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  • 1
    Electronic Resource
    Electronic Resource
    CP-123,369: A potent, orally active immunosuppressive agent (1995)
    Springer
    Inflammation research 44 (1995), S. S183 
    Details
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01778322
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  • 2
    Electronic Resource
    Electronic Resource
    Ion channel modulation as a drug discovery target in inflammatory diseases (1996)
    Springer
    Inflammation research 45 (1996), S. 435-437 
    Details
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02252312
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  • 3
    Electronic Resource
    Electronic Resource
    Haemolysis due to formaldehyde-induced anti-N-like antibodies in haemodialysis patients (1979)
    Springer
    Journal of molecular medicine 57 (1979), S. 673-679 
    Details
    ISSN: 1432-1440
    Keywords: Formaldehyd ; Anti-N-artige Antikörper ; Immunhämolyse ; Hämodialyse ; renale Anämie ; Formaldehyde ; Anti-N-like antibodies ; Immunohaemolysis ; Haemodialysis ; Renal anaemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary During reuse of formaldehyde sterilized Kiil-dialysers, red cell survival, measured by means of51Cr t/2, was significantly reduced (p〈0.001) in 16 patients with anti-N-like positive sera, when compared with 19 antibody negative control patients (Mean±SD: 16.5±2.7 versus 22.4±3.1 days.) In antibody negative patients (n=10) replacement of form-aldehyde sterilized dialysers by ethylene-oxide sterilized disposable dialysers resulted in a significant increase (p〈0.002) of51Cr t/2 (Mean±SD, days: Kiil-dialyser 16.3±1.9; disposable dialyser 20.3±3.5). This improvement took place, although antibody titres persisted during the51Cr-measurements and declined thereafter only slowly. In antibody negative patients (n=6) red cell survival did not increase, when formaldehyde as a sterilant was avoided. In antibody positive patients mean haematocrit rose significantly (p〈0.05), whereas in none of the antibody negative patients a definite change of haematocrit occurred. The data demonstrate, that formaldehyde sterilisation of dialysers may cause antibody-mediated haemolysis contributing to the extent of renal anaemia. This immunohaemolysis may be corrected, in spite of continuing antibody persistance, when formaldehyde exposure is totally avoided, or possibly when minimized.
    Notes: Zusammenfassung Während der Wiederverwendung Formaldehyd-sterilisierter Kiil-Dialysatoren war die mit51Cr bestimmte Erythrocytenüberlebenszeit bei 16 Patienten mit Anti-N-artigen Antikörpern significant (p〈0,001) kürzer als bei 19 Antikörper-negativen Kontrollpatienten (MW±SD: 16,5±2,7 bzw. 22,4±3,1 Tage). Bei Antikörper-positiven Patienten (n=10) führte das Umsetzen von Formaldehyd-sterilisierten Kiil-Dialysatoren auf Ethylenoxid-sterilisierte Einmaldialysatoren vergleichbarer Effektivität zu einem sofortigen, signifikanten (p〈0,002) Anstieg der Erythrocytenüberlebenszeit (MW±SD: 16,3±1,9 Tage, Kiil-Dialysator; 20,3±3,5 Tage Einmaldialysator). Die Antikörper-Titer blieben während der Messung der Erythrocytenüberlebenszeit unverändert, danach fielen sie im Verlauf von Monaten langsam ab. Bei Antikörper-negativen Kontrollpatienten (n=6) führte das Umsetzen von Formaldehyd-sterilisierten Kiil-Dialysatoren auf die Ethylenoxid-sterilisierten Einmaldialysatoren nicht zum Anstieg der Erythrocytenüberlebenszeit. Bei den Antikörper-positiven Patienten stieg der mittlere Hämatokritwert nach dem Umsetzen signifikant (p〈0,05) an, dagegen kam es nach dem Umsetzen bei keinem der Antikörper-negativen Patienten zu einer gerichteten Veränderung der Hämatokritwerte. Die Untersuchungen belegen, daß die Formaldehyd-Sterilisation von Dialysatoren zu einer Antikörper-vermittelten Hämolyse führen kann, die zum Ausmaß der renalen Anämie dieser Patienten beiträgt. Diese Immunhämolyse kann, auch bei Persistenz der Anti-N-artigen Antikörper, zumindest teilweise verhindert werden, wenn eine weitere Formaldehyd-Exposition des Patienten vermieden wird.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01477668
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  • 4
    Electronic Resource
    Electronic Resource
    Die Rolle des Erythropoietinmangels in der Pathogenese der renalen Anämie (1979)
    Springer
    Journal of molecular medicine 57 (1979), S. 1031-1036 
    Details
    ISSN: 1432-1440
    Keywords: Renal anemia ; Pathogenesis ; Erythropoietin deficiency ; Renale Anämie ; Pathogenese ; Erythropoietinmangel
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Es wird eine Übersicht gegeben über klinische Untersuchungen, die mit einem hochsensiblen in-vitro Erythropoietin Assay (foetale Mäuseleberzellkultur) zur Klärung der umstrittenen Rolle des Erythropoietinmangels in der Pathogenese der renalen Anämie an großen Patientenpopulationen durchgeführt wurden. Die Studien betrafen: a.) chronisch Nierenkranke mit variierender Funktionsein-schränkung in der Vordialysephase b.) nicht nephrektomierte und anephrische chronische Dialysepatienten. Die bisher vorliegenden Ergebnisse belegen, daß die Anfangsphase der renalen Anämie mit einem kompensatorischen Anstieg der Serumerythropoietinkonzentration einhergeht und somit ein Erythropoietinmangel nicht die primäre Ursache dieser Anämie sein kann; lediglich ein relativer Erythropoietinmangel ist anzunehmen. Erst in der Terminalphase der Niereninsuffizienz wird der Erythropoietinmangel absolut, so bei 50% der untersuchten chronischen, nichtnephrektomierten Hämodialysepatienten und bei allen anephrischen Patienten. An einzelnen Patienten läßt sich aber selbst in der terminalen Niereninsuffizienz eine Regulierbarkeit der Serumerythropoietinkonzentration über den Hämatokrit im Sinne eines negativen feedback nachweisen, der auf einem subnormalen Hämatokritniveau arbeitet.
    Notes: Summary A review is given of clinical studies performed by use of a highly sensitive in-vitro erythropoietin assay (fetal mouse livercell culture) in large patients' populations to clarify the controversial role of erythropoietin deficiency in the pathogenesis of renal anemia. Studies involved a.) patients with chronic renal disease and varying degree of renal insufficiency in the predialysis phase b.) non-nephrectomized and anephric patients on regular hemodialysis treatment. The data available demonstrate that the initial phase of renal anemia is accompanied by a compensatory increase of serumerythropoietin concentration and therefore erythropoietin deficiency has to be excluded as a primary cause of the anemia of renal failure; merely a relative lack of erythropoietin seems to exist. In the terminal phase of renal failure, erythropoietin deficiency becomes absolute, such in 50% of the investigated non-nephrectomized hemodialysis patients and in all anephric patients. However in individual patients even in terminal renal failure a sustained regulatory feedback mechanism between serume-rythropoietin concentration and hematocrit, probably working at lower hematocrit level, could be demonstrated.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01479988
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  • 5
    Electronic Resource
    Electronic Resource
    Kinetics of canrenone after single and multiple doses of spironolactone (1979)
    Springer
    European journal of clinical pharmacology 16 (1979), S. 255-262 
    Details
    ISSN: 1432-1041
    Keywords: spironolactone ; canrenone ; fluorimetry ; high performance liquid chromatography ; linear kinetics ; saturation kinetics ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In Study I 20 normal volunteers received a single oral dose of spironolactone 100 mg. In Study II a further 20 normal volunteers were given first spironolactone 100 mg b.i.d. and subsequently spironolactone 100 mg once a day for a further 4 days. In Study III 5 normal subjects were given a single dose of spironolactone 500 mg. The concentration of canrenone in serum was determined both by fluorimetry and HPLC for 0–48 h in Study I, 120–168 h in Study II and 0–36 h in Study III. The total AUCs after the single 100 mg dose did not differ from the AUCs within the dosing interval during steady state. The half-lives of the terminal log-linear phases were almost identical (14.99±0.80 h and 15.69±0,80 h) when determined by fluorimetry, and were sligthly, but significantly (p〈0.01), longer when determined by HPLC — 20.14±1.62 and 18.71±1.04. The mean ratio of the specific AUC determined by HPLC and the fluorimetrically determined AUC was 0.3 after the single 100 mg dose. It did not differ from the corresponding value during steady state (0.34). In contrast, the ratio after the single 500 mg dose was approximately 50% higher. Fluorimetrically determined AUCs after 100 and 500 mg doses did not show dose-proportionality in contrast to the HPLC-determined AUCs. It was concluded that Canrenone contributes much less to the conventional fluorimetric determination than was previously assumed. It may not provide more than 1/10 and 1/4 of the antimineralocorticoid activity of spironolactone after single dose and multiple doses, respectively. Whereas linear kinetics apply after single and multiple 100 mg doses of spironolactone, after 500 mg saturation kinetics must be assumed with respect to metabolism. Thus, in bioavailability studies high doses of spironolactone should be avoided. For such studies the fluorimetric assay seems to be the appropriate bioanalytical method in spite of its lower specificity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00608404
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  • 6
    Electronic Resource
    Electronic Resource
    Disposition pharmacokinetics of bezafibrate in man (1979)
    Springer
    European journal of clinical pharmacology 16 (1979), S. 31-38 
    Details
    ISSN: 1432-1041
    Keywords: bezafibrate ; hyperlipoproteinemia ; bioavailability ; pharmacokinetics ; GC-MS
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The disposition kinetics of bezafibrate, a newly developed drug of great lipid-lowering potency, were investigated in normal male subjects. Five male volunteers received14C-labelled bezafibrate orally in solution, and a further 10 were given the same dose (300 mg) of un-labelled drug as tablets. The concentration of bezafibrate in serum and urine from the latter was determined by GC, and in the former total radioactivity in serum, urine and feces was followed for 48 h, and urinary excretion products were analysed by TLC and GC-MS. Rapid absorption from the gastrointestinal tract led to peak serum levels 30 min and 2 h after administration of solution and tablets, respectively. Since approximately 95% of the administered14C-bezafibrate was excreted in urine within 48 h, and almost all the remainder was detected in feces, absorption can be regarded as complete after administration in solution. The relative optimal bioavailability from the tablets was also complete, since in both cases approximately 50% of the administered dose was detected as unchanged bezafibrate in urine within 24 h by GC in the tablet study, and by TLC in the solution study. Of the decomposition products, more than 20% of the dose was present as glucuronides and the remainder consisted of several more polar compounds, one of which was identified as a hydroxyderivative of bezafibrate. Since the apparent halflife of bezafibrate in serum was 2.1 h, this new drug possesses favourable pharmacokinetic features: rapid and complete absorption, even from tablets, combined with a conveniently short half-life, and clearance which is half renal (56 ml/min) and half metabolic (43 ml/min), giving a total clearance of 99 ml/min.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00644963
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  • 7
    Electronic Resource
    Electronic Resource
    Structures of some of the minor aminoglycoside factors of the nebramycin fermentation (1978)
    s.l. : American Chemical Society
    The @journal of organic chemistry 43 (1978), S. 1430-1434 
    Details
    ISSN: 1520-6904
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1021/jo00401a030
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  • 8
    Electronic Resource
    Electronic Resource
    The safety of ranitidine in over a decade of use (1997)
    Oxford BSL : Blackwell Science
    Alimentary pharmacology & therapeutics 11 (1997), S. 0 
    Details
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background: Ranitidine hydrochloride (Zantac) is one of the most extensively studied and widely used drugs of all time. This has provided an excellent opportunity to define its safety profile. Methods: Data from 189 controlled clinical trials in which more than 26000 patients received daily doses of ranitidine for 4 weeks or more were reviewed. More than 80% of patients were treated with up to 300 mg ranitidine daily; the remaining patients received doses of up to 1200 mg daily. Eighty-seven trials were placebo controlled. Analyses of post-marketing surveillance and a database of all spontaneously reported adverse events were also evaluated. Results: Overall in the clinical trial programme adverse events were reported by 20% of those receiving ranitidine compared with 27% of those receiving placebo. The pattern of events was similar in all treatment groups with no evidence of dose-related toxicity in regimens encompassing an eightfold range of therapeutic doses. Similarly in a programme of studies designed to evaluate a dose of ranitidine of 75  mg for non-prescription (over-the-counter) use in the treatment of heartburn, ranitidine was not associated with an adverse event profile distinct from that of placebo. Analysis of spontaneously reported adverse event data allowed identification of rare idiosyncratic events. Conclusions: Review of data from a large population of controlled clinical trials with analyses of postmarketing surveillance studies and spontaneously reported adverse events confirmed the excellent safety profile of ranitidine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2036.1997.136312000.x
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  • 9
    Electronic Resource
    Electronic Resource
    CARBOHYDRATE-MODULATED GENE EXPRESSION IN PLANTS (1996)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Plant Physiology and Plant Molecular Biology 47 (1996), S. 509-540 
    Details
    ISSN: 1040-2519
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract Plant gene responses to changing carbohydrate status can vary markedly. Some genes are induced, some are repressed, and others are minimally affected. As in microorganisms, sugar-sensitive plant genes are part of an ancient system of cellular adjustment to critical nutrient availability. However, in multicellular plants, sugar-regulated expression also provides a mechanism for control of resource distribution among tissues and organs. Carbohydrate depletion upregulates genes for photosynthesis, remobilization, and export, while decreasing mRNAs for storage and utilization. Abundant sugar levels exert opposite effects through a combination of gene repression and induction. Long-term changes in metabolic activity, resource partitioning, and plant form result. Sensitivity of carbohydrate-responsive gene expression to environmental and developmental signals further enhances its potential to aid acclimation. The review addresses the above from molecular to whole-plant levels and considers emerging models for sensing and transducing carbohydrate signals to responsive genes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.arplant.47.1.509
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  • 10
    Electronic Resource
    Electronic Resource
    Effect of Salinity and Potassium on the Uptake of Nitrogen and on Nitrogen Metabolism in Young Barley Plants (1975)
    Oxford, UK : Blackwell Publishing Ltd
    Physiologia plantarum 35 (1975), S. 0 
    Details
    ISSN: 1399-3054
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology
    Notes: In a solution culture experiment with 4-week-old barley plants (variety Villa) the influence of NaCl salinization and of KCl additions on the uptake and turnover of labelled N (15NH415NO3) was studied. Labelled N was applied for 24 h at the end of the growth period.Salinization impaired growth and uptake of labelled N. The incorporation of labelled N into the protein fraction, however, was improved by NaCl salinization. Additions of KCl to the nutrient solution diminished the negative effect of NaCl salinization on growth. At both NaCl salinization levels (60 and 120 mM) K additions favoured the uptake of labelled N and particularly its incorporation into the protein fraction.It is suggested that the negative influence of the NaCl stress is not primarily due to an impaired protein synthesis, but is possibly caused by a deterimental effect of Na on other metabolic processes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1399-3054.1975.tb03911.x
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