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101.
102.
Li Shihong Schöneich Christian Wilson George S. Borchardt Ronald T. 《Pharmaceutical research》1993,10(11):1572-1579
The effect of primary structure and external conditions on the oxidation of methionine to methionine sulfoxide by the ascorbate/Fe3+ system was studied in small model peptides. Degradation kinetics and yield of sulfoxide formation were dependent on the concentration of ascorbate and H+, with a maximum rate observed at pH 6–7. Phosphate buffer significantly accelerated the peptide degradation compared to Tris, HEPES, and MOPS buffers; however, the formation of sulfoxide was low. The oxidation could not be inhibited by the addition of EDTA. Other side products besides sulfoxide were observed, indicating the existence of various other pathways. The influence of methionine location at the C terminus, at the N terminus, and in the middle of the sequence was investigated. The presence of histidine in the sequence markedly increased the degradation rate as well as the sulfoxide production. The histidine catalysis of methionine oxidation occurred intramolecularly with a maximum enhancement of the oxidation rate and sulfoxide production when one residue was placed between the histidine and the methionine residue. 相似文献
103.
Richard B. Dewey Jr Surendra D. Rao Stephanie L. Holmburg Ronald G. Victor 《European journal of neurology》1998,5(6):593-599
Eight patients with parkinsonism who developed severe orthostatic sypotension, were treated with oral ergotamine/caffeine. Significant long-term improvement in standing systolic blood pressure and symptoms of syncope and light-headedness were observed in four of these patients. One patient in whom the drug was effective discontinued it because of nausea. Another lost benefit after 2 weeks of sucessful therapy. Significant supine systolic hypertension occureed in only one patient, which was easily managed by nifedipine given at night. Symptoms or signs of ergotism were not observed. Oral ergotamine/caffeine should be considered as a cost-effective teratment for refactory orthostatic hypotension in carefully selected patients with parkinsonism. 相似文献
104.
Buprenorphine, a partial mu-opioid receptor agonist, has been proposed as a treatment for cocaine abuse. However, studies
in animals have produced conflicting results on the nature of the interaction between buprenorphine and cocaine. In some studies,
buprenorphine attenuated the effects of cocaine and in others it enhanced them. The purpose of the present study was to evaluate
the interaction of buprenorphine and cocaine on the rotational behavior of the nigrally-lesioned rat. Both buprenorphine (0.003–0.1
mg/kg) and cocaine (1.0– 30 mg/kg) alone produced dose-dependent increases in rotational behavior. Buprenorphine produced
long-lasting turning with a peak at 60 min after administration, while cocaine produced turning that peaked immediately after
administration and lasted for about 2 h. To distinguish simple additivity from other possible outcomes, we determined the
relative potency of each drug alone, using a defined level of effect: 150 turns above the saline control in 4 h. This effect
was produced by 10.0 mg/kg cocaine alone and by 0.0175 mg/kg buprenorphine alone. Based on these results, fixed ratio combinations
were tested and the experimentally derived effects were compared to the theoretically additive values, using an isobolographic
analysis. The fixed ratio combinations of the two drugs tested produced turning greater than predicted from simple additivity.
This finding provides statistically-supported evidence for synergism between the actions of buprenorphine and cocaine.
Received: 28 January 1997 / Final version: 7 June 1997 相似文献
105.
Wong Joseph Kuu Wei-Youh Burke Ronald Johnson Robert Wood Ray W. 《Pharmaceutical research》1995,12(1):144-148
The primary objective of this work was to establish a method to simulate the plasma levels of cilastatin, a model drug, following an intravenous in-line delivery scheme. In-vivo data in dogs obtained from this work were used to demonstrate the validity of the proposed approach. The in-line drug delivery system consists of a drug containing device which is placed between a large volume parenteral and a patient. Numerous advantages have been identified for this automatic in-line reconstitution delivery system. The numerical convolution integral algorithm was used in this work to perform plasma profile simulation. The results indicated that the simulated cilastatin plasma profile following in-line delivery closely agreed with the in-vivo data. 相似文献
106.
107.
Diarrhea has been reported as an early, mild, and uncommon complication of carbamazepine (CBZ) therapy. We report three cases of intractable diarrhea induced by CBZ necessitating discontinuation of the drug. 相似文献
108.
Gregory P Crucian Anna M Barrett David W Burks Alonso R Riestra Heidi L Roth Ronald L Schwartz William J Triggs Dawn Bowers William Friedman Melvin Greer Kenneth M Heilman 《Journal of the International Neuropsychological Society》2003,9(7):1078-1087
Deficits in visual-spatial ability can be associated with Parkinson's disease (PD), and there are several possible reasons for these deficits. Dysfunction in frontal-striatal and/or frontal-parietal systems, associated with dopamine deficiency, might disrupt cognitive processes either supporting (e.g., working memory) or subserving visual-spatial computations. The goal of this study was to assess visual-spatial orientation ability in individuals with PD using the Mental Rotations Test (MRT), along with other measures of cognitive function. Non-demented men with PD were significantly less accurate on this test than matched control men. In contrast, women with PD performed similarly to matched control women, but both groups of women did not perform much better than chance. Further, mental rotation accuracy in men correlated with their executive skills involving mental processing and psychomotor speed. In women with PD, however, mental rotation accuracy correlated negatively with verbal memory, indicating that higher mental rotation performance was associated with lower ability in verbal memory. These results indicate that PD is associated with visual-spatial orientation deficits in men. Women with PD and control women both performed poorly on the MRT, possibly reflecting a floor effect. Although men and women with PD appear to engage different cognitive processes in this task, the reason for the sex difference remains to be elucidated. 相似文献
109.
Ajit K. Shah Richard C. Brundage Kathleen D. Lake Ronald J. Sawchuk 《Biopharmaceutics & drug disposition》1995,16(1):59-70
We estimated the free fraction (fu) of cyclosporine (CyA) in the plasma from concentrations of CyA in urine (Cu) and plasma (Cp), urine flow rate (UF), and glomerular filtration rate in rabbits and in heart transplant patients. Following intravenous administration of CyA (5–30 mg kg?1) in ten NZW rabbits and oral administration of CyA (4.8–12.1 mg kg?1) in nine heart transplant patients, CyA concentrations in urine and plasma were measured by HPLC. The ratios of Cu to Cp and UF data were fitted to a physiological model of renal clearance using NONMEM. The free fraction of cyclosporine in the rabbits and the heart transplant patients was 0.0122 and 0.14, respectively. Because of the relatively low permeability of CyA across the tubular epithelium, no apparent equilibrium between Cu and Cp at any urine flow rate was reached and, therefore, the Cu to Cp ratio will not be equal to fu. 相似文献
110.
Kazunori Ikebe Kentaro Morii Jumpei Kashiwagi Takashi Nokubi Ronald L Ettinger 《Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics》2005,99(6):704-710
OBJECTIVE: The purpose of this study was to determine the association of dry mouth with oral symptoms and function, such as denture instability, discomfort, soreness in denture-bearing tissue, and dissatisfaction with chewing, tasting, or speaking in removable denture wearers. STUDY DESIGN: The subjects were 493 removable denture wearers with a mean age of 67.3 years. Perception of oral dryness was measured by a questionnaire. A multiple logistic regression analysis was used to determine the effect of the dry mouth on oral symptoms and function after controlling for age and gender. RESULTS: Oral dryness during eating was related to dissatisfaction with chewing (odds ratio, 10.5; P < .001) and speaking (odds ratio, 3.5; P < .05) and overall dissatisfaction (odds ratio, 6.3; P < .01) in complete denture wearers. Feeling of dry mouth was likely to be associated with soreness in denture-bearing tissues in both complete and removable partial denture wearers. CONCLUSIONS: There was a significant association of the perception of dry mouth among a group of denture wearers with oral symptoms and function. 相似文献