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211.
Smith Philip Mirabelli Christopher Fondacaro Joseph Ryan Frederick Dent John 《Pharmaceutical research》1988,5(9):598-603
We have employed an in vitro system to study transport and metabolism of organic molecules by gastrointestinal tissues. Such a system would aid in the evaluation of the potential for oral delivery of organic molecules. Transport and metabolism of 5-fluorouracil (5-FU) were studied using rabbit intestinal preparations. Unidirectional fluxes and metabolism were measured in vitro in Ussing chambers under short-circuit conditions. Results from these studies reveal that in ileum, proximal, and distal colon, steady-state fluxes of 5-FU (10 µM added to both bathing solutions) are established after 30 min and remain constant for at least 110 min. Transport of 5-FU under sink conditions with 10 µM 5-FU present in the mucosal or serosal bathing solution alone demonstrated similar rates of transport as under nonsink conditions. The concentration dependence of 5-FU fluxes indicates that the mucosal (m)-to-serosal (s) flux is composed of both a saturable and a linear component over the range of 1–100 µM in the ileum, whereas the s-to-m flux in the ileum and both fluxes in the colon are linear functions of concentration. Over the concentration range employed and the time course of these studies, 5-FU had no effect on the electrical properties of the ileum or colon. In the ileum, the m-to-s but not the s-to-m flux of 5-FU was reduced by (1) serosal ouabain (0.1 mM); (2) reduction of the bathing solution Na concentration; and (3) addition of uracil, thy mine, thymidine, uridine, 2-deoxyuridine, or uridine-5-monophosphate. These results indicate that 5-FU absorption in the ileum occurs by a Na-dependent mechanism that is inhibited by uracil and structurally related compounds. In distal colon, no evidence for an active transport mechanism was obtained. High-performance liquid chromatography (HPLC) analysis reveals that both ileum and distal colon metabolize 5-FU to more polar compounds. Metabolism in ileum is quantitatively greater than in distal colon. Metabolites are found predominantly on the side to which transport has occurred, suggesting that metabolism occurs concomitantly with transport. Since the intestinal cells metabolize 5-FU to more polar compounds and active absorption is inhibited in a competitive manner by related compounds, these results may provide an explanation for the variable oral activity reported for 5-FU. 相似文献
212.
L R Witherspoon S E Shuler G F Joseph E F Baird H R Neely R E Sonnemaker 《Clinical chemistry》1992,38(6):887-894
We examined calibration and accuracy, precision, sensitivity, specificity, and "hook" effects for recently revised automated choriogonadotropin (hCG) immunoassay systems (Baxter-Dade Stratus II, Abbott IMx intact hCG and total beta hCG) and compared them with a widely used immunoradiometric assay (Hybritech). We estimated hCG in pregnant women, women with trophoblastic disease, nonpregnant young and menopausal women, normal men, and men with testicular tumors. We found clinically unimportant differences in calibration (all calibrated to the 3rd International Standard). Detection of hCG by all four assays was limited by their responses in serum from nonpregnant women and men. Precision within-run was best for the automated instruments, but all four assays had similar between-run precision. The Hybritech, Stratus, and IMx intact assays are specific for intact hCG. The IMx total beta assay quantifies both free beta subunit and beta subunit present in intact hCG. There is a clinically important hook effect in the Hybritech assay but not the Stratus or IMx assays (to 1.2 x 10(6) int. units/L). Results for pregnant women were similar by all four assays. We measured "hCG" to 8 int. units/L in menopausal women, which weakly correlated with concentrations of lutropin and follitropin and was, in part, explained by crossreactivity. There was no sample-probe carryover in either instrument. We found the IMx diluting module as well as results at the extremes of the IMx calibration curves (less than 10, 800-1200 int. units/L) unreliable but encountered no such problems with the Stratus system. Both automated systems involve batch analyzers with limited throughput but provide hCG concentration estimates much more quickly than the Hybritech assay can. 相似文献
213.
Norman Tinanoff Mary A. Manwell Ricki L. Zameck Joseph E. Grasso 《Journal of clinical periodontology》1989,16(5):284-290
61 adults, with fixed or removable dental protheses, completed a 6-month double-blind trial comparing the clinical and microbial effects of brushing twice daily with either 0.22% NaF or 0.4% SnF2. Those subjects brushing with SnF2 had less gingivitis and fewer bleeding sites for both "total teeth" and "abutment teeth". Plaque scores between groups were only statistically different for the "abutment teeth". The microbial parameters, salivary S. mutans and subgingival plaque total CFU, were significantly reduced in the SnF2 group. In both treatment groups, there was a reduction over the course of the study in the number of subjects with recoverable A. actinomycetemcomitans and black pigmented bacteroides, yet there was no difference between groups. 相似文献
214.
The authors examined reports addressing the question of whether electroconvulsive therapy (ECT) is more effective in psychotic or nonpsychotic depressive disorders. Most ECT studies did not consider the issue directly, and those that did had varying methodologies and results. The authors then analyzed the data of 33 depressed patients to clarify the differential response to ECT in 13 psychotic and 20 nonpsychotic patients. The subjects were also examined as to type of electrode placement. ECT produced a greater reduction in Hamilton Depression Rating Scale scores in the psychotic depressives as compared to the nonpsychotics after an average of 9.2 treatments. The two patients who were nonresponders to ECT were both nonpsychotic. 相似文献
215.
Famotidine and selected H2-antagonists were evaluated with respect to toxicity and selected pharmacological activities. When administered intraperitoneally to mice at a dose equivalent to 10 times their respective H2-antagonist ED50 values, no deaths were observed. Similarly, no alteration in brain ACh concentrations or overt pharmacological effects were noted. However, at 400 mg/kg, ranitidine produced 89% lethality, followed by cimetidine (11%) and famotidine. Only cimetidine and famotidine at this dose significantly elevated brain acetylcholine levels. These results do not correlate with the in vitro data, where ORF-17578 and ranitidine were the most potent entities with respect to acetylcholinesterase inhibition (1–2 × 10–6
M), followed by nizatidine > cimetidine > famotidine. The sulfoxide metabolites of ranitidine and cimetidine were approximately one-tenth as potent as their parent compounds with respect to inhibition of acetylcholinesterase. Direct muscarinic stimulation or potentiation of acetylcholine-induced contraction in ileal tissue was not observed for any of the H2-antagonists. 相似文献
216.
217.
Immunosuppression with cis-Platinum (II) Diammino-dichloride: Effect on Antibody Plaque-Forming Spleen Cells 下载免费PDF全文
A new antitumor compound, cis-platinum (II) diamminodichloride, suppressed antibody plaque-forming cells in C(3)H mice when given in a single dose of 10 mg per kg of body weight within 2 days before or after sensitization. 相似文献
218.
Napolitano LA Burt TD Bacchetti P Barrón Y French AL Kovacs A Anastos K Young M McCune JM Greenblatt RM 《Journal of acquired immune deficiency syndromes (1999)》2005,40(5):581-584
Sex-based differences in CD4 T-cell (CD4) counts are well recognized, but the basis for these differences has not been identified. Conceivably, homeostatic factors may play a role in this process by regulating T-cell maintenance and repletion. Interleukin (IL)-7 is essential for normal T-cell production and homeostasis. We hypothesized that differences in IL-7 might contribute to sex-based differences in CD4 counts. Circulating IL-7 levels were analyzed in 299 HIV-1-infected women and men. Regression analysis estimated that IL-7 levels were 40% higher in women than in men (P = 0.0032) after controlling for CD4 count, age, and race. Given the important role of IL-7 in T-cell development and homeostasis, these findings suggest that higher IL-7 levels may contribute to higher CD4 counts in women. 相似文献
219.
Despite evidence of an interaction between cannabinoids and estrogen in the brain, little information is available regarding the consequences of this interaction on behavior. A within-subjects design was used to examine the effects of estrogen and delta9-tetrahydrocannabinol (delta9-THC) on learning and memory in ovariectomized rats responding under a multiple schedule of repeated acquisition and performance. Treatment with low physiological levels of estrogen, delivered in Silastic capsules, improved response accuracy without affecting response rate during acquisition. Estrogen also attenuated the ability of delta9-THC (0.56- 3.2 mg/kg) to decrease response accuracy and rate during acquisition and response accuracy during performance. Results indicate that estrogen can improve accuracy during acquisition of a nonspatial operant task and can attenuate delta9-THC- induced behavioral deficits. 相似文献
220.
Chitti R. Moorthy J. Rao Nibhanupudy Ebrahim Ashayeri Alfred L. Goldson Maria C. Espinoza Joseph J. Nidiry Oswald G. Warner Vincent J. Roux 《Journal of the National Medical Association》1982,74(3):261-266
The objective of radiotherapeutic management in esophageal cancer is to accomplish maximum tumor sterilization with minimal normal tissue damage. This sincere effort is most often countered by the differential in tumor dose response vs normal tissue tolerance. Intraluminal isotope radiation, with its inherent advantage of rapid dose falloff, spares the lungs, the spinal cord, and other vital structures, yet yields adequately high doses to esophageal tumor. Though in existence since the turn of the century, the method of intracavitary radium bougie application dropped out of favor due to technical difficulties imposed by the size of the radium source and radiation exposure to the personnel involved. The authors describe a simple “iridium 192 afterloading intraluminal technique” that eliminates technical problems and reduces radiation exposure considerably. 相似文献