Bioartifizielle Materialien in der Urologie

The scope of our research is the development of polymer-based bioabsorbable stents for urologic applications and in vitro testing of tissue reactions of cultured ureteral and urethral segments induced by implanted polymer stent prototypes. For these purposes a tissue cultivation model was developed using selected techniques of tissue engineering. Essential advantages of degradable over nondegradable urethral stents are elimination of the adverse extraction of epithelialized stents and the potential for recovery of organ-specific functionality. Moreover, the biocompatibility of a degradable urethral stent could potentially reduce the risk of restenosis due to hyperplasia and could be used, even repeatedly, for the treatment of a number of subvesical obstructions. For the treatment of tumor-induced strictures, application of degradable polymer stents coated with cytostatic drugs may be possible. The mechanical effect of the drug-loaded stent as a “place holder” could be complemented by adjuvant or palliative approaches such as local chemotherapy. We have developed and tested in vitro a degradable urethral stent incorporated with the model drug methotrexate for local drug delivery (LDD) by diffusion and during stent degradation.     

Eye injuries caused by vesicatory insects

Ocular injuries by vesicatory insects appear exceptional and the authors have not found any reports in the literature. Cantharidine, with toxicity comparable to that of mustard gas, can be present in many species of coleoptera. It results in progressive corneal necrosis ending in ocular perforation in 30 days. The necrotic process persists with long duration because this material is not broken down. It provokes deep ocular injuries (cristalline lens). The inflammatory reaction is severe with acute refractory hypertension. There exists no antidote, only prevention is useful. Emergency penetrating keratoplasty with anterior chamber lavage should help eliminate the toxin. In daily practice, the authors observe similar but less serious injuries; they think that they could be due to dust rich in vesicatory insect debris or their secretions.     

Contribution of Blockade of the Noradrenaline Carrier to the Increase of Extracellular Dopamine in the Rat Prefrontal Cortex by Amphetamine and Cocaine

This study was performed to investigate the relative role of noradrenaline (NA) and dopamine (DA) carrier blockade in the effects of psychostimulants on DA transmission in the rat prefrontal cortex (PFCX). To this end, changes of extracellular DA and NA in the PFCX and of extracellular DA in the nucleus accumbens (NAc) were measured following the administration of amphetamine and cocaine, which are known to bind to both DA and NA carriers, or GBR 12909, a selective DA carrier blocker. After non-intravenous injection, amphetamine (0.25 and 0.5 mg/kg, s.c.) and cocaine (5 and 10 mg/kg, i.p.) increased extracellular DA in the PFCX to a larger extent than in the NAc, while the reverse applied to GBR 12909 (2.5 and 5 mg/kg, i.p.). These differences were obtained in spite of the fact that the three drugs elicited at each dose level a similar peak increase of extracellular DA in the NAc. Amphetamine and cocaine also increased extracellular NA in the PFCX and this effect was quantitatively similar to that on extracellular DA in the same area. Intravenous doses of cocaine and GBR 12909, corresponding to those which maintain self-administration in the rat, while equieffective in raising extracellular DA in the NAG, had different effects on extracellular DA in the PFCX. In fact, in contrast to cocaine, GBR 12909 increased extracellular DA in the PFCX to a lesser extent than in the NAc or did not modify it at all. The peak increase of extracellular DA in the PFCX was highly correlated to that of NA in the same area but was poorly correlated to the increase of extracellular DA in the NAc. These results suggest that amphetamine and cocaine increase extracellular DA in the PFCX largely through the blockade of the NA carrier. Direct evidence for this hypothesis was provided by the observation that, when the NA carrier was blocked by reverse dialysis of the PFCX with desipramine (1 μM), cocaine and GBR 12909 lost their differences in the ability to increase extracellular DA in the PFCX.     

Cytomegalovirus retinitis in advanced HIV-infected patients treated with protease inhibitors: incidence and outcome over 2 years

We prospectively studied the incidence of cytomegalovirus (CMV) retinitis in 93 patients treated with highly active antiretroviral therapy (HAART) containing a protease inhibitor (PI), during a median follow-up period of 24 months. The median initial CD4+ count was 22 cells/microl (range, 1-311 cells/microl), and the median plasma HIV viral load was 5.1 log10 copies/ml (range, 2.4-6.4 log10 copies/ml). The fundus was examined monthly in patients with a history of CMV retinitis or an initial CD4+ count <50 cells/microl and every 3 months in the other patients. Of patients with previously controlled CMV retinitis, 1 of 7 relapsed. In addition, 6 of 59 patients with a CD4+ count <50 cells/microl and no history of CMV retinitis before starting PI therapy developed CMV retinitis. Of them, 3 had at least one relapse during follow-up. CD4+ counts were <40 cells/microl at the time of primary or recurrent CMV retinitis, except in two cases (147 cells/microl and 203 cells/microl). In conclusion, the incidence of CMV retinitis was 0.091 per patient-year among study subjects with advanced HIV infection who were receiving HAART (95% confidence interval [CI], 0.037-0.145). The time to progression of CMV retinitis (mean, 215 days; 95% CI, 113-317 days) was longer than reported before widespread use of PIs.     

A high frequency of the A30, B18, DR3, DRw52, DQw2 extended haplotype in Sardinian celiac disease patients: Further evidence that disease susceptibility is conferred by DQ A1*0501, B1*0201

This study characterizes by serological and molecular methods the HLA class I and class II alleles in a group of celiac disease children, their parents and a control group of Sardinian descent. We found the DR3-DQw2 haplotype in all patients which was, in almost all cases (84%), associated with the HLA-A30, B18, DR3, DRw52, DQw2 extended haplotype named "Sardinian haplotype" because of its frequency (12-15%) in this Caucasian population. This is the first time that this DQw2-linked haplotype has been reported with such a high frequency in CD. However, no different distribution of "Sardinian haplotype" was found comparing CD patients with 91 haplotyped DQw2-positive controls. This finding indicates that the DQw2 antigen in Sardinians is almost always associated with the A30, B18, DR3, DRw52, DQw2 extended haplotype. The DQA1 and DQB1 second exon sequence analysis of the B18,DR3 and B8,DR3 haplotypes showed the DQA1*0501 and DQB1*0201 alleles which shared the already published sequences. DPB1 subtyping showed the DPB1*0301 allele more frequently (p less than 0.005) in CD patients but this difference was no longer significant when patients and controls, both heterozygous for the DR3-DQw2 haplotype, were compared. We suggest that the divergent HLA extended haplotypes and DP allele associated with CD, described in different Caucasian populations, can be explained by the particular DQw2 linkage disequilibrium in each population.     

MPTP‐induced dopamine neuron degeneration and glia activation is potentiated in MDMA‐pretreated mice

Clinical observations report a greater propensity to develop Parkinson's disease (PD) in amphetamine users. 3,4‐Methylenedioxymethamphetamine (MDMA; “ecstasy”) is an amphetamine‐related drug that is largely consumed by adolescents and young adults, which may have neuroinflammatory and neurotoxic effects. Here, the objective was to evaluate in mice whether consumption of MDMA during adolescence might influence the neuroinflammatory and neurotoxic effects of 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP), a toxin known to induce PD in humans. The activation of astroglia and microglia by glial fibrillary acidic protein (GFAP) and complement receptor type 3 (CD11b) immunohistochemistry and the degeneration of dopaminergic neurons by tyrosine hydroxylase (TH) immunohistochemistry were evaluated. MPTP (20 mg/kg × 4) was administered to mice treated from ages 8 weeks to 17 weeks with MDMA (10 mg/kg twice daily, two times a week). In mice that were chronically treated with MDMA, administration of MPTP induced a higher microglial and astroglial response in both the striatum and the substantia nigra pars compacta (SNc) compared with vehicle‐treated or vehicle + MPTP‐treated mice. Inflammatory changes were associated with a decrease in TH immunoreactivity in the SNc of MDMA‐treated mice and with a further decrease in the striatum and the SNc of MDMA + MPTP‐treated mice compared with vehicle‐treated, MDMA‐treated, and MPTP‐treated mice. The results demonstrate that chronic administration of MDMA during late adolescence in mice exacerbates the neurodegeneration and neuroinflammation caused by MPTP, suggesting that MDMA may constitute a risk factor for dopaminergic neuron degeneration. © 2013 International Parkinson and Movement Disorder Society     

The phenol red thread first results for the assessment of the cut-off value in ocular sicca syndrome

PURPOSE: To determine the cut-off value of the phenol red-impregnated thread test (Zone-Quick((R)), Menicon trade mark ) for the diagnosis of ocular sicca syndrome using the ROC (receiver operating characteristic) procedure and to estimate the agreement with the Schirmer I test (without anesthetics). MATERIAL: and methods: Fifty-four consecutive patients (including 50 females) with dry eyes, presumably related to an immune disorder, were recruited on the basis of subjective ocular symptoms and medical history (sicca syndrome). Both the phenol red thread (PRT) test and the Schirmer I test (testing periods, 15s and 5min, respectively) were performed in both eyes in random order. Only the lowest result for each test was used in statistical analyses. The same procedure was applied to 29 normal volunteers (no subjective symptoms). The patient and the control groups were matched for age and gender (mean age, 58.1 and 59.6, respectively). RESULTS: The ROC procedure showed that a cut-off value of 12mm in the PRT test provided the best ratio between sensitivity and specificity (56% and 69%, respectively) for the detection of dry eyes. Using this threshold, the agreement with the Schirmer I test was highly significant (kappa test; P<10(-3)). However, discordant results were observed in 32% of subjects. CONCLUSION: Giving a cut-off value at 12mm, the sensitivity and specificity of the PRT are 56% and 69%, respectively. Even if the agreement with the Schirmer I test is highly significant, 32% of patients have discordant results. These two methods of functional assessment of tear secretion are therefore complementary and further studies remain necessary to better understand the place of both tests in clinical practice.     

Bilateral diffuse uveal melanocytic proliferation associated with systemic carcinoma: two case reports

Diffuse uveal melanocytic proliferation is a rare paraneoplastic syndrome resulting in rapid bilateral visual loss in patients with systemic carcinoma, caused by proliferation of benign melanocytes within the choroid and the ciliary body. More often visual impairment is due to retinal detachment and cataract. The authors report two cases of presumed diffuse uveal melanocytic proliferation. The first patient was a 74-year-old man with a history of colic carcinoma and hemangioendothelioma of the liver who presented with bilateral multiple nevi of the choroid and extrascleral melanic nodule. The second patient was a 59-year-old woman who presented bilateral multiple nevi of the choroid and a history of carcinoma of the thyroid treated by thyroidectomy 2 years before. There was no evidence of systemic melanoma in either patient. Our two patients showed slow progression with no visual impairment and a longer survival than those described in the literature.