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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Archives of gynecology and obstetrics 91 (1910), S. 214-225 
    ISSN: 1432-0711
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-072X
    Keywords: Guaiacylglycerol-β-coniferyl ether ; Lignin biodegradation ; Fusarium solani ; Guaiacylglycerol-β-coniferyl aldehyde ether ; Guaiacylglycerol-β-ferulic acid ether ; Guaiacylglycerol-β-vanillin ether ; Guaiacylglycerol-β-vanillic acid ehter ; erythro form ; threo form
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Fusarium solani M-13-1 was shake-cultured in a medium containing guaiacylglycerol-β-coniferyl ether (I), a model compound representing the arylglycerol-β-aryl ether linkage in lignin, as sole carbon source. From the culture filtrate guaiacylglycerol-β-coniferyl aldehyde ether (II) and guaiacylglycerol-β-ferulic acid ether (III) were isolated as metabolic products. Incubation with (III) resulted in formation of guaiacylglycerol-β-vanillin ether (IV), which was further metabolized to guaiacyglycerol-β-vanillic acid ether (V). The results indicate that the cinnamyl alcohol group of (I) is initially oxidized to an aldehyde group, which is further oxidized to a carboxyl group, yielding (II) and (III). Compound (III) is converted to (IV) by the release of a C2 fragment, and the aldehyde group of (IV) is further oxidized to a carboxyl group, giving (V). In the pathway from (I) to (V), neither oxidation of the benzylic secondary alcohol to ketone nor cleavage of the arylglycerol-β-aryl ether linkage was observed. The fungus was found to attack both erythro and threo form without distinction.
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  • 3
    ISSN: 1432-072X
    Keywords: Lignin biodegradation ; Fusarium solani ; d,l-Syringaresinol ; Alkyl-aryl cleavage ; 2,6-Dimethoxy-p-benzoquinone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract A β-β′ linked lignin model compound, d,l-syringaresinol monobenzyl ether (Ib) was incubated with Fusarium solani M-13-1 in a shaking culture. From the culture filtrates, three compounds II, IIIb and IV were isolated and identified. Substrate Ib was oxidized at the α-position of the side chain to give a hemiketal, an α-hydroxylated compound IIA, which was then transformed to the ketoalcohol, 3-hydroxymethyl-2-(4-benzyloxy-3,5-dimethoxyphenyl)-4-(4-hydroxy-3,5-dimethoxybenzoyl)-tetrahydrofuran (IIB). These products were converted to a γ-lactone derivative, 6-oxo-2-(4-benzyloxy-3,5-dimethoxyphenyl)-3,7-dioxabicyclo-[3,3,0]-octane (IIIb), via alkyl-aryl cleavage. The syringyl moiety released from II by the cleavage reaction was identified as 2,6-dimethoxy-p-benzoquinone (IV). Incubation of 2,6-dimethoxyphenol (V) in fungal culures did not give the p-quinone IV. d,l-Syringaresinol dimethyl ether was not degraded and the etherated moiety of Ib was not attacked by the fungus, indicating that the degradation of d,l-syringaresinol was catalyzed by phenol oxidizing enzymes. The oxidation products of Ib with peroxidase/H2O2 was investigated and discussed in relation to the degradation products of the fungus.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-072X
    Keywords: White-rot fungi ; Secondary metabolism ; Wood decay ; Mycelial pellets ; Fungus physiology ; l-Glutamic acid repression ; Phenylalanine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The lignin-degrading basidiomycete Phanerochaete chrysosporium synthesizes veratryl alcohol (3,4-dimethoxybenzyl alcohol) via phenylalanine, 3,4-dimethoxycinnamyl alcohol and veratrylglycerol. Study of the conversion of 3,4-dimethoxycinnamyl alcohol to veratrylglycerol and veratryl alcohol showed is to be (a) catalyzed by a secondary metabolic system, (b) markedly suppressed by culture agitation, and (c) strongly inhibited by l-glutamate. The amount of veratryl alcohol synthesized de novo was positively correlated with the O2 concentration after primary growth. Other work has shown that the cinnamyl alcohol terminal residue in a lignin substructure model compound is degraded via arylglycerol and benzyl alcohol structures in ligninolytic cultures of P. chrysosporium, and that the ligninolytic system exhibits traits (a)-(c) above. Ligninolytic activity is also strongly and positively correlated with O2 concentration. The results here suggest, therefore, that the actual biosynthetic secondary metabolic product is 3,4-dimethoxycinnamyl alcohol, but that this is degraded by the ligninolytic system to veratryl alcohol via veratrylglycerol. Veratryl alcohol is only slowly metabolized by the fungus, and accumulates.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-1106
    Keywords: Oxytocin cells ; Osmotic stimuli ; Milk ejection ; Paraventricular nucleus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Extracellular recordings were made from antidromically identified neurosecretory cells in the paraventricular nucleus of the hypothalamus in urethane-anesthetized lactating rats. Sixty-six percent of the rats tested (n=80) showed reflex milk ejections during suckling. Oxytocin neurones could be distinguished from other neurosecretory neurones by a characteristic high-frequency burst of spikes displayed before a reflex milk ejection. Twenty-three of the oxytocin neurones recorded from twenty-three individual animals were tested for the effect of intraperitoneal injection of 1.5 M NaCl (1 ml), which raised the plasma osmotic pressure from 299.3±2.4 (SE) mosmole/kg to 313.0±2.4 mosmole/kg. The injection significantly increased not only the firing rate of the oxytocin neurones (from 1.7±0.3 spikes/s to 4.9±0.6 spikes/s) but also the number of spikes per burst (from 53.6±7.4 to 75.5±7.5) and burst duration (from 3.38±0.22 s to 3.80±0.18 s). The amplitude of reflex milk ejection was also increased to 1.9 times. However, the injection did not change the interval between bursts. On the other hand, intraperitoneal injection of 0.15 M NaCl affected neither these parameters of oxytocin neurones nor the amplitude of milk ejection. Some of the antidromically identified neurones recorded in the rats which showed no detectable reflex milk ejection during suckling displayed intermitent bursts of action potentials. Ten of these neurones in ten individual rats were tested for the effect of 1.5 M NaCl. The number of spikes per burst was significiantly increased and reflex milk ejection was induced by the injection in eight of these rats. Then the bursts became milk ejection-related. These results indicate that increased plasma osmotic pressure influences the milk ejection reflex by enhancing the burst activity of oxytocin neurones which precedes reflex milk ejection.
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  • 6
    ISSN: 1432-1106
    Keywords: AV3V ; Paraventricular nucleus ; Oxytocinergic cell ; Vasopressinergic cell ; Osmoreceptor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To obtain electrophysiological evidence of an involvement of the anteroventral 3rd ventricle (AV3V) area in the osmotic control of neurohypophysial hormone release, extracellular action potentials of paraventricular (PVN) oxytocinergic and vasopressinergic cells during osmotic stimulation induced by i.p. injection of 1.5 M-NaCl solution were obtained from urethane anesthetized AV3V-lesioned, intact and sham-lesioned lactating rats. In intact and sham-lesioned rats the electrical activities of both oxytocinergic and vasopressinergic cells increased in response to the i.p. injection of hypertonic saline. After electrolytic lesion of the AV3V, the responsiveness of both types of cells to osmotic stimuli was severely impaired, whereas oxytocinergic cells were still capable of responding to suckling stimuli by displaying high frequency discharges of action potentials preceding milk-ejection. These results provide electrophysiological evidence that destruction of the AV3V area selectively impairs osmoregulatory input to PVN neurones and that the area has osmosensitive elements which activate the PVN neurosecretory cells when plasma osmotic pressure rises.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-1106
    Keywords: Area postrema ; Lesion ; Supraoptic nucleus ; Oxytocin ; Osmotic stimulation ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Experiments were performed to examine whether or not the area postrema (AP) is involved in the osmotic control of neurohypophysial hormone release. In control rats and in rats bearing extensive lesions of AP, extracellular action potentials were recorded from neurosecretory cells in the supraoptic nucleus (SON) and firing rates determined before and after the intraperitoneal (i.p.) injection of 1.5 M-NaCl solution. Lesion of the AP significantly (p≦0.05, Mann-Whitney's U-test) lowered firing rate of putative vasopressin (phasic) cells but not that of oxytocin (non-phasic) cells. In lesioned animals, i.p. injection of hypertonic saline, however, caused similar changes in plasma osmotic pressure, plasma oxytocin concentration and mean firing rates of both putative oxytocin and vasopressin cells to those in control rats. The results suggest that the osmotic control of SON neurosecretory cell activity in the rat can take place in the absence of the AP.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-1041
    Keywords: Phenytoin ; Gingival hyperplasia ; p-HPPH enantiomers ; CYP2C ; fibroblast culture ; adverse effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The purpose of this study was to assess the possible role of the (R)- and (S)- enantiomers of the phenytoin metabolite p-HPPH in the pathogenesis of gingival hyperplasia (GH). About 98% of circulating p-HPPH is in the (S)-form. There were significant differences between patients with and without GH in (R)-p-HPPH level (0.055 vs 0.042 μg·ml−1), both enantiomer/racemate level ratios, and R/S enantiomeric ratio (0.0313 vs 0.0232); an increase in serum (R)-p-HPPH level was observed in patients with GH. In separate experiments, the effect of p-HPPH enantiomers on the proliferation of the normal human dermal fibroblast was studied. The in vitro study showed that (R)-p-HPPH selectively stimulated fibroblast growth. The results suggest that the least abundant metabolite, (R)-p-HPPH, is the most toxic with respect to gingival hyperplasia.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-1041
    Keywords: Key words Phenobarbitone ; CYP2C19 ; Genetic polymorphism ; Pharmacokinetics ; NONMEM
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: The aim of this study was to clarify the effect of genetic polymorphisms of CYP2C19 on the pharmacokinetics of phenobarbitone (PB) using a nonlinear mixed-effects model (NONMEM) analysis in Japanese adults with epilepsy. Methods: A total of 144 serum PB concentrations were obtained from 74 subjects treated with both PB and phenytoin but without valproic acid. All patients were classified into three groups by CYP2C19 genotyping: G1, G2 and G3 were homozygous for the wild type of CYP2C19 (*1/*1), heterozygous extensive metabolizers (EMs), (*1/*2 or *1/*3), and poor metabolizers (PMs), (*2/*2, *2/*3), respectively. All data were analyzed using NONMEM to estimate pharmacokinetic parameters of PB with respect to the CYP2C19 genotype. Results: Thirty-three patients belonged to G1 (44.6%), 35 to G2 (47.3%), and 6 to G3 (8.1%). The total clearance (CL) of PB significantly decreased by 18.8% in PMs (G3) relative to EMs (G1 and G2). The CL tended to be lower in G2 than in G1. Conclusion: In this study, we first demonstrated the effect of the CYP2C19 polymorphism on pharmacokinetics of PB by genotyping. The contribution of other metabolic enzymes in the metabolism of PB in humans remains to be elucidated; however, it appears that the disposition of PB is mediated in part by this enzyme. The estimated population clearance values in the three genotype groups can be used to predict the PB dose required to achieve an appropriate serum concentration in an individual patient.
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  • 10
    ISSN: 1432-1041
    Keywords: Key words Tamsulosin ; Protein binding ; Renal disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract   Objective: To investigate the factors that affect the plasma protein binding of tamsulosin in patients with lowered renal function compared with that in healthy subjects and to evaluate the possibility of binding interactions. Methods: Blood was donated from patients with renal dysfunction and from healthy subjects. The binding of 14C-tamsulosin to plasma proteins was determined by the ultrafiltration method. In addition, plasma protein binding interactions were investigated between tamsulosin and other drugs used concomitantly. Results: The mean percentage of unbound 14C-tamsulosin was 0.90% in the healthy subjects (control) and was 0.71% in the patients. The unbound fraction in the patients with α1-acid glycoprotein (α1-AGP) levels over 0.9 mg/ml was significantly lower than that in the healthy subjects. In contrast, the unbound fraction in the patients with α1-AGP levels less than 0.7 mg/ml, which is the mean normal level, was almost equal to the control levels. A significant correlation existed between the Cb/Cu of tamsulosin and plasma α1-AGP level (r 2 = 0.580, P 〈 0.001), while no correlation existed between the Cb/Cu and plasma albumin level (r 2 = 0.021, P = 0.381) in both groups. No apparent binding interactions were observed between tamsulosin and the other drugs examined. Conclusions: Tamsulosin is highly bound to α1-AGP. The extent of plasma protein binding of tamsulosin correlated with the α1-AGP level but not with the albumin level. Furthermore, there appears to be no or little possibility of binding interactions between tamsulosin and other drugs in clinically concomitant use, despite its strong binding to α1-AGP.
    Type of Medium: Electronic Resource
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