–1, stabilized the chemical delivery system. The influence of the temperature on the stability of 1 is also discussed. 相似文献
27.
Joseph P. Eder Anthony D. Elias Lois Ayash Catherine A. Wheeler Thomas C. Shea Lowell E. Schnipper Emil Frei III Karen H. Antman 《Cancer chemotherapy and pharmacology》1991,29(1):61-65
Summary Cyclophosphamide demonstrates enhanced tumoricidal activity with decreased bone marrow toxicity when given on a divided-dose schedule in certain animal models. A total of 22 patients presenting with refractory metastatic cancer were treated in a phase I trial of continuous infusion of cyclophosphamide over 96 h. Granulocytopenia of <500/l that lasted for > 14 days or thrombocytopenia of <25,000/l that lasted for > 14 days was the target dose-limiting toxicity in the absence of nonhematologic grade 4 toxicity. The maximal tolerated dose was 7 g/m2. Three patients died. Of 21 evaluable patients, 9 responded, including 8/9 who had experienced disease progression during prior oxazaphosphorine-containing combination chemotherapy. Clinically meaningful responses were observed in patients who had demonstrated clinical resistance to an oxazaphosphorine drug given at lower doses.Supported in part by U.S. Public Health Service grant P01CA-38493 and by a grant from the Mather's Foundation. Two of the authors (J. P. E. and A. D. E.) are recipients of Career Development awards from the American Cancer Society, and one (T. C. S.) is a recipient of a Faculty Development Award from the Pharmaceutical Manufacturer's Association Foundation 相似文献
28.
In urology, replacement of organs or organ segments has proved problematic. Current techniques do not replicate complete
organ function, and they cause well-known complications. With the acellular organ-specific matrix we have found a way to regenerate
tissue components seen in the normal lower urinary tract. The time required for regeneration depends on the matrix size and
function. The matrix is covered by urothelium migrating from the host, after which neovascularization occurs, followed by
formation of smooth-muscle cells and nerves. In our studies, normal muscle lining and nerves providing functional tissue were
demonstrable and no sign of antigenicity was evident, even after heterologous grafting. The regenerated rat bladder was evaluated
by organ bath as well as by in vivo functional tests and demonstrated properties and functions similar to those of host tissue.
Besides our obtaining encouraging results in the rat bladder, we also studied the organ-specific acellular matrix in other
species (dog and rabbit) and other organ segments (ureter and urethra). 相似文献
29.
Thomas C Dowling Mahiyar Arjomand Emil T Lin Loyd V Allen Mary Lynn McPherson 《American journal of health-system pharmacy》2004,61(23):2541-2544
PURPOSE: The bioavailability of a single, topically applied, 200-mg dose of ketoprofen (delivered in a ketoprofen 20% gel) relative to a single 50-mg oral dose in healthy volunteers was studied. METHODS: This was an open-label crossover study. The subjects were randomized to receive an oral 50-mg ketoprofen capsule or a single topical dose of ketoprofen 20% in a poloxamer-lecithin organogel (PLO). Treatment was followed by a one-week washout period. Blood samples were collected at intervals up to 10 hours after administration, and plasma ketoprofen concentrations were determined by high-performance liquid chromatography with ultraviolet or mass spectrometry detection. Noncompartmental pharmacokinetic values were obtained after each dose, and relative bioavailability was calculated. RESULTS: Eight healthy volunteers enrolled in and completed the study. Topical absorption of ketoprofen was highly variable among the subjects over the 10-hour sampling period. The median oral maximum plasma concentration (Cmax) exceeded the topical Cmax by nearly 200-fold (4.15 versus 0.021 microg/mL) (p = 0.001). The median relative bioavailability of topical ketoprofen was 0.48%, with individual subjects' values ranging from 0.18% to 2.1%. CONCLUSION: The relative bioavailability of ketoprofen was low and highly variable when the drug was administered as a single dose in a PLO-based ketoprofen 20% gel. 相似文献
30.
Trichodermamides A and B,cytotoxic modified dipeptides from the marine-derived fungus Trichoderma virens 总被引:4,自引:0,他引:4
Garo E Starks CM Jensen PR Fenical W Lobkovsky E Clardy J 《Journal of natural products》2003,66(3):423-426
Trichodermamides A (1) and B (2), two modified dipeptides, have been isolated from cultures of the marine-derived fungus Trichoderma virens. The trichodermamides possess a rare cyclic O-alkyl-oxime functionality incorporated into a six-membered ring. The structure of trichodermamide B was established by X-ray diffraction analysis, while the structure assignment of trichodermamide A, and determination of the absolute stereochemistry, was accomplished by spectral and chemical methods. Trichodermamide B displayed significant in vitro cytotoxicity against HCT-116 human colon carcinoma with an IC(50) of 0.32 microg/mL. 相似文献