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1.
E Pop W Anderson K Prókai-Tátrai M E Brewster M Fregly N Bodor 《Journal of medicinal chemistry》1990,33(8):2216-2221
The essential amino acid, tryptophan, has been shown to lower blood pressure in rats when administered orally or intravenously. In order to potentially enhance this action, a brain-targeting chemical delivery system (CDS) approach was applied to this compound. The CDS is based on a dihydropyridine----pyridinium ion redox system, chemically analogous to the naturally occurring NADH----NAD+ system. The dihydropyridine moiety containing carrier is chemically attached to the amino group by an amide-type bonding while the carboxylic acid functionality is esterified to various alcohols. Physicochemical studies of the new derivatives were performed. The determined chromatographic Rm values indicate an increased lipophilicity for the CDSs compared to the parent compound. Oxidation stability studies performed on selected compounds using a ferricyanide-mediated method showed that the CDSs are oxidized to the respective quaternary salt forms. Activity studies performed in deoxycorticosterone acetate induced hypertensive rats, demonstrated that the delivery system for tryptophan reduced blood pressure more efficiently for a longer time than did the parent compound. 相似文献
2.
K Niedzielska W Laskowska-Studniarska J Kunicka W Pop?awska W Kuran K Witkowska-Olearska 《Neurologia i neurochirurgia polska》1992,26(4):450-457
In 24 patients with diagnostically not clear, short, recurrent episodes of consciousness disturbances and heart diseases and/or a history of arrhythmia simultaneous 24-hour recording was done of eeg and ecg. In the differential diagnosis epilepsy was considered, especially since in most cases routine eeg records demonstrated slight episodic changes. During 24-hour recording in 8 cases typical episodes of consciousness disturbances developed but in none of them these episodes were associated with arrhythmia which ruled out their cardiogenic origin. In 2 cases EEG recording served for establishing the diagnosis of partial complex seizures, 2 patients had hyperventilation syncope, one had TIA, in the remaining 3 cases absence of eeg and ecg changes during these episodes and coexistence of anxiety neurosis suggested functional origin. So the combined 24-hour eeg+ecg recording made possible establishing of diagnosis in 1/3 of these patients, enabling adequate treatment to be instituted. 相似文献
3.
Internalization of sst2, sst3, and sst5 receptors: effects of somatostatin agonists and antagonists. 总被引:4,自引:0,他引:4
Renzo Cescato Stefan Schulz Beatrice Waser Véronique Eltschinger Jean E Rivier Hans-Jürgen Wester Michael Culler Mihaela Ginj Qisheng Liu Agnes Schonbrunn Jean Claude Reubi 《Journal of nuclear medicine》2006,47(3):502-511
The uptake of radiolabeled somatostatin analogs by tumor cells through receptor-mediated internalization is a critical process for the in vivo targeting of tumoral somatostatin receptors. In the present study, the somatostatin receptor internalization induced by a variety of somatostatin analogs was measured with new immunocytochemical methods that allow characterization of trafficking of the somatostatin receptor subtype 2 (sst2), somatostatin receptor subtype 3 (sst3), and somatostatin receptor subtype 5 (sst5) in vitro at the protein level. METHODS: Human embryonic kidney 293 (HEK293) cells expressing the sst2, sst3, or the sst5 were used in a morphologic immunocytochemical internalization assay using specific sst2, sst3 and sst5 antibodies to qualitatively and quantitatively determine the capability of somatostatin agonists or antagonists to induce somatostatin receptor internalization. In addition, the internalization properties of a selection of these agonists have been compared and quantified in sst2-expressing CHO-K1 cells using an ELISA. RESULTS: Agonists with a high sst2-binding affinity were able to induce sst2 internalization in the HEK293 and CHO-K1 cell lines. New sst2 agonists, such as Y-DOTA-TATE, Y-DOTA-NOC, Lu-DOTA-BOC-ATE (where DOTA is 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid; TATE is [Tyr3, Thr8]-octreotide; NOC is [1-NaI3]-octreotide; and BOC-ATE is [BzThi3, Thr8]-octreotide), iodinated sugar-containing octreotide analogs, or BIM-23244 were considerably more potent in internalizing sst2 than was DTPA-octreotide (where DTPA is diethylenetriaminepentaacetic acid). Similarly, compounds with high sst3 affinity such as KE108 were able to induce sst3 internalization. In sst2- or sst3-expressing cell lines, agonist-induced receptor internalization was efficiently abolished by sst2- or sst3-selective antagonists, respectively. Antagonists alone had no effect on sst2 or sst3 internalization. We also showed that somatostatin-28 and somatostatin-14 can induce sst5 internalization. Unexpectedly, however, potent sst5 agonists such as KE108, BIM-23244, and L-817,818 were not able to induce sst5 internalization under the same conditions. CONCLUSION: Using sensitive and reproducible immunocytochemical methods, the ability of various somatostatin analogs to induce sst2, sst3, and sst5 internalization has been qualitatively and quantitatively determined. Whereas all agonists triggered sst2 and sst3 internalization, sst5 internalization was induced by natural somatostatin peptides but not by synthetic high-affinity sst5 agonists. Such assays will be of considerable help for the future characterization of ligands foreseen for nuclear medicine applications. 相似文献
4.
In most textbooks of gastroenterology, diseases with their symptoms are discussed. The exact diagnostic value of these symptoms, however, regarding the differentiation between organic and functional disease, is not mentioned. A criteria-based meta-analysis of the few existing studies in this field was done. From the 14 identified studies, there were two that did not find any significant symptoms. In the other studies the diagnostic value of colonic symptoms showed great variability. Methodological deficiencies in these studies are probably responsible for the latter. The generalization of these results into general practice is not straightforward and needs research in general practice patients. 相似文献
5.
Six chemical delivery systems (CDS) were synthesized for benzylpenicillin in order to improve its transport across the blood-brain barrier. The CDS's were based on a dihydropyridine----quaternary pyridinium ion redox system, analogous to the naturally occurring NADH----NAD+ system. Two different types of CDS's were prepared: benzylpenicillin esters of diols in which the other hydroxyl group is esterified by dihydrotrigonelline and benzylpenicillin esters of amino alcohols in which the amine group is acylated by dihydrotrigonelline, or by 1,2-dihydro-2-methyl-4-isoquinolinecarboxylic acid. Lipophilicities of the CDS's were proved to be much higher than those of benzylpenicillin by using Rm values as lipophilicity indexes. Upon oxidation, all of the CDS's gave the quaternary ion forms. Kinetic studies in buffer (pH profiles) indicated that the quaternary salts released benzylpenicillin in pH range of 5-9 via hydrolysis. The CDS's in acidic media yielded as the major reaction product 6-hydroxy-1,4,5,6-tetrahydropyridines as a result of water addition, while in basic conditions benzylpenicillin was released. The water addition reaction was dependent on the CDS's structure, being more prevalent in the case of the "amide-esters". The dihydroisoquinoline CDS was rather stable in the pH range 5-8. 相似文献
6.
7.
8.
OBJECTIVES: It is suggested that during menopausal transition, women with vasomotor symptoms benefit from HRT, (hormone replacement therapy) whereas, the use of HRT for other cognitive-vegetative symptoms is questionable. METHODS: The occurrence of menopausal complaints and depressive symptoms was assessed cross-sectionally in 5896 Dutch Caucasian women (47-54 years) of a large community sample in the city of Eindhoven, The Netherlands. Menopausal complaints were assessed using a 22 items self-rating scale (consisting of a vasomotor, uro-genital and a cognitive-vegetative subscale). Depressive symptoms were assessed using the Edinburgh depression scale (EDS). Differences in mean scores were analysed between groups using ANOVA. The independent relationship of depressive symptoms to the intensity of menopausal complaints was assessed, by multiple linear regression analysis. RESULTS: Women using HRT showed the highest scores on all subscales. Oral contraceptive users had significantly lower scores on the vasomotor subscale compared to HRT users and to non users. Depressive symptoms contributed the most, to the explained variance on scores on the menopausal subscales. CONCLUSIONS: Women during menopause presenting several complaints, other than vasomotor origin might be suffering from underlying depression which makes it questionable to prescribe HRT for the latter symptoms. 相似文献
9.
10.
PURPOSE: To study photorefractive keratectomy (PRK) for high myopia using the Nidek EC-5000 slit scanning laser and to compare a single pass versus a multipass ablation approach. METHODS: We retrospectively studied 95 eyes (64 patients; range -10.00 to -27.00 D; mean -12.00 D) treated for high myopia using PRK with a single or multipass technique. Forty-two eyes were treated with the single pass technique and 53 eyes were treated with the multipass technique. RESULTS: Twelve months after PRK, 79.4% (27 eyes) of the multipass group and 48.1% (13 eyes) of the single pass group were within +/-1.00 D of emmetropia; 32.4% (11 eyes) of multipass eyes and 29.6% (8 eyes) of single pass eyes were within +/-0.50 D of emmetropia. Uncorrected visual acuity of 20/40 or better was reached by 85.3% (29 eyes) and 20/20 or better was reached by 55.9% (19 eyes) in the multipass group at 12 months postoperatively. For the single pass group, 74.1% (20 eyes) achieved 20/40 uncorrected and 18.5% (5 eyes) achieved 20/20 uncorrected visual acuity. No multipass-treated eyes lost 2 lines of spectacle-corrected visual acuity at 6 or 12 months postoperatively. Mean regression between 1 to 12 months after PRK was 0.46 D for the multipass group and 1.45 D for the single pass group. Most of the regression occurred within the first 6 months after surgery in both techniques. CONCLUSION: These PRK results showed that treating high myopia using the Nidek EC-5000 excimer laser combined with a multipass approach generated good refractive outcomes with no complications. Undercorrections with the single pass technique could be compensated for with new nomograms. The multipass technique resulted in less regression and better refractive outcomes. 相似文献