Zerstörungsfreie Charakterisierung mechanischer Eigenschaften von hartstoffpartikelhaltigen Passivierungsschichten auf galvanischen Zink- und Zinklegierungsschichten

Zur Verbesserung des Korrosionsschutzes spielen Passivierungsschichten auf galvanischen Zn- und ZnNi-Schichten eine wesentliche Rolle. Im Bereich der Automobilindustrie sowie der Elektrotechnik/Elektronik wurde durch entsprechende Richtlinien (EU-Altfahrzeugrichtlinie usw.), welche in deutsches Recht umgesetzt wurden, der Einsatz von hexavalentem Chrom in allen Fahrzeugbauteilen sowie vielen Elektro- und Elektronikgeräten verboten. Somit ist die Anwendung der durch sehr gute Korrosionsschutzeigenschaften gekennzeichneten Chrom(VI)-haltigen Gelb-, Schwarz-und Olivchromatierungen für Zink- und Zinklegierungsschichten verboten bzw. stark eingeschränkt. Auf Grund des Cr(VI)-Verbotes werden heute vor allem Dickschichtpassivierungen eingesetzt. Ohne den für Cr(VI)-haltige Schichten typischen Selbstheilungseffekt sind dieses Schichten wegen ihrer geringen Härte anfällig für mechanische Verletzungen, so dass speziell bei Trommelware die geforderten Korrosionsschutzeigenschaften nur durch zusätzliche silikatische oder organische Topcoats erreicht werden können. Durch die Einlagerung von nanokristallinen Hartstoffpartikeln in die Passivierungsschicht kann die Verschleißbeständigkeit und hierüber durch die Vermeidung von Oberflächenverletzungen während der Herstellung sowie des Bauteiltransports auch die Korrosionsbeständigkeit erhöht werden. Für die Entwicklung und den praktischen Einsatz dieser Schichten ist die Materialcharakterisierung, insbesondere die Charakterisierung der mechanischen Eigenschaften, von herausragender Bedeutung. Im vorliegenden Beitrag soll die zerstörungsfreie bzw. zerstörungsarme, tiefenabhängige Bestimmung der mechanischen Schichteigenschaften unter Nutzung der instrumentierten Eindringhärteprüfung (Nanoindenter) vorgestellt werden. Der Einfluss der verschiedenen Hartstoffpartikel (Aluminiumoxid, Siliciumoxid usw.) auf die Schichteigenschaften wird ausführlich diskutiert

Caloric restriction counteracts age-dependent changes in prolyl-4-hydroxylase domain (PHD) 3 expression

Caloric restriction remains the most reproducible measure known to extend life span or diminish age-associated changes. Previously, we have described an elevated expression of the prolyl-4-hydroxylase domain (PHD) 3 with increasing age in mouse and human heart. PHDs modulate the cellular response towards hypoxia by regulating the stability of the α-subunit of the transcriptional activator hypoxia inducible factor (HIF). In the present study we demonstrate that elevated PHD3, but not PHD1 or PHD2, expression is not restricted to the heart but does also occur in rat skeletal muscle and liver. Elevated expression of PHD3 is counteracted by a decrease in caloric intake (40% caloric restriction applied for 6 months) in all three tissues. Age-associated changes in PHD3 expression inversely correlated with the expression of the HIF-target gene macrophage migration inhibitory factor (MIF), which has been previously described to be involved in cellular HIF-mediated anti-ageing effects. These data give insight into the molecular consequences of caloric restriction, which influences hypoxia-mediated gene expression via PHD3

Role of the Fusarium fujikuroi TOR Kinase in Nitrogen Regulation and Secondary Metabolism

In Fusarium fujikuroi, the biosynthesis of gibberellins (GAs) and bikaverin is under control of AreA-mediated nitrogen metabolite repression. Thus far, the signaling components acting upstream of AreA and regulating its nuclear translocation are unknown. In Saccharomyces cerevisiae, the target of rapamycin (TOR) proteins, Tor1p and Tor2p, are key players of nutrient-mediated signal transduction to control cell growth. In filamentous fungi, probably only one TOR kinase-encoding gene exists. However, nothing is known about its function. Therefore, we investigated the role of TOR in the GA-producing fungus F. fujikuroi in order to determine whether TOR plays a role in nitrogen regulation, especially in the regulation of GA and bikaverin biosynthesis. We cloned and characterized the F. fujikuroi tor gene. However, we were not able to create knockout mutants, suggesting that TOR is essential for viability. Inhibition of TOR by rapamycin affected the expression of AreA-controlled secondary metabolite genes for GA and bikaverin biosynthesis, as well as genes involved in transcriptional and translational regulation, ribosome biogenesis, and autophagy. Deletion of fpr1 encoding the FKBP12-homologue confirmed that the effects of rapamycin are due to the specific inhibition of TOR. Interestingly, the expression of most of the TOR target genes has been previously shown to be also affected in the glutamine synthetase mutant, although in the opposite way. We demonstrate here for the first time in a filamentous fungus that the TOR kinase is involved in nitrogen regulation of secondary metabolism and that rapamycin affects also the expression of genes involved in translation control, ribosome biogenesis, carbon metabolism, and autophagy

Impact of Ammonium Permeases MepA, MepB, and MepC on Nitrogen-Regulated Secondary Metabolism in Fusarium fujikuroi▿

In Fusarium fujikuroi, the production of gibberellins and bikaverin is repressed by nitrogen sources such as glutamine or ammonium. Sensing and uptake of ammonium by specific permeases play key roles in nitrogen metabolism. Here, we describe the cloning of three ammonium permease genes, mepA, mepB, and mepC, and their participation in ammonium uptake and signal transduction in F. fujikuroi. The expression of all three genes is strictly regulated by the nitrogen regulator AreA. Severe growth defects of ΔmepB mutants on low-ammonium medium and methylamine uptake studies suggest that MepB functions as the main ammonium permease in F. fujikuroi. In ΔmepB mutants, nitrogen-regulated genes such as the gibberellin and bikaverin biosynthetic genes are derepressed in spite of high extracellular ammonium concentrations. mepA mepB and mepC mepB double mutants show a similar phenotype as ΔmepB mutants. All three F. fujikuroi mep genes fully complemented the Saccharomyces cerevisiae mep1 mep2 mep3 triple mutant to restore growth on low-ammonium medium, whereas only MepA and MepC restored pseudohyphal growth in the mep2/mep2 mutant. Overexpression of mepC in the ΔmepB mutants partially suppressed the growth defect but did not prevent derepression of AreA-regulated genes. These studies provide evidence that MepB functions as a regulatory element in a nitrogen sensing system in F. fujikuroi yet does not provide the sensor activity of Mep2 in yeast, indicating differences in the mechanisms by which nitrogen is sensed in S. cerevisiae and F. fujikuroi

Isotretinoin Use and Compliance with the Dutch Pregnancy Prevention Programme A Retrospective Cohort Study in Females of Reproductive Age Using Pharmacy Dispensing Data

Background: Isotretinoin is very effective in the treatment of severe acne. However, because of the teratogenic properties of this agent an isotretinoin Pregnancy Prevention Programme (PPP) was implemented in the Netherlands to guarantee that treatment is contraindicated in women of reproductive age unless at least one effective method of contraception is used. Furthermore, the PPP stipulates that isotretinoin treatment should be managed by physicians or specialists experienced in treatment with this drug and that only monthly prescriptions are issued. Objective: To assess compliance with the Dutch isotretinoin PPP in women of reproductive age during the study period of 1 January 2005 to 31 December 2008. Methods: Detailed information on dispensed medication and co-medication was available from the Dutch Foundation of Pharmaceutical Statistics. Four types of outcome were studied: concomitant dispensing of hormonal contraceptive with isotretinoin; the proportion of specialist prescribing of isotretinoin; prescribing of conventional acne therapy prior to isotretinoin initiation; and isotretinoin dispensing exceeding the maximum amount. The use of contraceptives in women aged between 15 and 45 years was defined as concomitant if the period of systemic contraceptive use overlapped the period of isotretinoin dispensing for at least 10 days, or if any dispensing of an intrauterine or intravaginal contraceptive was recorded since the year 2000. Dispensings were separated into those prescribed by either specialists or general practitioners (GPs). The use of antibacterials, anti-androgens or topical agents against acne was checked 4 months prior to an isotretinoin dispensing, and a possible excess of the maximum amount of isotretinoin was defined as prescriptions of more than 100 defined daily doses. Results: During the study period, data were available for 442 Dutch pharmacies encompassing 4881 women of reproductive age using isotretinoin at least once during study period. Among women of reproductive age, the use of isotretinoin increased during the study period. The proportion of isotretinoin initiation with concomitant oral hormonal or intrauterine contraceptives was low (59.3% [95% CI 57.6, 61.0]). Initiation of isotretinoin by a specialist increased the chance for concomitant contraception by 26% (95% CI 6.0, 49.0); in 78.2% (95% CI 76.8, 79.6) of women, isotretinoin was initiated by a specialist. Conventional acne therapy up to 16 months prior to isotretinoin initiation was found in 70% of the women (70.3% [95% CI 66.0, 74.6]). In 1.4% (95% CI 1.0, 1.8) of cases of treatment initiation, the amount of isotretinoin dispensed on one prescription seemed too high. Conclusion: Attention should be paid to improving the implementation of the isotretinoin PPP. Despite clear guidelines and warnings in the product information, our study strongly suggests that concomitant use of isotretinoin and contraceptives is too low. Even though we will have missed non-pharmacological forms of contraception, these results raise doubts about the safe use of isotretinoin in women of reproductive age in the Netherlands. Furthermore, isotretinoin does not seem to be used in cases of severe acne only. Reserving isotretinoin prescribing to specialists may improve adherence to the PPP

Isotretinoin use and compliance with the Dutch Pregnancy Prevention Programme: a retrospective cohort study in females of reproductive age using pharmacy dispensing data.

Item does not contain fulltextBACKGROUND: Isotretinoin is very effective in the treatment of severe acne. However, because of the teratogenic properties of this agent an isotretinoin Pregnancy Prevention Programme (PPP) was implemented in the Netherlands to guarantee that treatment is contraindicated in women of reproductive age unless at least one effective method of contraception is used. Furthermore, the PPP stipulates that isotretinoin treatment should be managed by physicians or specialists experienced in treatment with this drug and that only monthly prescriptions are issued. OBJECTIVE: To assess compliance with the Dutch isotretinoin PPP in women of reproductive age during the study period of 1 January 2005 to 31 December 2008. METHODS: Detailed information on dispensed medication and co-medication was available from the Dutch Foundation of Pharmaceutical Statistics. Four types of outcome were studied: concomitant dispensing of hormonal contraceptive with isotretinoin; the proportion of specialist prescribing of isotretinoin; prescribing of conventional acne therapy prior to isotretinoin initiation; and isotretinoin dispensing exceeding the maximum amount. The use of contraceptives in women aged between 15 and 45 years was defined as concomitant if the period of systemic contraceptive use overlapped the period of isotretinoin dispensing for at least 10 days, or if any dispensing of an intrauterine or intravaginal contraceptive was recorded since the year 2000. Dispensings were separated into those prescribed by either specialists or general practitioners (GPs). The use of antibacterials, antiandrogens or topical agents against acne was checked 4 months prior to an isotretinoin dispensing, and a possible excess of the maximum amount of isotretinoin was defined as prescriptions of more than 100 defined daily doses. RESULTS: During the study period, data were available for 442 Dutch pharmacies encompassing 4881 women of reproductive age using isotretinoin at least once during study period. Among women of reproductive age, the use of isotretinoin increased during the study period. The proportion of isotretinoin initiation with concomitant oral hormonal or intrauterine contraceptives was low (59.3% [95% CI 57.6, 61.0]). Initiation of isotretinoin by a specialist increased the chance for concomitant contraception by 26% (95% CI 6.0, 49.0); in 78.2% (95% CI 76.8, 79.6) of women, isotretinoin was initiated by a specialist. Conventional acne therapy up to 16 months prior to isotretinoin initiation was found in 70% of the women (70.3% [95% CI 66.0, 74.6]). In 1.4% (95% CI 1.0, 1.8) of cases of treatment initiation, the amount of isotretinoin dispensed on one prescription seemed too high. CONCLUSION: Attention should be paid to improving the implementation of the isotretinoin PPP. Despite clear guidelines and warnings in the product information, our study strongly suggests that concomitant use of isotretinoin and contraceptives is too low. Even though we will have missed non-pharmacological forms of contraception, these results raise doubts about the safe use of isotretinoin in women of reproductive age in the Netherlands. Furthermore, isotretinoin does not seem to be used in cases of severe acne only. Reserving isotretinoin prescribing to specialists may improve adherence to the PPP