Oral administration of taurolidine ameliorates chronic DSS colitis in mice.

Taurolidine (TRD) has antimicrobial and anti-inflammatory properties. However, the anti-inflammatory effects of TRD in inflammatory bowel diseases (IBD) have not been investigated. Here, we have analyzed the toxicity of TRD after oral long-term application in mice and examined the impact of oral TRD in a dextran sulfate sodium (DSS) model of experimental colitis. Female C57/BL6 mice received TRD in various concentrations (0.1% to 0.4%) for 60 days. Toxicity was evaluated by use of a disease activity index (DAI) and histological examination of major metabolic organs. Furthermore, the impact of 0.2% TRD on a chronic DSS colitis was examined by daily DAI, histological crypt damage score (CDS), bacterial translocation into mesenteric lymph nodes (MLN), and colonic expression of tumor necrosis factor (TNF) alpha, transforming growth factor (TGF) beta, interleukin (IL)-1beta, IL-6, cytochrome oxidase (COX)-2, and monocyte chemotactic protein (MCP)-1 by real-time polymerase chain reaction (PCR). Oral TRD administration for 60 days was well tolerated by the animals and did not show any toxic effects in terms of DAI and histological changes. TRD treatment of DSS colitis led to increased survival of 100%, compared to 33% in the untreated colitis group (p < or = .005). Clinical amelioration was mirrored by significantly reduced DAI and CDS in the TRD treated colitis. Colonic cytokine expression and bacterial translocation into MLN showed no differences between both groups. We thus report for the first time that oral application of TRD results in amelioration of an experimental IBD model. We hypothesize direct intraluminal antimicrobial effects of TRD as well as anti-inflammatory effects during the acute phase of DSS colitis.     

Treatment of type B aortic dissection: endoluminal repair or conventional medical therapy?

OBJECTIVE: To evaluate the mid-term results of endovascular stent-grafting for type B aortic dissection, in comparison with those of standard medical therapy in uncomplicated cases. METHODS: Between January 1999 and 2004, among 56 patients (mean age 59.5+/-11.5 years) with type B aortic dissection, hypotensive medical therapy was the only treatment in 28 uncomplicated cases, (group A), while stent-graft implantation was performed in 28 patients with uncontrolled hypertension, persistent pain or evidence of dissection progression or complication (group B). In 14 cases (50%) the procedure was performed in an acute setting. Stent-grafting procedures were monitored with intraoperative trans-esophageal echocardiography and cine-angiography. CT scan and trans-esophageal echocardiography were performed before hospital discharge, at 6 and 12 months and then yearly. RESULTS: Follow-up (range 1-61 months, average 18.1+/-16.9 months) was 100% complete. In-hospital mortality was 10.7% (three patients, all belonging to Group B; P=0.24). No spinal cord injuries were observed. Early endoleak occurred in one patient (3.5%). Mid-term mortality was lower in Group B, although the difference was not significant (10.7 versus 14.3% in Group A, P=0.71). Follow-up CT scans evidenced complete thrombosis of the false lumen in 75% cases in Group B, 10.7% in Group A (P=0.0001), and an aneurismal dilatation of the descending aorta in 3.5% cases in Group B, 28.5% in Group A (P=0.02). CONCLUSIONS: Although with still considerable early mortality, endovascular stent-graft implantation is an effective option for the treatment of complicated type B aortic dissection. Endovascular treatment achieved a better mid-term fate of the descending thoracic aorta than medical therapy alone, even in patients with worse preoperative conditions.     

Towards improved clinical characterization of Leber congenital amaurosis: neurological and systemic findings

Leber congenital amaurosis (LCA) is the most severe form of inherited retinal dystrophy that presents in infancy. LCA is both clinically and genetically heterogeneous. The aim of our study was to clarify the clinical aspects of LCA and to contribute to improved characterization of the disorder. We studied 40 children affected by LCA (mean age at first observation: 19 months, range: 8-50 months), who underwent a comprehensive evaluation that included: neurophthalmological evaluation, electroretinogram (ERG), and visual evoked potentials (VEPs), general and neurological examinations, developmental assessment using scales for visually impaired children, neuroradiological examinations, hepatic and renal function and metabolic investigations, brainstem auditory evoked potentials (BAEPs), EEG, and hand radiographs. Analyses of known LCA genes are ongoing. The subjects are still being followed up at 6-/12-month intervals. All the subjects fulfilled De Laey's criteria for LCA. The neurological examination was abnormal in 31 cases (hypotonia, ataxia with/without associated cerebellar signs). Cognitive development was normal in 24 cases, borderline in five, and subnormal in 11. Mild and nonspecific alterations on MRI were present in seven cases, and "molar tooth" sign in four; all the others had a normal neuroradiological picture. Among the subjects presenting with neurological signs, a subgroup (13 patients) emerged that was characterized by systemic (skin, kidney, liver) involvement. Our data confirm that LCA is a heterogeneous entity that can present as an isolated ocular manifestation, or in association with neurological and systemic abnormalities and support the need for a multidisciplinary approach to this entity and for genotype-phenotype studies.     

Immunization of rabbits with a modified vaccinia Ankara recombinant virus bearing the HIV envelope antigen on its outer membrane

Modified vaccinia virus Ankara (MVA) is a highly attenuated strain of vaccinia virus, which propagates efficiently in chicken embryo fibroblasts but fails to complete its growth cycle in many types of mammalian cells. We constructed a recombinant virus MVA/EK5, which has a chimeric gene encoding for the extracellular domain of the HIV envelope protein fused to the cytoplasmic and transmembrane domain of the B5R protein of vaccinia virus. The fused HIV envelope antigen was expressed in the African green monkey kidney BS-C-1 cells infected with the recombinant virus. This virus, which had been grown in chicken embryo fibroblasts, induced in rabbits antibodies against the HIV envelope antigen, in addition to those against poxvirus.