Polyacetylenes from the Underground Parts of Cichorium intybus.
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Biomedical subjects
Publications and source records attributed to G Rücker.
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From the leaves of BLUMEA ARFAKIANA Martelli (Asteraceae), used in traditional medicine in Papua New Guinea, besides stigmasterol and beta-eudesmol, four graniline esters ( 1-4) have been isolated. Furthermore, blumealactone C ( 5), deacetylblumealactone C ( 6), and deoxyblumealactone C ( 7) have been identified.
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From the chinese drug "Daxueteng" (Caulis Sargentodoxae: Sargentodoxa cuneata (Oliv.) Rehd. et Wils.; syn. Holboellia cuneata Oliv.) (Sargentodoxaceae), catechin and two known triterpene saponins, rosamultin (7) and kajiichigoside F1 (8) have been isolated. Some hitherto unknown reaction products of the saponins are described. Both 7 and 8 show haemolytic and in vitro antiviral activity.
Yarrow, Achillea millefolium L., is one of the commonest weeds of the Compositae family. Cases of allergic contact dermatitis have been described since 1899. Although 10 sesquiterpene lactones (SL) and 3 polyines have previously been identified, the sensitizers of yarrow have escaped detection. A reinvestigation of short ether extracts of yarrow revealed the presence of 5 unsaturated hitherto unknown guaianolides of peroxide character. The main SL, identified as a strong sensitizer in guinea pig sensitization experiments, was named alpha-peroxyachifolid. The minor SL also contribute marginally to the sensitizing capacity, while other known yarrow constituents like dehydromatricaria ester and pontica epoxide appear to play no role. A 5-year follow-up (1985-1990) of Compositae-sensitive patients showed that more than 50% reacted when tested with a short ether extract of yarrow. Exacerbation of the patch test sites by irradiation with UV light was never observed.
From the ether extract of the blossoms of yarrow, Achillea millefolium L., two guaianolides (1, 2) with a peroxide bridged cyclopentane ring and an alpha-methylene-gamma-butyrolactone structure have been isolated. For these compounds the names alpha-peroxyachifolid (1) and beta-peroxyisoachifolid (2) are proposed. 1 is responsible for the allergic contact dermatitis caused by yarrow.
A spectrodensitometric method is described for the determination of the components of two analgesic mixtures. For the first mixture (paracetamol-ascorbic acid-caffeine-phenylephrine), the pharmaceutically active components were separated from each other and closely related degradation products and impurities on high-performance thin-layer chromatography (F254) plates using methylene chloride-ethyl acetate-ethanol-formic acid (3.5 + 2 + 4 + 0.5) and methylene chloride-ethyl acetate-ethanol (5 + 5 + 1) as the developing systems. The other mixture (phenazone-phenacetin-caffeine) was separated efficiently from the degradation products using the same plates and acetonitrile-chloroform (1 + 1) as the mobile phase. The proposed method was used to determine these mixtures in commercial tablets.
From the ethanol extract of the blossoms of Anthemis nobilis L. (syn. Chamaemelum nobile L.), six new hydroperoxides (1-6) were isolated, besides the known 1 beta-hydroperoxyisonobilin (7). The structures were elucidated by spectroscopic methods and in some cases ascertained by synthesis. Compounds 2 and 3 show a medium antibacterial activity.
We propose a two-stage randomized clinical trial design for separating treatment effects from those resulting from choosing treatment. At the first stage all patients are randomly allocated to one of two groups, the random group and the option group. At the second stage, patients in the random group are randomized a second time to treatment A or B, whereas patients in the option group are given a free choice between the two treatments. If there are differences in treatment response between the random group and the option group, there are two potential sources of bias: self-selection by choosing treatment, and effects of suggestion by receiving the preferred treatment. A linear model is presented to estimate these effects separately along with test statistics which are approximately normally distributed.
Remission duration data from two observational studies, the German ALL/AUL study on acute lymphoblastic and acute undifferentiated leukaemia and the Kiel Lymphoma Study, are used to demonstrate the adequacy of an interval-censoring approach. The Turnbull estimator is contrasted with the conventionally used Kaplan-Meier estimator. In addition, a parametric model is used for estimation or simulation of the delay times of complete remission diagnosis and relapse diagnosis. Two possible consequences of the conventional approach are discussed: biased estimation (for example, overestimation of remission duration), and underestimation of the true error variance, which may lead to false positive results. On the other hand, the applicability of the interval-censoring approach is doubtful when the censoring mechanism (examination pattern, patient's behaviour) is confounded with the endpoints.
After oral administration of 1-[(4-chlorophenyl)-phenylmethyl]-4-[3-methylphenyl)-methyl]-piperazine (1, Meclozine) eleven compounds were isolated from human urine and faeces. The structural elucidation of the metabolites was accomplished by comparison of their spectral data with those of the synthetic reference compounds. The metabolites were identified as: Meclozine (1), N-[(4-chlorophenyl)-phenylmethyl]-piperazine (2), 3-(4-[(4-chlorophenyl)-phenylmethyl]-piperazino)-methyl-benzoic acid (3), 3-(4-[(4-chlorophenyl)-phenylmethyl]-piperazino)-methyl-benzamide] (4), 2-[3-(4-[(4-chlorophenyl)-phenylmethyl]-piperazino)-methyl-benzoyl ]-amino- ethanesulphonic acid (5), 3-(4-[(4-chlorophenyl)-3'-hydroxy-4'-methoxyphenylmethyl]-piper azino)- methyl-benzoic acid (6), 1-[(4-chlorophenyl)-phenylmethyl]-4-[(3-methylphenyl)-methyl]- piperazine-N4-oxide (7), 1-[(4-chlorophenyl)-phenylmethyl]-4-[(3-methylphenyl)-methyl]- piperazine-N,N'-dioxide (8), 3-methyl-benzoic acid (9), 3-methyl-hippuric acid (10) and 3-methyl-benzoic acid-glucuronide (11). The structure of compound 11 was confirmed after enzymatic cleavage and identification of the aglycon. A further metabolite was detected, but not identified.
After oral administration of 3,7-dihydro-1,3-dimethyl-7-2 [(1-methyl-2-phenylethyl)-amino-ethyl]-1H-purine-2,6-dione (fenetylline, Captagon), 7 new metabolites could be detected in urine besides 4 known substances. The metabolites were identified by gas chromatography (GC) and by comparison of the mass spectra (MS) of metabolites with those of authentic reference compounds using a combined GC/MS method.
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After the administration of chlorphenoxamine (2-[1-(4-chlorophenyl)-1-phenylethoxy]-N,N-dimethylethanamine++ +, Systral) (I) the following compounds have been detected in human urine. They were identified as chlorphenoxamine (I), N-demethyl-chlorphenoxamine (II), chlorphenoxamine-N-oxide (III), 1-(4-chlorophenyl)-l-phenylethanol (IV), 1-(4-chlorophenyl)-1-(4'-hydroxyphenyl)-ethanol (V), 1-(4-chlorophenyl)-1-(4'-hydroxyphenyl)-ethene (VI), 1-(4-chlorophenyl)-1-(4'-hydroxy-3'-methoxyphenyl)-ethanol (VII), 1-(4-chlorophenyl)-1-(4'-hydroxy-3'-methoxyphenyl)-ethene (VIII), 2-[1-(4-chlorophenyl)-1-(4'-hydroxyphenyl)-ethoxy]-N-methyl-ethanamine (IX) and 2-[1-(4-chlorophenyl)-1-(4'-hydroxy-3'-methoxyphenyl-ethoxy]- N-methylethanamine (X). The compounds IV, V, VI, VII, VIII, IX and X were also found to be excreted as conjugates. It cannot be excluded that the compounds VI and VIII are artefacts.
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The behaviour of 2-phenyl-1-propanol (I) and 2-phenyl-2-propanol (II) and their glucuronides with HCl has been investigated. While I shows a high acidic constancy, II undergoes a partial conversion into 2-phenylpropane (III) which itself yields numerous products. The glucosidic bond of glucuronide I is quantitatively split by 10.0% HCl, whereby an aglucone yield of nearly 100% is obtained. The second glucuronide behaves otherwise: the recovery of II is very low (only 40% to 45%) with HCl concentrations of 1.0%-20.0%, although with 1.0% HCl 100% of the glucuronide is hydrolysed.
It has been reported before that pentazocine (I) and pentazocine-glucuronide (II) form an artifact (III) by the addition of water to the double bond in the presence of HCl. This reaction leads to different results concerning the investigation of the rate of hydrolysis of II and the recovery of I. The glucuronide was quantitatively hydrolyzed by 20% HCl, but yielded only 15% of I (about 64% was detected as III). With 5% HCl the rate of hydrolysis only amounted to 40%-43%, whereas I yielded 31% (only 9% was recovered as III). The best III yield was obtained with a HCl concentration of 17.5%.
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