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  • 1
    Electronic Resource
    Electronic Resource
    Alpha-1-Mikroglobulin in Urin und Serum bei Proteinurie und Niereninsuffizienz (1985)
    Springer
    Journal of molecular medicine 63 (1985), S. 711-717 
    Details
    ISSN: 1432-1440
    Keywords: Alpha-1-microglobulin ; Beta-2-microglobulin ; Proteinuria ; Renal insufficiency
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Alpha-1-microglobulin (alpha-1-m) is a low molecular weight glycoprotein (mw 25–33 KD) that is filtered through the glomeruli and reabsorbed in the proximal parts of the renal tubules where it is catabolized. Normal ranges were established for alpha-1-m (100 healthy controls) in serum (20–42 mg/l) and urine (3.5–8 mg/l). Alpha-1-m was then measured in 341 urine samples whose protein pattern had been classified as “pathologic” and “normal” according to microelectrophoresis. Increased alpha-1-m concentrations were found in 266 out of 280 pathologic urines (5% false negative) and in 3 out of 61 normal urines (4% false positive). Beta-2-microglobulin (beta-2-m), total protein or protein test strips showed a poorer correlation to the electrophoretic results. Measurement of alpha-1-m is, therefore, the most sensitive of these methods for the detection of proteinuria. In 90 patients with low molecular weight proteinuria and either with or without renal insufficiency alpha-1-m concentrations were determined in both urine and serum. While all patients had elevated urinary alpha-1-m concentrations, increased serum values were only found in renal insufficiency (Ccrea〈100 ml/min). Independently of these results, we were also able to establish that increased alpha-1-m levels are found at decreased glomerular filtration rates (Ccrea 〈70 ml/min). Pathologic alpha-1-m concentrations therefore only allow the conclusion of isolated tubular impairment when the GFR is greater than 70 ml/min. Data from 350 patients with various renal and hypertensive diseases showed that serum alpha-1-m is a more sensitive indicator of renal insufficiency, even in the so-called “creatinine blind” range (60–100 ml/min) of the GFR than either creatinine or beta-2-m.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01733115
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Plasma-Endothelin bei Normalpersonen und Patienten mit nephrologisch-rheumatologischen und kardiovaskulären Erkrankungen (1990)
    Springer
    Journal of molecular medicine 68 (1990), S. 774-779 
    Details
    ISSN: 1432-1440
    Keywords: Endothelin ; Hypertension ; Coronary artery disease ; Renal insufficiency ; Rheumatoid arthritis ; Lupus erythematodes ; Liver cirrhosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Plasma concentrations of the recently isolated potent vasoconstrictory peptide endothelin were measured in 382 patients. The investigations were performed by means of a sensitive radioimmunoassay specific for Endothelin-1, 2. The results from 110 healthy volunteers displayed a normal range of 44.67±3.51 pg/ml. Significantly raised levels were found in 33 patients with chronic end-stage renal failure both before and after hemodialysis. In contrast, 35 patients with compensated renal insufficiency did not differ from the normals. Sixty-five patients after kidney transplantation revealed significantly elevated levels, as did 27 patients with acute myocardial infarction, 8 after coronary bypass surgery, and 5 with liver cirrhosis. The mean values of 27 patients with untreated hypertension, 22 with secondary hypertension, of various causes and 16 with coronary artery disease were comparable to the normal population. The values were significantly decreased in 9 pregnant women with hypertension and proteinuria. A marked decline was found in 5 patients with systemic lupus erythematodes, while 20 patients with rheumatoid arthritis demonstrated only a slight decrease. The pathophysiological role of endothelin as a local or circulating hormone in regulating systemic blood pressure or release of other hormones remains to be determined.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01647248
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  • 3
    Electronic Resource
    Electronic Resource
    Inhibition of human adrenal androgen secretion by ketoconazole (1989)
    Springer
    Journal of molecular medicine 67 (1989), S. 707-712 
    Details
    ISSN: 1432-1440
    Keywords: Ketoconazole ; Androgens ; Inhibition of adrenal androgen secretion ; Hirsutism ; Hyperandrogenism therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of ketoconazole on adrenal androgen secretion was examined in 15 patients with elevated serum androgens. In a dose of 600 mg per day orally ketoconazole inhibited the biosynthesis of all measured androgens. The mean reduction in serum levels of dehydroepiandrosterone sulfate was 32%, of dehydroepiandrosterone 54%, of androstenedione 52%, and of testosterone 43%; mean serum levels of cortisol only fell by 19%. The reduction in serum androgen levels was first significant 24 h after beginning of treatment and persisted as long as the drug was administered. We conclude that ketoconazole inhibits adrenal androgen biosynthesis more pronouncedly than cortisol biosynthesis. This might be of clinical benefit in the treatment of hirsutism and other states of androgen hypersecretion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01721288
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    Paper (German National Licenses)
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  • 4
    Electronic Resource
    Electronic Resource
    Different inhibitory effect of etomidate and ketoconazole on the human adrenal steroid biosynthesis (1993)
    Springer
    Journal of molecular medicine 71 (1993), S. 933-938 
    Details
    ISSN: 1432-1440
    Keywords: Etomidate ; Ketoconazole ; Steroid biosynthesis ; Adrenal gland ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The narcotic agent etomidate and the antimycotic drug ketoconazole are known to block steroid biosynthesis in man. To study the different effects of these imidazole derivatives on human adrenal steroid biosynthesis we incubated slices of human adrenal glands with 3H-labeled precursors and increasing concentrations of etomidate or ketoconazole (0-2000 μM). After extraction the labeled metabolites were separated by thin-layer chromatography and quantified by scintillation counting. Etomidate inhibited most potently 11β-hydroxylase activity by suppressing the formation of corticosterone from 11-deoxycorticosterone to 1 % of control [50% inhibitory concentration (IC50) 0.03 μM] while ketoconazole suppressed 11β-hy-droxylase to only 39% of control activity (IC50 15 μM). Ketoconazole however, most potently blocked the conversion of 17α-hydroxy-proges-terone to androstenedione by C17,20-desmolase to about 15% of control activity (IC50 1 μM) while etomidate showed a much weaker effect on this enzyme with a suppression to 50% of C17,20-desmolase control activity at a concentration of 380 μM. Both imidazole drugs showed a similar strong inhibitory effect on the activity of 17α-hy-droxylase (IC50 6-18 μM) and 16α-hydroxylase (IC50 4–8 μM) and did not affect 21-hydroxylase. These in vitro data indicate a predominant inhibitory effect of etomidate on corticosteroid biosynthesis by relative selective inhibition of 11β-hydroxylase and of ketoconazole on the adrenal androgen biosynthesis by a predominant inhibition of C17,20-desmolase. This differential inhibitory effect of etomidate and ketoconazole on human steroid biosynthesis may be of clinical importance for a possible therapeutic use of these imidazole derivatives in endocrine disorders.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00185607
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    Paper (German National Licenses)
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