Interactive Effects of Copper-Doped Urological Implants with Tissue in the Urinary Tract for the Inhibition of Cell Adhesion and Encrustation in the Animal Model Rat.

The insertion of a ureteral stent provides acute care by restoring urine flow and alleviating urinary retention or dysfunction. The problems of encrustation, bacterial colonization and biofilm formation become increasingly important when ureteral stents are left in place for a longer period of time. One way to reduce encrustation and bacterial adherence is to modify the stent surface with a diamond-like carbon coating, in combination with copper doping. The biocompatibilities of the Elastollan® base material and the a-C:H/Cu-mulitilayer coating were tested in synthetic urine. The copper content in bladder tissue was determined by atomic absorption spectroscopy and in blood and in urine by inductively coupled plasma mass spectrometry. Encrustations on the materials were analyzed by scanning electron microscopy, energy dispersive X-ray spectroscopy and Fourier transform infrared spectroscopy. A therapeutic window for copper ions of 0.5-1.0 mM was determined to kill bacteria without affecting human urothelial cells. In the rat animal model, it was found that copper release did not reach toxic concentrations in the affecting tissue of the urinary tract or in the blood. The encrustation behavior of the surfaces showed that the roughness of the amorphous carbon layer with the copper doping is probably the causal factor for the higher encrustation.

Prevention of Encrustation on Ureteral Stents: Which Surface Parameters Provide Guidance for the Development of Novel Stent Materials?

Encrustations of ureteral stents are one of the biggest problems with urological implants. Crystalline biofilms can occur alone or in combination with bacterial biofilms. To identify which surface parameters provide guidance for the development of novel stent materials, we used an in vitro encrustation system. Synthetic urine with increasing pH to simulate an infection situation was pumped over the polymer samples with adjusted flow rates at 37 °C to mimic the native body urine flow. Chemical surface features (contact angle, surface charge), as well as encrustations were characterized. The encrustations on the materials were analyzed quantitatively (dry mass) and qualitatively using scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), and Fourier transform infrared spectroscopy (FTIR). The aim of this comparative study was to identify crucial surface parameters that might predict the quantity and type of mineral deposits in vitro and provide guidance for the development and screening of new polymer-based biomaterials for ureteral stent design. For the first time, we could identify that, within the range of our polymers, those materials with a slight hydrophilicity and a strong negative zeta potential (around -60 mV) were most favorable for use as ureteral stent materials, as the deposition of crystalline biofilms was minimized.

Bioavailability investigation of two different oral formulations of citalopram, a so-called 'second generation' antidepressant drug.

Citalopram (CAS 59729-33-8) belongs to the so-called 'second generation' antidepressant drugs and is used for the treatment of patients with major depression or other depressive disorders. In the present study, two different oral citalopram formulations (Citalopram-ratiopharm film-coated tablets as test preparation and tablets of a reference preparation distributed in Germany) were investigated in 20 healthy volunteers in order to prove bioequivalence between both preparations. A single 40 mg oral dose was administered according to an open, randomised, two-period cross-over design in the fasted state. Blood samples for determination of citalopram plasma concentrations were collected at pre-defined time points up to 168 h following drug administration. A wash-out period of 21 days separated both treatment periods. Citalopram plasma concentrations were determined by means of a validated HPLC method with fluorescence detection. Maximum plasma concentrations (Cmax), of 34.77 ng/ml (test) and 34.42 ng/ml (reference) were achieved. Areas under the plasma concentration-time curve (AUC0-infinity) of 1,719.69 ng*h/ml (test) and 1,725.71 ng*h/ml (reference) were determined. The results showed nearly identical rate and extent of drug absorption. Also further pharmacokinetic parameters were well comparable with each other. Thus, tmax showed values of 3.29 h (test) and 3.77 h (reference). The plasma elimination half-life (t1/2) was 42.50 h (test) und 44.46 h (reference). Both primary target parameters Cmax and AUC0-infinity were tested parametrically by analysis of variance (ANOVA). Bioequivalence between test and reference preparation was demonstrated since for both parameters AUC and Cmax the 90 % confidence intervals of the T/R-ratios of logarithmically transformed data were in the generally accepted range of 80 %-125 %.