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Biomedical subjects

U Zwergel

Publications and source records attributed to U Zwergel.

At least 19 recordsLinked to original sources
PubMed2004

Proteasome inhibitors and their combination with antiandrogens: effects on apoptosis, cellular proliferation and viability of prostatic adenocarcinoma cell cultures.

The 26S proteasome is a ubiquitin-dependent proteolytic system that has been implicated in the regulation of cell cycle progression and apoptosis. We investigated the effects of the proteasome inhibitors MG115 and PSI alone or in combination with different concentrations of the antiandrogen hydroxyflutamide on the cellular proliferation, apoptosis and viability of 10 prostatic adenocarcinoma cell cultures. Treatment with both proteasome inhibitors resulted in apoptosis induction, whereas the combinations with hydroxyflutamide generally did not, with the exception of MG115 combined with 10(-7) M hydroxyflutamide. MG115 caused a significant decrease in cellular proliferation, as did the combinations of both proteasome inhibitors with hydroxyflutamide, whereas hydroxyflutamide alone was only effective at a concentration of 10(-5) M. Cellular viability was significantly reduced when both proteasome inhibitors were combined with 10(-5) M hydroxyflutamide. Although the results varied among different cell lines, we conclude that proteasome inhibitors are able to induce apoptosis and reduce cellular proliferation. They might prove effective as antineoplastic substances in prostatic adenocarcinoma alone or in combination with antiandrogens.

Adenocarcinoma↗
PubMed2004

[Proteasome inhibitors: induction of apoptosis as new therapeutic option in prostate cancer].

New perspectives in prostate cancer genesis and putative clinical management have emerged in recent years . Apoptosis plays a major role in this environment. Proteasome inhibitors block the action of a multicatalytic proteinase complex involved in the degradation of intracellular proteins, particularly with regard to cell cycle regulation and apoptosis. Numerous in vitro studies have demonstrated the ability of these compounds to induce apoptosis and enhance the activity of conventional tumoricidal agents in many cancer cell types, including prostate cancer cells. They point out the use of these potent inhibitors as a new potential molecular approach to the therapeutic management of prostate cancer. Furthermore, the action of proteasome inhibitors has been tested in animal models and in patients with hormone refractory prostate cancer, resulting in both PSA and tumor volume decrease. PS-341 (bortezomib, Velcade) is the first proteasome inhibitor with clinical application in cancer therapy that has been used in clinical trials to date. This report reviews the current status of those papers that have tried to analyze the connection between the proteasome pathway and apoptosis. We present our results of proteasome inhibition in individual prostate cancer cell lines. Proteasomal inhibition may offer a new therapeutic access in "molecular targeting" of prostate cancer.

Animals↗
PubMed1998

[Current conservative treatment of renal colic: value of prostaglandin synthesis inhibitors].

Prostaglandin synthesis inhibitors and parasympatholytic drugs are often used as analgetics in the case of renal colic. This paper analyzes how and whether these drug effects are important for the analgetic therapy. In an animal and in a human model with acutely obstructed kidneys we found that intravenous application of Indometacine and dipyrone significantly reduces renal pelvic pressure. The parasympatholytic drug hyoscine butylbromide did not produce any change of upper urinary tract dynamics. Inhibitors of prostaglandin synthesis thus effect pressure reduction in the renal pelvis, which is necessary for analgetic therapy. In contrast, hyoscine butylbromide does not have any influence on the acute upper urinary tract obstruction; consequently its usefulness in the treatment of renal colic is rather doubtful.

English Abstract↗
PubMed1998

Long-term results following transurethral resection of the prostate.

Two subsets of a single-center study population with benign prostatic hyperplasia (n(1) = 232; n(2) = 214) undergoing transurethral resection (TUR) of the prostate (TURP 1979 and 1995) entered a retrospective study designed to examine the long-term follow-up. The actual data were assessed with a patient-addressed questionnaire. Preoperative voiding patterns did not differ significantly; postoperative micturition revealed comparable results for both groups. Mortality and TUR syndrome rates were reduced to very low levels. The most significant improvement was found in blood transfusions. The postoperative incidence of urethral stricture (1.7 vs. 1.5%) or bladder neck contracture (2.7 vs. 2.4%) were low and did not alter significantly. Urinary incontinence changed for both collectives (11.4 vs. 3.3%). Urodynamic investigations revealed that all (n = 21) but 1 of the patients with TURP 1979 had the incontinence due to different bladder dysfunctions, but not because of postoperative stress incontinence. The questionnaire about the patient's actual contentment after TURP 1979 showed 79% of the patients still satisfied, 12% neutral and 9% dissatisfied with their micturition. Overall the patients reported a generally favorable view of TURP outcome in the long-term follow-up.

Aged↗
PubMed1995

[Bladder dysfunctions in encephalomyelitis disseminata--drug and interventional therapeutic options].

Patients with disseminated encephalomyelitis have various urological presentations, ranging from pollakisuria to urge incontinence. After detailed evaluation (neuro-urological examination, urodynamic investigation) drug therapy and various interventional methods must be adapted to the individual manifestations. Patients with detrusor hyperreflexia are treated with oral anticholinergic agents (oxybutynin, trospium chloride, propiverine). Patients with urinary retention are recommended to be managed with clean intermittent (self)-catheterisation. The various interventional therapeutic options (bladder denervation, electrostimulation, local treatment with botulinum toxin) and the surgical therapy (sacral deafferentation and anterior root stimulation, bladder neck closure and cystostomy, sphincterotomy or augmentation cystoplasty) must be reserved for special cases.

Cholinergic Antagonists↗
PubMed1991

Eicosanoid synthesis in the isolated human renal pelvis, ureter and bladder.

Prostaglandin synthetase inhibitors are used for the treatment of ureteric colic. However, there is controversy regarding the mechanism of action of these drugs. In this study, differential prostaglandin synthesis in the human renal pelvis, ureter and bladder was measured using specific radioimmunoassays and gas chromatography/mass spectrometry. There was a significant quantitative predominance of the smooth muscle constrictor eicosanoids, PGF2 alpha and TXA2 over the dilatory PGE2 in tissue from all sites--renal pelvis, ureter and bladder. The results indicate that prostaglandins play a direct role in smooth muscle activity of the upper urinary tract and the inhibition of this activity with indomethacin indicates a further mode of its action in pain relief in ureteric colic.

6-Ketoprostaglandin F1 alpha↗
PubMed1991

Effects of prostaglandins and prostaglandin synthetase inhibitors on acutely obstructed kidneys in the dog.

An intact canine model was developed to study the effects of prostaglandins (PG) and prostaglandin synthetase inhibitors on acutely obstructed kidneys. Totally implanted nephrostomy tubes were placed to measure renal pelvic pressure. Complete ureteral obstruction was obtained with a Fogarty balloon catheter inflated in the distal ureter; by this method renal pelvic pressure reached 40-50 mm Hg. Renal pelvic pressure was reduced after intravenous indomethacin and dipyrone administration, whereas blood pressure showed no major changes. Exogenous prostaglandins had both immediate and contrary effects: PGE2 caused a significant decrease, whereas PGF2 alpha caused a significant increase in renal pelvic and blood pressure. The reduced rise in renal pelvic pressure appears to be the main reason for the analgesic effects of prostaglandin synthetase inhibitors. The efficiency of these drugs in the treatment of renal colic is supported by this study, that of prostaglandins cannot be proved.

Acute Disease↗
PubMed1988

Results in the use of extracorporeal piezoelectric lithotripsy (EPL) for treatment of urinary calculi.

The Piezolith 2200 as an extracorporeal shock wave lithotripter uses piezoelectrically generated, high-energy sonic impulses for treatment of urinary calculi; the shock wave generator is self-focussing. Localization of concrements is performed by means of ultrasound imaging. Treatment with the Piezolith 2200 is painless for the patient and thus possible without anesthesia and analgesia. We report on 806 cases of treatment involving a total of 572 kidneys in 567 patients (561 adults, 6 children) suffering from calculi of various sizes in the renal pelvis (n = 126), calculi in the calyces (n = 384), partial (n = 24) or full (n = 19) staghorn calculi, as well as calculi in the upper part of the ureter (n = 19). In 88% of these cases the concrements could be removed completely. Since cardiac activity is not influenced by piezoelectrically generated high-energy impulses, this procedure is particularly suited to the treatment of patients with heart problems.

Adult↗
PubMed1988

[Extracorporeal shockwave lithotripsy in the treatment of urolithiasis--experiences from a center with the Piezolith 2200 and HM3 lithotriptors].

The Piezolith 2200 allows not only a qualitatively identical treatment of urolithiasis like the HM-Dornier systems or the Siemens Lithostar, but the application of lithotriptable urinary calculi could be extended to cardiac risk patients, to patients with skeletal deformities and to those with unusual body height and weight. As the piezolithotripsy does not cause pain, treatment is possible without anaesthesia or analgesia. Combined with internal ureteral stenting by self-retaining double-J-ureteral catheter also calculi with larger stone masses can be treated advantageously by exclusive piezolithotripsy as monotherapy. Multiple treatments by the piezolithotriptor are possible because of good focussing of the shock waves and the smaller parenchymal alteration. Lithotripsy of ureteral calculi is performed in the upper and lower part of the ureter. In small calculi the retrograde introduction of an ureteral catheter armed with an "ultrasound mirror" is necessary.

Combined Modality Therapy↗