Age dependency of infradian rhythms in enzymuria of female volunteers.

The enzyme excretion of dipeptidylpeptidase IV (EC 3.4.14.5), gamma-glutamyltransferase (EC 2.3.2.2), and alanine aminopeptidase (EC 3.4.11) was pursued in three different age groups of female volunteers over a period of 70 days. The first group (1-3 years: n = 6) consisted of girls living in a children's home, the second (26-50 years, n = 7) of medical staff and the third (65-87 years, n = 7) of the inhabitants of an old-age home. Subsequent to basic statistics the excretion patterns were analyzed by spectral analysis with the maximum entropy method. The mean values of all enzymes displayed a distinct age-dependency. The highest levels of enzyme excretion were found in the early childhood. In all groups infradian changes of enzyme excretion were detected. In excretion of gamma-glutamyltransferase, longer periods between 12 and 24 days predominated during the early childhood, whereas in the middle, and in particular in the higher age, shorter dominant periods occurred more frequently. The excretion of alanine aminopeptidase displayed a similar tendency. Circaseptan periods (7 +/- 1 days) were rarely observed among the dominant periods of the maximum entropy method spectra. A correlation analysis of the individual excretion patterns revealed that the excretion of all three bush-border enzymes is most tightly correlated in the early childhood (coefficients of correlation up to 0.9). In contrast, the correlation between enzymes and creatinine excretion was low in all age groups.

Infradian rhythms of alanine aminopeptidase excretion during gentamicin therapy.

Urinary excretion of alanine aminopeptidase (EC 3.4.11.2) was examined in 30 patients (22 women, 8 men, range 38-81 years; mean age 55.4) receiving gentamicin in a therapeutic dosage, which was based on the monitored blood creatinine concentration. In general, therapy lasted 10 days. The excretion of 24 individuals displayed significant infradian rhythms with periods between 2.2 and 8.1 days. In 10 of these 24 patients (42%) a circaseptan period was detected. The high portion of circaseptan rhythms might have been induced by the detrimental effects of gentamicin on the proximal tubule and the resulting processes of reconstitution.

[ABO blood groups in patients with nephropathies]. / ABO-Blutgruppen bei Patienten mit Nephropathien.

280 patients of a centre of nephrology were with regard to their distribution of ABO and rhesus blood groups compared with a control group consisting of 4,089 donors. Female patients with pyelonephritis showed with a probability of error of less than 5% more frequently the blood group A (56.7 vs 41.8%) and more infrequently the blood group 0 (20.0 vs 39.9%). The increase of frequency of female patients of the blood group B with cystic kidneys (30.0 vs 12.6%) reached the significance level of p less than 0.1.

[Physiological influences on the enzyme elimination with urine]. / Physiologische Einflussfaktoren auf die Enzymausscheidung mit dem Urin.

It is desirable to know the factors determining the large interindividual and interindividual variation of urinary enzyme excretion rates among normal individuals to allow a better understanding of pathological states. The following factors seems to play a significant role in influencing total enzyme efflux rates: urinary flow, age, sex, biorhythms, genetic factors, hormonal situation (including pregnancy), nutrition, and physical activity.

Infradian biorhythms of enzymuria in man?

The temporal courses of dipeptidyl peptidase IV gamma-glutamyltransferase and alanine aminopeptidase were followed over 70 days in the morning urine of 15 healthy persons. Subsequent to basic statistical analysis a two-step procedure was performed, including spectral analysis and the fit of a cosine function by non-linear regression. The excretion of the 3 enzymes followed an infradian biorhythm with a mean period length of 10.04 for dipeptidyl peptidase IV, 13.34 for gamma-glutamyltransferase and 10.17 for alanine aminopeptidase. In addition to the basic rhythmic process described by the fitted cosine functions, in most of the enzyme patterns steap peaks of very high excretory activity appeared which was verified in repeated measurements. These infradian biorhythms with changes in the range of 100% and more, as well as their interindividual variations, have to be considered in assessing the excretion of enzymes.

[Urinary enzymes in research and in clinical medicine. Report on a symposium of the Humboldt-Universität Berlin and the Bezirkskrankenhaus Frankfurt/Oder in Frankfurt/Oder, 22-25 April 1987]. / Harnenzyme im Experiment und in der Klinik. Bericht über ein Symposium der Humboldt-Universität Berlin und des Bezirkskrankenhauses Frankfurt/Oder in Frankfurt/Oder (DDR), 22.-25. 4. 1987.

The symposium was dedicated exclusively to the subject of urine enzymes. Thirty nine lectures were given, in which 58 participants from 10 countries presented and discussed our present state of knowledge in the field of urine enzyme diagnosis, covering all aspects from fundamental research to its clinical application. This report summarizes the essential points of interest that arose from the lectures and discussions.

[Renal dipeptidylpeptidase IV excretion in drug-induced kidney changes]. / Renale Dipeptidylpeptidase-IV-Ausscheidung bei medikamenteninduzierten Nierenalterationen.

The course of the excretion of dipeptidyl-peptidase IV (DP IV)-alanine aminopeptidase, beta-glucuronidase and total protein with the urine was investigated during the treatment of 11 patients with pyelonephritis with gentamicin, after application of a renal radiographic contrast medium in 7 patients with arterial hypertension and after regional perfusion of an extremity in 10 patients with malignant melanoma. In the reference group in male test persons with 147.0 nmol/s X l a higher DP IV activity in the urine was recognized than in the female test persons (100.0 nmol/s X l). After application of the drugs a rhythmically intermitting increased excretion of all enzymes mentioned develops. The study confirms the usuability of the DP IV-activity for enzymological investigations of the urine.

[Urinary enzyme excretion in diseases of the internal organs]. / Harnenzymausscheidung bei Erkrankungen der inneren Organe.

In a survey the present possibilities are outlined to get knowledge about diseases of inner organs with the help of enzyme determinations in the urine. Here it is remarkable that changes of the enzyme excretion appear not only in renal disease with acute renal failure, pyelonephritis, glomerulonephritis, renal infarction and nephroptosis but are also to be observed in primarily extrarenal diseases such as diabetes mellitus, hyperthyroidism, thesaurismoses, myocardial infarction, hypertension, acute pancreatitis, epidemic hepatitis, liver cirrhosis, obstructive jaundice and rheumatoid arthritis. The causes of the changes of enzyme excretions are various. Since enzymes of different origin and localisation behave themselves variably, the simultaneous determination of a brush border marker (e.g. alanine aminopeptidase), a lysosomal enzyme (e.g. beta-glucuronidase or N-acetyl glucosaminidase) and a low molecular enzyme (e.g. lysozyme) is of use for the recognition of renal alterations. By the control of activities of urinary enzymes it is possible to get without risk informations about pathobiochemical processes in the kidney which are not to be gained by means of other methods.

[Renal enzyme excretion in tumors and tumor therapy]. / Renale Enzymausscheidung bei Tumoren und Tumortherapie.

None of the hitherto investigated enzymes of the urine can be used as marker for the proof of tumours. Hopeful starts in this respect are to be seen in an increased beta-glucuronidase excretion and in a decreased gamma-glutamyl transpeptidase excretion as well as in an increased LDH5/LDH1 ratio. The lysozyme excretion with the urine gives important references to the differential diagnosis, the assessment of the prognosis and therapy of acute leucoses. An importance obtained enzyme determinations in the urine for the clarification of pathobiochemical processes of the alteration of the kidney by neoplasms, tumour-lysis-syndromes, cytostatics, tumour radiation and operations of tumours. Courses of enzyme excretion during tumour therapy which as a rule show a rhythmic hyperenzymuria allow conclusion to the moment of the flow the catabolic products of the tumour at the kidney and to the different reaction of the tubular epithelium to these substances.

[Drug induced nephropathy and enzymes of renal origin in the urine]. / Medikamenteninduzierte Nephropathie und Enzyme renalen Ursprungs im Harn.

A report is given on the excretion of the renal enzymes alaninaminopeptidasis (AAP), N-acetyl-beta-D-glucosaminidasis (NAG), beta-glucoronidasis (GBC) and alpha-galactosidasis (GAC) in urine after administration of Gentamycin, Cephalotin, Dextran, Carbencillin or combinations of these medicaments. Moreover the effective level of Gentamycin in the urine was measured after isolated administration of Gentamycin. A rhythmic excretion of ciliated-border and lysomal enzymes was observed. Gentamycin was also rhythmically excreted with the urine. It is assumed that this reflects cyclic changes in the cells of the renal tubule. Under long-term administration of Gentamycin or Dextran the excretion of enzymes already reduced during therapy. This was interpreted as an adaptation of the kidney to the medicament. On the other hand there are combinations of medicaments whose effect on the epithelium of the renal tubule is potentiated.

[Aminoglycoside nephropathy]. / Aminoglykosidnephropathie.

Aminoglycosides lead to an increase of number and size of secondary lysosomiotics in the cells of the renal size of secondary lysosomes in the cells of the renal tubuli. Myeloid bodies appear in the lysosomes. As a sequel of the aminoglycoside antibiotics accumulated in the kidney a rhythmic change of the function of the cells of the tubuli with hyperenzymuria, decreased reabsorption of low molecular weight proteins, decreased concentration of urine and decreased glomerular filtration develops. Despite continued drug exposure these deviations are reversible. Simultaneous application of cephalotin, dextran or furosemid increase the toxic effect. A summarizing hypothesis concerning the aminoglycoside-induced nephropathy is presented which takes into consideration the specific receptor binding of the aminoglycosides at the membrane of the tubulus, their accumulation in the lysosomes and their ways in the cell of the tubulus. The lysosomes are regarded as primary working point of the aminoglycosides.

[Hemofiltration of lysozyme in dialysis patients]. / Die Hämofiltration des Lysozyms bei Dialysepatienten.

With the help of the haemofiltration on the capillary dialysator CDAK 4 the behaviour of lysozyme (muramidase) was investigated in 20 dialysis patients. In 6 of 55 cases a measurable lysozyme concentration in the haemofiltrate was found. A relation to the size of the serum lysozyme level could not be established. The influence of defective capillaries is discussed. Despite the in most cases not measurable lysozyme concentrations in the haemofiltrate a decrease of the serum lysozyme level taking place parallel to creatinine could be proved during dialysis. Examinations of the influence of the renal rest function in dialysis patients with a rest diuresis resulted in a lower lysozyme concentration in the serum than in patients with complete anuria. These findings allow conclusions to the behaviour of low-molecular proteins in the kidney of dialysis patients and to their losses on the dialysis membrane.

[Experience with sisomicin in pediatrics (author's transl)]. / Erfahrungen mit Sisomicin in der Pädiatrie.

Sisomicin, an aminoglycoside antibiotic, is especially effective against Escherichia coli, Klebsiella, Enterobacter, Citrobacter, Serratia, indole-positive and indole-negative Proteus species, Pseudomonas aeruginosa, Salmonella and Staphylococcus aureus. It has a bactericidal action. Although sisomicin is similar to the other aminoglycoside antibiotics, there is not complete cross-resistance to them. Our own pharmacokinetic investigations showed that a dose of 2--3 mg/kg body weight of sisomicin twice daily is necessary in the neonatal period. Infants should be given 2.5 mg/kg body weight three times daily, and school children 1.5--20 mg/kg body weight, likewise three times daily. Excretion of sisomicin in the urine is lower in children than in adults, amounting within 24 hours to only 10--20% in newborns, and 30--40% in school-children. Sisomicin induces excretion of some enzymes in higher quantities from the tubular part of the kidneys, especially alaninaminopeptidase. A report is given on 58 patients, especially newborns and prematures, who were treated for about seven days with sisomicin. The results obtained with a wide variety of infections (such as omphalitis, aspiration of amniotic fluid with broncho-pneumonia, phlegmons of the galea, and also pyelonephritis and mucoviscidosis with pulmonary complications) can be described as good, with a success rate of 85%. On only seven occasions were insignificant transitory side-effects, such as slight increase in transaminases, toxic-allergic exanthema and pain in the region in injection, observed.