[Functional results after temporary continuous drainage of the hypocontractile bladder. The potential rehabilitation of the detrusor]. / Funktionelle Ergebnisse nach temporärer Dauerableitung der hypokontraktilen Blase. Zur Rehabilitationsfähigkeit des Detrusors.

BACKGROUND: Impaired bladder emptying is a common problem in older people and a challenging task in treatment. Conservative and medical treatment options have shown beneficial effects on micturition; however, in a substantial number of patients the effectiveness of these therapies is disappointing. In the end the decompensated bladder needs indwelling catheterisation. To study the effects on the detrusor function, we analysed the urodynamic data of 31 patients during long-term bladder drainage retrospectively. PATIENTS AND METHODS: All 17 female and 14 male patients showed impaired detrusor contractility, enlarged bladder capacity, decreased sensitivity and a high post-void residual urine volume (PVR). After exclusion of an acute pathology, the patients were treated continuously with a suprapubic catheter for an average of 13.1 weeks. By urodynamic measurements before and after the drainage period, we analysed the filling parameters, pressure-flow patterns, PVR and detrusor contractility. RESULTS: At the end of the drainage period, significant changes in the detrusor function were obvious. Compared with the pre-treatment situation, the bladder volume at first desire to void decreased from 306.92 ml to 281.7 ml and the maximum bladder capacity from 691.8 ml to 496.8 ml, respectively. The compliance of the detrusor muscle diminished in the same period of time from 65.6 ml/cmH2O to 51.8 ml/cmH2O. The PVR dropped by 227.2 ml in average. The maximum flow rate was 9.4 ml/s, and the maximum detrusor pressure increased slightly up to 23.6 cmH2O. CONCLUSION: The continuous drainage of the bladder results in significant changes in the motoric as well as sensoric detrusor function. The reduced bladder capacity and the decreased PVR might be indications of a regenerating process of the detrusor. The long-term drainage of the bladder shows beneficial and therefore therapeutic effects. It still remains to be investigated on a functional as well as structural basis to what extent age, gender and pathogenesis influences the rehabilitation of the detrusor.

Studies on N4-(2-deoxy-D-pentofuranosyl)-4,6-diamino-5-formamidopyrimidine (Fapy.dA) and N6-(2-deoxy-D-pentofuranosyl)-6-diamino-5-formamido-4-hydroxypyrimidine (Fapy.dG).

Exposure of DNA to oxidative stress produces a variety of DNA lesions including the formamidopyrimidines, which are derived from the purines. These lesions may play important roles in carcinogenesis. We achieved the first chemical syntheses of a monomeric form of Fapy-dA (1) and oligonucleotides containing this lesion or Fapy-dG at a defined site. Monomeric Fapy-dA readily epimerized at 25 degrees C in phosphate buffer (pH 7.5). The beta-anomer was favored by a ratio of 1.33:1.0, and equilibration was achieved in less than 7 h. Deglycosylation of Fapy-dA in the monomer follows first-order kinetics from 37 to 90 degrees C. The rate constants for deglycosylation of Fapy-dA in the monomeric and oligonucleotide substrates were measured at a common temperature (55 degrees C) and found to be the same within experimental error (t(1/2) = 20.5 h). Implementation of the activation parameters measured for the deglycosylation of 1 indicates that the half-life for deglycosylation of Fapy-dA at 37 degrees C is approximately 103 h. Analysis of the rate constant for deglycosylation of Fapy-dG in an oligonucleotide, revealed that this lesion is approximately 25 times more resistant to hydrolysis than Fapy-dA at 55 degrees C. These results indicate that Fapy-dA and Fapy-dG will be sufficiently long-lived in DNA so as to warrant investigation of their genotoxicity, and both anomers will be present during this time.

Synthesis and characterization of oligonucleotides containing formamidopyrimidine lesions (Fapy.dA, Fapy.dG) at defined sites.

The preparation of oligonucleotides containing Fapy.dA (N4-(2-Deoxy-alpha,beta-D-erythro-pentofuranosyl)-4,6-diamino- 5-formamidopyrimidine) and Fapy.dG (N6-(2-Deoxy-alpha,beta-D-erythro-pento-furanosyl)-2,6- diamino-4-hydroxy-5-formamido-pyrimidine) at defined sites was achieved by introducing the lesions as dinucleotide phosphoramidites. Oligonucleotides as composed of as many as 36-nucleotides were prepared by solid-phase synthesis and/or a combination of chemical synthesis and enzymatic ligation. Oligonucleotides containing non-hydrolyzable analogues were also prepared. Oligonucleotides containing these modified nucleotides were characterized by a variety of chemical and biochemical methods.