In rat experiments and a clinical trial we have examined the suspected nephrotoxic potential of 5-aminosalicylic acid (5-ASA), the biological active metabolite of sulfasalazine (SZ). Male Wistar rats were treated orally for 4 weeks daily with 30 and 200 mg 5-ASA/kg and 75 and 500 mg SZ/kg. The two renal marker enzymes N-acetyl-beta-D-glucosaminidase (NAG; EC 3.2.1.30), alanineaminopeptidase (AAP; EC 3.4.11.2) and creatinine were monitored in urine. At the end of the experiment rats were sacrificed, the removed kidneys histologically examined and drugs, their metabolites and creatinine measured in plasma and urine. In 9 patients treated chronically for their Crohn's disease with 3 X 0.5 g 5-ASA daily in form of suppositories and an oral preparation urinary excretions of NAG, AAP and serum creatinine were also monitored before and during therapy. Neither the animal experiments nor the observations in patients gave any evidence of nephrotoxic lesions induced by 5-ASA. Thus, our data show that in the doses applied, 5-ASA was devoid of altering renal excretion in rats and man.
Circadian rhythms of catecholamines, cortisol and prolactin were investigated in 4 healthy subjects and in 6 patients suffering from an apallic syndrome. The clinical picture of this syndrome is characterized by disturbed consciousness (coma vigile), suspension of the sleeping and waking rhythm, lack of emotional reactions and appearance of primitive motor patterns. With the exception of dopamine a pronounced circadian rhythm was found in the control group for all investigated parameters. Catecholamines and cortisol showed a good correlation in the temporal pattern of plasma concentrations and urinary excreted amounts. In all apallic patients the circadian rhythm of prolactin was abolished. Only in one patient a rhythm of catecholamines and in 2 patients a rhythm of cortisol was still detectable. The data may indicate that the episodic nature of hormone secretion was essentially unaffected by the apallic syndrome. These results are regarded as an indication that endogenous, centrally controlled processes participate in circadian rhythms.
Diener, Knoll, Ratge, Langer and Wissei: Urinary excretion of alanine aminopeptidase and N-acetyl-/3-D-glucosaminidase 615 J. Clin. Chem. Clin. Biochem. Vol. 20,1982, pp. 615-619 Urinary Excretion of Alanine Aminopeptidase and N-Acetyl-/3-Z)-Glucosaminidase During Sequential Combination Chemotherapy 1 ) (Received December 14, 1981/April 16,1982 Summary: The urinary excretion of alanine aminopeptidase (EC 3.4.11.2) and N-acetyl-0-.D-glucosaminidase (EC 3.2.1.30) was determined in 23 patients with testicular cancer during sequential combination chemotherapy with vinblastine/bleomycin and doxorubicin/cis-platinum. Increases in enzyme excretion were more often noticed during therapy with vinblastine/bleomycin than with doxorubicin/cis-platinum. Moreover, the rises during vinblastine/ bleomycin therapy were more pronounced. The enzyme activities varied from the normal ränge up to the 14-fold of the upper limit of the normal ränge. With few exceptions, enzyme excretions returned to normal or slightly elevated values before the subsequent course. No renal insufficiency could be detected with the commonly used parameters of renal function such äs serum creatinine concentrations and creatinine clearance values, which were determined at irregulär intervals.
Ausscheidung von Alaninaminopeptidase und N-Acetyl-ß-D-glucosaminidase im Harn während sequentiell alternierender ChemotherapieZusammenfassung: Bei 23 Patienten mit Hodenkarzinomen wurde die Ausscheidung von Alaninaminopeptidase (EC 3.4.11.2) und der N-Acetyl-0-ßrglucosamimdase (EC 3.2.1.30) im Harn während der sequentiell alternierenden Chemotherapie mit Vinblastin/Bleomycin und Doxorubicin/Cisplatin gemessen. Dabei wurde festgestellt, daß Enzymanstiege unter Vinblastin/Bleomycin-Gabe häufiger auftraten und deutlicher ausgeprägt waren als unter der Doxorubicin/Cisplatin-Behandlung. Die Alaninaminopeptidase-und N-Acetyl-/3rD-glucosaminidase-Ausscheidungen erreichten Werte bis zum 14-fachen der oberen Normbereichsgrenze. Bis auf wenige Ausnahmen lagen die Werte der Enzymausscheidungen· zu Beginn eines neuen Therapiezyklus wieder im Normalbereich oder waren nur geringfügig erhöht. Die in unregelmäßigen Zeitabständen ermittelten Kreatininkonzentrationen im Serum und Kreatininclearancewerte ergaben keinen Hinweis auf eine Niereninsuffizienz während der Therapie.
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