Insulin aggregation assessment by capillary gel electrophoresis without sodium dodecyl sulfate: Comparison with size-exclusion chromatography.

Size-exclusion chromatography (SEC) is a method of choice for the analysis of protein aggregates in pharmaceuticals. The United States and European Pharmacopoeias currently use a SEC method with an acidic pH mobile phase to assess the content of aggregates in insulin formulations. In this article, we analyzed aggregated human insulin samples and demonstrated that both methods under neutral conditions, namely neutral pH SEC (nSEC) and capillary gel electrophoresis (CGE), yield to similar aggregate content contrary to SEC under acidic conditions (aSEC). aSEC showed polymeric complexes that were not observed in nSEC and CGE. During method development, the effect on SEC profiles of arginine and acetonitrile were highlighted. In CGE, the effect of SDS on disruption of non-covalent insulin aggregates was confirmed and the benefit of sodium deoxycholate addition in sieving gel was discussed. The three methods were applied to the analysis of an insulin formulation and similar results to those obtained for human insulin as raw material were observed. Finally, the CGE method was used to study the stability of human insulin under different storage conditions. In view of the obtained results one may question the relevance of the current pharmacopoeia method to study insulin aggregates by emphasizing the importance of the mobile phase composition and pH in SEC. The new CGE method developed is an easy method for studying non-covalent aggregates of insulin, which could be applied to other proteins.

[Anatomic-clinical presentation. Testicular teratocarcinoma with thoracic-abdominal adenopathy]. / Présentation anatomo-clinique. Térato-carcinome testiculaire avec adénopathies thoraco-abdominales.

This case report of a young man with a testicular germ cell-teratoma tumor illustrates the necessity of a multidisciplinary sequential approach to ensure chance of cure. The outcome of patients with advanced germ cell tumor depends on the optimal clinical management. Residual masses are frequent, and their histology can be different than the initial one (i.e., only residual mature teratoma cells or necrosis-fibrosis). Therefore a second surgery on residual masses with curative intent, may be important to optimalize the treatment and follow up.

[Recurrent urethral stenosis treated with a Urolome Plus stent implantation: intermediate multicenter follow-up]. / Sténose urétrale récidivante traitée par implantation d'un stent Urolume Plus: suivi multicentrique à moyen terme.

We present the medium-term results of 33 patients treated with Urolume Plus urethral stent between August 1990 and June 1996 in 9 Belgian and Luxembourg centers. They all had previous treatments for bulbo-membranous urethral stricture, but without sustained benefit (dilatation, internal urethrotomy, or/and urethroplasty). The mean age of the stricture was 5.4 years (+/- 4). The stent was inserted easily during a short hospitalisation. Median time of follow-up is two years (6 months to 4 years). Maximum flow rate at last follow-up was 20.7 ml/sec (+/- 7), and 83.3% of the patients were satisfied with the stent. In 70% of the cases, the stent achieved its purpose of maintaining a good urethral lumen. In 5 patients (15.15%), stricture recurred inside the stent and in 2 patients (6.06%) a new stricture appeared on another site. Among these 7 patients, 5 were satisfactorily treated by endoluminal resection (4 cases) or dilatation (1 case). There were 2 real failures (= 6%): one patient who has refused any complementary endoscopic treatment and the other one who is still undergoing repeated urethral dilatations. Having respected the right indications for this device, we are satisfied of the results. It is a good alternative after failure of other treatments for bulbar-membranous stricture.