Early Host Tissue Response to Different Types of Vascular Prostheses Coated with Silver Acetate or Vaporized Metallic Silver

ObjectivesIn vascular surgery, the infection of prosthetic vascular grafts represents a serious life-threatening complication. Due to the increasing resistance of hospital micro-organisms to standard antibiotic therapies, maximum effort should be put in the primary prevention of such infections. For this purpose, grafts may be coated with different antibacterial silver formulations. In the present study the different effects of silver acetate-coating and vaporized metallic silver-coating on the vascularization and perigraft inflammation during the initial phase after implantation of Intergard Silver (IS) and Silver Graft (SG) were compared.MethodsSilver acetate-coated IS and vaporized metallic silver-coated SG were implanted into the dorsal skinfold chamber of C57BL/6 mice (n = 8 per group) to study angiogenesis and leukocyte inflammation at the implantation site by means of repetitive intravital fluorescence microscopy over a 14-day period. At the end of the in vivo experiments, apoptosis and cell proliferation in the newly developed granulation tissue surrounding the implants was analyzed by immunohistochemistry.ResultsIS exhibited an improved vascularization, resulting in a significantly higher functional capillary density when compared to SG. Moreover, the leukocyte inflammatory response to IS was less pronounced, as indicated by a reduced number of adherent leukocytes in perigraft venules. This was associated with a higher proliferative activity of the granulation tissue incorporating the IS when compared to SG. The numbers of apoptotic cells in the perigraft tissue were low and did not differ between the two groups.ConclusionSilver acetate-coated IS exhibits an improved vascularization and reduced perigraft inflammation during the first 14 days after implantation when compared to vaporized metallic silver-coated SG. This may contribute to reducing the risk of early perigraft seroma formation and subsequent infection

In Vitro Photodynamic Therapy with Chlorin e6 Leads to Apoptosis of Human Vascular Smooth Muscle Cells

Percutaneous coronary intervention has become the most common and widely implemented method of heart revascularization. However, the development of restenosis remains the major limitation of this method. Photodynamic therapy (PDT) recently emerged as a new and promising method for the prevention of arterial restenosis. Here the efficacy of chlorin e6 in PDT was investigated in vitro using human vascular smooth muscle cells (TG/HA-VSMCs) as one of the cell types crucial in the development of restenosis. PDT-induced cell death was studied on many levels, including annexin V staining, measurement of the generation reactive oxygen species (ROS) and caspase-3 activity, and assessment of changes in mitochondrial membrane potential and fragmentation of DNA. Photosensitization of TG/HA-VSMCs with a 170 μM of chlorin e6 and subsequent illumination with the light of a 672-nm diode laser (2 J/cm2) resulted in the generation of ROS, a decrease in cell membrane polarization, caspase-3 activation, as well as DNA fragmentation. Interestingly, the latter two apoptotic events could not be observed in photosensitized and illuminated NIH3T3 fibroblasts, suggesting different outcomes of the model of PDT in various types of cells. The results obtained with human VSMCs show that chlorin e6 may be useful in the PDT of aerial restenosis, but its efficacy still needs to be established in an animal model

Modifying effect of dual antiplatelet therapy on incidence of stent thrombosis according to implanted drug-eluting stent type

Aim To investigate the putative modifying effect of dual antiplatelet therapy (DAPT) use on the incidence of stent thrombosis at 3 years in patients randomized to Endeavor zotarolimus-eluting stent (E-ZES) or Cypher sirolimus-eluting stent (C-SES). Methods and results Of 8709 patients in PROTECT, 4357 were randomized to E-ZES and 4352 to C-SES. Aspirin was to be given indefinitely, and clopidogrel/ticlopidine for ≥3 months or up to 12 months after implantation. Main outcome measures were definite or probable stent thrombosis at 3 years. Multivariable Cox regression analysis was applied, with stent type, DAPT, and their interaction as the main outcome determinants. Dual antiplatelet therapy adherence remained the same in the E-ZES and C-SES groups (79.6% at 1 year, 32.8% at 2 years, and 21.6% at 3 years). We observed a statistically significant (P = 0.0052) heterogeneity in treatment effect of stent type in relation to DAPT. In the absence of DAPT, stent thrombosis was lower with E-ZES vs. C-SES (adjusted hazard ratio 0.38, 95% confidence interval 0.19, 0.75; P = 0.0056). In the presence of DAPT, no difference was found (1.18; 0.79, 1.77; P = 0.43). Conclusion A strong interaction was observed between drug-eluting stent type and DAPT use, most likely prompted by the vascular healing response induced by the implanted DES system. These results suggest that the incidence of stent thrombosis in DES trials should not be evaluated independently of DAPT use, and the optimal duration of DAPT will likely depend upon stent type (Clinicaltrials.gov number NCT00476957

Incontinence in persons with Noonan Syndrome

Objective Noonan Syndrome (NS) is an autosomal neuro-developmental disorder with a high phenotypic variability. Mutations in several genes of the RAS-MAPK signaling pathways are now known to be responsible for NS. Most of the children with NS are of average intelligence, one-third have a mild intellectual disability (ID) (IQ 50-79). So far, no studies have assessed incontinence in persons with NS. The aim of this study therefore was to investigate the prevalence of incontinence and psychological problems in persons with NS. Subjects and methods Nineteen children (5-17 years) and 10 adults (18-48 years) with NS were recruited through a German parent support group (58.6% male, mean age 15.26 years). The "Parental Questionnaire: Enuresis/Urinary Incontinence", "Encopresis Questionnaire - Screening Version" and the German version of the International Consultation on Incontinence Questionnaire - Pediatric Lower Urinary Tract Symptom (ICIQ-CLUTS) were completed by parents or caregivers to assess incontinence and lower urinary tract symptoms (LUTS). The Developmental Behavior Checklist for parents (DBC-P) or the Developmental Behavior Checklist for adults (DBC-A) were filled out to assess psychological symptoms. Results In total, 27.3% of the children (4-12 years) had nocturnal enuresis (NE), 36.4% had daytime urinary incontinence (DUI), and 11.1% had fecal incontinence (FI). Only one adolescent (13-17 years) had NE (14.3%) and one young adult (18-30 years) had FI (11.1%); 36.4% of the children, 33.3% of the adolescents and 12.5% of young adults had a DBC score in the clinical range. No adult (>30 years) had incontinence or a critical DBC score. Children and adolescents with NE had significantly higher scores in the DBC total score as well in the "self-absorbed" and "social relating" subscales than continent children and adolescents, whereas no significant difference was found between children and adolescents with DUI compared with the continent group. Conclusions A significant proportion of children with NS are affected by incontinence. Incontinence is a relevant problem in children and adolescents with NS, but does not persist into adulthood. In particular, psychological problems are present in children and adolescents with NE. Screening for both incontinence and psychological symptoms are recommended in children with NS. As most of the children with NS have average intelligence or a mild ID, they can be treated effectively with standard methods