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61.
62.
2-(1-Aryl-1-hydroxymethyl)- and 2-aroyl-DHAQ derivatives (DHAQ, 1,4-dihydroxy-9,10-anthraquinone), and 2-(1-aryl-1-hydroxymethyl)-ATO derivatives (ATO, anthracene-1,4,9,10-tetraone) were synthesized and their antitumor activities were determined. 2-(1-Aryl-1-hydroxymethyl)-DHAQ derivatives showed a stronger cytotoxicity compared to the series of 2-(1-hydroxyalkyl)-1,4-dihydroxy-9,10-anthraquinone derivatives. It was suggested that the presence of aryl group at the side chain accelerated the bioreductive activation leading to cell death. 2-Aroyl-DHAQ derivatives, despite their higher electrophilicity, revealed smaller cytotoxicity and antitumor activity (expressed by T/C value) than 2-(1-aryl-1-hydroxymethyl)-DHAQ derivatives. Thus, no consistent relationship between the electronic effect on aromatic side chain and the cytotoxicity was observed. ATO series exhibited a higher antitumor activity (T/C, 125 to approximately 218%), though their cytotoxicity was not further improved compared to that of 2-(1-aryl-1-hydroxymethyl)-1,4-dihydroxy-9,10-anthraquinones. They manifested no correlation between the cytotoxicity and the antitumor activity. In case of 2-[1-hydroxy-1-(4-propylphenyl)-methyl]-ATO, the most bioactive one in vivo among the same series, it showed an ED50 value of 10.2 mg/mL and a T/C value of 218%. It is assumed that the anthracene-1,4,9,10-tetraones after uptake into cellular tissues might be transformed to a cytotoxic metabolite(s). 相似文献
63.
Dirk H. G. Versteeg Tamás Csikós Henk Spierenburg 《Naunyn-Schmiedeberg's archives of pharmacology》1991,343(6):595-602
Summary The periaqueductal gray is a brain region of considerable interest. It is innervated by monoamine-containing neurons as well as by a variety of peptidergic fiber systems, and it participates in the regulation of various functions. Virtually nothing is known about monoamine release in the periaqueductal gray and its receptor-mediated modulation. We therefore studied the release of radioactivity from periaqueductal gray slices preloaded with tritriated monoamines, using an in vitro superfusion method.The release of radioactivity from superfused periaqueductal gray slices after preloading of the tissue with [3H]noradrenaline increased upon electrical stimulation in a frequency-dependent manner. The stimulus-evoked release of radioactivity was Ca2+-dependent. Clonidine reduced and yohimbine enhanced the release. The inhibition curve for the effect of clonidine was shifted to the right in the presence of 10–6 M yohimbine. While phenylephrine, isoprenaline, SK&F 38393, quinpirole, carbachol, [Arg8]vasopressin, -MSH and ACTH-(1-24), at a concentration of 10–6 M, did not influence the electrically evoked release of radioactivity, [Leu5]enkephalin reduced it. The selective -opioid receptor agonists [d-Ala2,NMePhe4,Gly-ol5]enkephalin and [d-Arg2,Lys4]-dermorphin-(1–4)-amide reduced the release of radioactivity, whereas the selective opioid receptor agonist [d-Pen2,d-Pen5]enkephalin and the selective K opioid receptor agonist U-69593 had no effect. In the presence of naloxone, which by itself had no effect on the release of radioactivity, the effect of [d-Arg2,Lys4]dermorphin-(1–4)-amide was abolished. These results show that the release of noradrenaline from periaqueductal gray slices is via a Ca2+-dependent. exocytotic process, and that it is modulated through 2-adrenoceptors as well as via -opioid receptors. Though the overflow of radioactivity from slices preloaded with [3H]dopamine in the presence of desipramine was measurable, there are reasons to assume that we are dealing here with the release of tritiated catecholamines from a population of nerve endings consisting of noradrenergic and dopaminergic terminals.The release of radioactivity from periaqueductal gray slices preloaded with [3H]5-hydroxytryptamine upon elevation of the K+ concentration in the superfusion medium was much more pronounced than that induced by electrical stimulation. The K+-evoked release of radioactivity was almost completely abolished in the absence of Cat2+; showing that the release is via a Ca2+-dependent process. 5-Hydrotryptamine reduced the K+-evoked release of radioactivity in a concentration-dependent manner.Some of these data were presented at the XIth International Congress of Pharmacology, 1–6 July 1990, Amsterdam, The Netherlands (Eur J Pharmacol 183:408)
Send offprint requests to D. H. G. Versteeg at the above address 相似文献
64.
Nancy Young MD Tam Nguyen MD Richard Wiet MD FACS 《Operative Techniques in Otolaryngology》2003,14(4):263-267
Cochlear implants are the single greatest advancement of the late 20th century for the deaf and hearing impaired. Recent expanding guidelines as well as surgical techniques are discussed. Cochlear implantation is currently the only means to restoring partial hearing to patients with severe-to-profound sensorineural loss not aidable with conventional amplification. 相似文献
65.
Abstract: The proximity of the α‐amine and β‐thiol of α‐amino terminal‐cysteine (NT‐Cys) residues in peptides imparts unique chemical properties that have been exploited for inter‐ and intra‐molecular ligation of unprotected peptides obtained through both synthetic and biological means. A reversible protecting group orthogonal to other protection strategies and reversible under mild conditions would be useful in simplifying the synthesis, cleavage, purification and handling of such NT‐Cys peptides. It could also be useful for the sequential ligation of peptides. To this end, we explored tri‐one chemistry and found that ninhydrin (indane‐1,2,3 trione) reacted readily with cysteine or an NT‐Cys‐containing peptide on‐ or off‐resin at pH 2–5 to form Ninhydrin‐protected Cys (Nin‐Cys) as a thiazolidine (Thz). The Thz ring, protecting both the amino and thiol groups in Nin‐Cys, completely avoids the formylation and Thz side reactions found during hydrofluoric acid (HF) cleavage when N‐π‐benzyloxymethyl histidine groups are present. Nin‐Cys is stable during coupling reactions and various cleavage conditions with trifluoroacetic acid or HF, but is deprotected under thiolytic or reducing conditions. These properties enable a facile one‐step deprotection and end‐to‐end‐cyclization reaction of Nin‐Cys peptides containing C‐terminal thioesters. 相似文献
66.
67.
S. S. Wijesinha B. L. Atkins N. E. Dudley P. K. H. Tam 《Pediatric surgery international》1998,13(2-3):146-148
A prospective study of 25 boys who underwent circumcision for medical reason was performed. Specimens of periurethral bacterial
flora were taken before operation as well as 3 weeks after surgery, so that each boy acted as his own control. Before circumcision,
13 (52%) harboured uropathogenic organisms (Escherichia coli and other coliforms, Enterococcus spp, Proteus spp, Pseudomonas spp, and Klebsiella spp); after circumcision, none of the boys had uropathogens, the only organisms cultured from the periurethral region being
skin commensals. We postulate that circumcision converts a ‘cul-de-sac' that is a reservoir of organisms capable of causing
ascending urinary tract infection into a surface colonised by natural skin organisms. This study provides circumstantial evidence
supporting the idea that circumcision in well-selected patients may confer protection from urine infection.
Accepted: 15 March 1997 相似文献
68.
Gábor RÉPÁssy Csaba Forster-HorvÁth Attila JuhÁsz Róza ÁDÁny Anna TamÁssy József TÍmÁr 《Pathology oncology research : POR》1998,4(1):14-21
Twelve laryngeal squamous cell carcinoma cases (7 laryngeal and 5 hypopharyngeal cancer; 15 samples) were analysed by immunohistochemistry
for the expression of invasion markers CD44v6/v3, NM23 and matrix metalloproteinase, MMP2. The laryngeal epithelium showed
CD44v6+v3+NM23- /MMP2- phenotype. When tumors were grouped into TNM categories the phenotype of the T2 and T3 tumors was similar, characterised
by decreased CD44v3+ and lack of MMP2 expressions. Meanwhile the NM23 expression was more frequent in T3 tumors. In T4 stage the frequency of
NM23 and MMP2 positive cases increased (5/6 and 4/6, respectively) but there was no correlation with the appearence of lymph
node metastasis. Comparison of the phenotype of laryngeal and hypopharyngeal tumors, irrespective of the TNM stages, revealed
characteristic differences: T2 stage laryngeal tumors showed decreased CD44v3 and occasional NM23 and MMP2 positivity, while
in T3 stage these tumors were characterised by increased frequency of NM23 positivity. The phenotype of the hypopharyngeal
tumors was significantly different with a high frequency of MMP2 positive cases (5/6) and NM23+1ow CD44v3+ phenotype. The sharp differences in the phenotypes of laryngeal and hypopharyngeal carcinomas were connected to the differences
in their invasive capacity unlike to the size of the tumors, since the T4 stage hypopharyngeal tumors had a significantly
smaller size than laryngeal ones, even at lower stages.
This work was supported by the Hungarian Ministry of Welfare: ETT No: T-11-100/93 相似文献
69.
Esophageal atresia and tracheal stenosis: use of three-dimensional CT and virtual bronchoscopy in neonates, infants, and children 总被引:6,自引:0,他引:6
OBJECTIVE: The objective of this study was to evaluate the use of three-dimensional CT and virtual bronchoscopy in the treatment of neonates, infants, and children with esophageal atresia and tracheal stenosis. CONCLUSION: Long-gap (n = 1) and short-gap (n = 5) esophageal atresia, long-segment stenosis (n = 2), patent poststenting trachea (n = 1), normal trachea without fistula (n = 1), and tracheal bronchus (n = 1) were studied. Fistulas between the lower esophagus and carina were noted in all six cases of esophageal atresia. All CT findings correlated with operative or bronchoscopy findings. Sensitivity and specificity were 100%. Three-dimensional CT and virtual bronchoscopy are accurate and useful techniques in the preoperative assessment of esophageal atresia and tracheal stenosis in neonates, infants, and children. 相似文献
70.