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MARINA GOBBO LAURA BIONDI FERNANDO FILIRA TOM PIEK RANIERO ROCCHI 《Chemical biology & drug design》1995,45(5):459-465
Syntheses are described of the endo-Lys8a-vespulakinin 1 and of cyclo-Thr6- and cyclo-Nε-Lys-bradykinin. The linear peptides covering the entire sequences of endo-Lys8a-VSK-1 and Thr6-BK, and the decapeptide containing all residues constituting Lys-BK, with a Arg-Lys peptide bond involving the ε-amino function of lysine, were prepared by the solid-phase procedure based on Fmoc chemistry. Cyclization was carried out by the diphenylphosphorazide method. The amino-terminal octapeptide sequence of vespulakinin 1, Fmoc-Thr(tBu)-Ala-Thr(tBu)-Thr(tBu)-Arg(Pmc)-Arg(Pmc)-Arg(Pmc)-Gly-OH, and its Nα-Boc-[(Gal β)Thr3, (Gal β)Thr4]-analogue, were used to prepare Nα-(1–8 VSK 1)-cyclo-Nε-kallidin and Nα-[(Gal β)Thr3, (Gal β)Thr4, 1–8 VSK 1]-cyclo-Nε-kallidin. Peptides and glycopeptides were characterized by amino-acid analysis, optical rotation, analytical HPLC and FAB-MS. Consistent with previous findings, preliminary pharmacological experiments on smooth muscle preparations showed that the cyclic, or partially cyclic, analogues were significatively less potent than the linear ones. © Munksgaard 1995. 相似文献
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BACKGROUND: In the area of endovenous chemical ablation (sclerotherapy), there has been much debate regarding sclerosant quality and efficacy. Only sodium tetradecyl sulfate (STS) has garnered Food and Drug Administration (FDA) approval in the United States. OBJECTIVE: The primary objective of this study was to compare clinical performance measures of compounded STS from 27% industrial-strength stock (compounded STS) versus FDA-approved Sotradecol (Bioniche Pharma USA, Inc., Belleville, Ontario, Canada). MATERIALS AND METHODS: Phase I of this study focused on the chemical composition of the drugs, whereas Phase II studied the ablative abilities of the two drugs at comparable concentrations of 3%. RESULTS: We documented the presence of various impurities in compounded STS. No impurities in AngioDynamics STS were found. Our studies suggest that compounded STS may have significant variation in concentration. The AngioDynamics STS concentration was found to be manufactured within a tight tolerance. Segments of incomplete ablation were more frequent in the compounded STS group when compared to the AngioDynamics STS group. This reached statistical significance (p=.02). Primary closure using the Kaplan-Meier statistic demonstrated a trend in the favor of AngioDynamics STS when compared to compounded STS. CONCLUSION: When product quality, efficacy, and liability are carefully considered, we conclude that it would behoove physicians to use pharmaceutical-grade, FDA-approved sclerosant when treating their patients. 相似文献
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The Effect of Completeness of Medical Records on the Determination of Appropriateness of Hospital Days 总被引:1,自引:1,他引:0
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Protection against Acetaminophen Hepatotoxicity by a Single Dose of Clofibrate: Effects on Selective Protein Arylation and Glutathione Depletion 总被引:5,自引:4,他引:1
MANAUTOU JOSE E.; HART SUSAN G. EMEIGH; KHAIRALLAH EDWARD A.; COHEN STEVEN D. 《Toxicological sciences》1996,29(2):229-237
Previous reports demonstrated that repeated administration ofperoxisome proliferators protects against acetaminophen (APAP)hepatotoxicity in mice. This protection was associated witha decrease in APAP's selective protein arylation and glutathionedepletion. This study was conducted to determine if a singledose of clofibrate (CFB), rather than repeated doses, wouldsimilarly prevent APAP toxicity. CD-1 male mice received a singledose of 500 mg CFB/kg and controls were given corn oil 24 hrprior to APAP challenge. After an 18-hr fast, mice were challengedwith 800 mg APAP/kg (in 50% propylene glycol) and killed at4 or 12 hr. Other mice similarly pretreated were killed withoutAPAP challenge. The results showed that pretreatment with asingle CFB dose significantly decreased APAP-induced hepatotoxicity.At 12 hr after APAP plasma sorbitol dehydrogenase activity andthe severity of hepatocellular necrosis were decreased in CFBpretreated mice. Surprisingly, no differences in hepatic nonproteinsulfhydryl (NPSH) depletion or selective arylation of targetproteins in cytosol were observed at 4 hr after APAP challenge.Neither did a single dose of CFB significantly alter hepaticNPSH content prior to APAP challenge. These results indicatethat protection against APAP hepatotoxicity by CFB does notrequire repeated administration, and the absence of significantalterations in APAP's selective protein arylation or glutathionedepletion suggests that the protection against APAP hepatotoxicityafter a single treatment with CFB may differ mechanisticallyfrom the protection observed after repeted CFB dosing. 相似文献
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His‐Bundle Pacing for Identifying Optimal Ablation Sites in Patients Undergoing Atrioventricular Junction Ablation 下载免费PDF全文
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