In vivo transfer and expression of a human epidermal growth factor gene accelerates wound repair.

This report details the transfer of a human epidermal growth factor (hEGF) expression plasmid to porcine partial-thickness wound keratinocytes by particle-mediated DNA transfer (Accell). After gene transfer an external sealed fluid-filled wound chamber was used to protect the wound, provide containment of the exogenous DNA and expressed peptide, and permit sampling of the wound fluid. Analysis of wound fluid for hEGF and total protein, an indicator of reformation of the epithelial barrier, showed that wounds bombarded with the hEGF plasmid exhibited a 190-fold increase in EGF concentration and healed 20% (2.1 days) earlier than the controls. EGF concentrations in wound fluid persisted over the entire 10-day monitored period, decreasing from 200 pg/ml to 25 pg/ml over the first 5 days. Polymerase chain reaction results showed that plasmid DNA was present in the wound for at least 30 days. These findings demonstrate the possible utility of in vivo gene transfer to enhance epidermal repair.     

„Breast implant illness“ – Fakt oder Fiktion?

Journal für Ästhetische Chirurgie - Brustvergrößerungen mit Implantaten gehören zu den häufigsten ästhetisch chirurgischen Eingriffen. Trotz jahrzehntelanger...     

Gene therapy perspectives in modulation of wound healing

A variety of reasons can afflict wound healing. Current research is focussed on the acceleration of wound healing by stimulating molecular processes. Gene therapy may offer completely new ways to treat chronic wounds. Possible advantages of gene therapeutic modulation of wound healing might be a long term efficiency, systemic or local regulation of gene expression and low side-effects. Current goals comprise the improvement of transfection efficiency and specificity. In vivo applications are therefore focussed on optimized inducible or even cell-type specific promotors, as well as on improved local application techniques. Studies from our laboratory demonstrate the possibility to combine modern cell culture techniques with different types of gene transfer. This enables the simultaneous grafting of manipulated cells to the wound with the continuous delivery of specific proteins of interest. Experimentally, this lead to accelerated closure of partial and full thickness animal wounds. Clinically, gene therapy for the treatment of chronic wounds seems to be a realistic goal within the next years and might be applicable for a variety of novel indications.     

Assessing Generalization of the Picture Exchange Communication System in Children with Autism

Since its introduction to the field, a growing body of research on the Picture Exchange Communication System (PECS) has demonstrated its efficacy for children with autism in research settings. However, knowledge of PECS generalization remains limited and mixed. The present study explored a train and probe technique of assessing generalization after each phase of PECS training. Four children with autism were taught PECS in treatment rooms with a therapist at their behavioral treatment program. Generalization was assessed in a playroom with a therapist, at home with a therapist and parent, and in the community with a stranger. Results indicated that all four participants generalized PECS use across settings and people and maintained PECS use at follow-up. Findings provide support for the utility of a train and probe technique to assess generalization when using PECS with children with autism.     

Der Resektionsrand und seine Beurteilung

In recent years there has been an intensive discussion about how to define a negative surgical resection margin. Despite the impact of radiation and systemic therapy a positive margin in breast surgery is associated with an increased risk of local recurrence. Thus, a positive margin confirmed by the pathologist results in further surgery that is troublesome for the patient in several ways and can also delay the initiation of adjuvant treatment. Therefore, the field of intraoperative margin assessment was intensively investigated and methods and technologies have been developed to support the breast surgeon in the operating theater. Some of these developments, such as frozen sections, touch imprint cytology, intraoperative ultrasound and radiofrequency spectroscopy are now established in the clinical routine. Others, such as near-infrared optical imaging, X-ray diffraction, high-frequency ultrasound and micro-computed tomography (CT) are still in the experimental stage. This article illustrates the current status of defining a negative surgical margin and gives an overview of the various and innovative technologies for intraoperative margin assessment.     

Significance of IGFBP-4 in the Development of Fetal Growth Restriction

Background: Fetal growth restriction (FGR) is a leading cause of perinatal mortality and morbidity. Animal studies suggest dysregulation of IGF-binding protein (IGFBP)-4 is significant in the development of FGR, although human data are lacking. We postulated that IGFBP-4 is expressed at the maternal fetal interface and plays a role in regulating IGF bioavailability. Thus, maternal serum levels of IGFBP-4 may be associated with complications of abnormal placental growth and development including FGR. Methods: Circulating levels of IGFBP-4 and its protease, pregnancy-associated plasma protein-A (PAPP-A), were examined in healthy pregnancies. Their expression in villi and bed as possible sources of the circulating products were examined by immunohistochemistry. From the large Ottawa and Kingston (OaK) Birth Cohort, a nested case-control study was conducted to examine circulating levels of IGBP-4, PAPP-A, IGF-I, and IGF-II by Western blot in early gestation in 36 women who went on to develop FGR and 36 controls having normal-weight babies. Results: IGFBP-4 was elevated in early pregnancy compared with nonpregnant women and women in later pregnancy, consistent with the presence of abundant extravillous trophoblasts and decidual cells that highly expressed IGFBP-4. High expression of PAPP-A was observed in extravillous trophoblasts and decidual cells in early pregnancy but hardly detectable in the circulation at this time, suggesting maternal circulating PAPP-A originates more likely from syncytiotrophoblasts. Increased IGFBP-4 in the maternal circulation in early pregnancy was associated with the development of FGR [0.48 (0.28-0.74) in control vs. 1.22 (0.66-1.65) in FGR; odds ratio = 22 (95% confidence interval = 2.7-181)]. No difference was observed in circulating PAPP-A, IGF-I and IGF-II in the FGR vs. control group. Conclusion: Our findings support the role of IGFBP-4 in regulating IGF bioavailability and provide new clues for the prevention and treatment of FGR, raising the possibility of clinical use of IGFBP-4 as an early biomarker for this condition.     

Dental composite materials containing carolacton inhibit biofilm growth of Streptococcus mutans

Objective

Caries adjacent to restorations is one of the main causes for restoration replacement. Antimicrobial substances incorporated into dental materials would potentially be able to reduce secondary caries initiation and progression. This study investigated biofilm growth of Streptococcus mutans UA159 on the surface of composite materials containing the biomolecule carolacton compared to materials containing chlorhexidine (CHX) and triclosan.

Methods

Biofilm inhibition was investigated by counting colony forming units (CFU), viability staining (Life/Dead), and real-time quantitative PCR.

Results

First, the antimicrobial substances were added to the cultivation medium at 2.5 μg/ml (0.0002%) and 0.25 μg/ml (0.00002%). CHX eliminated bacterial growth and biofilm formation completely. Triclosan was effective at 2.5 μg/ml, but at 0.25 μg/ml biofilm mass and viability were unchanged, yet the number of CFU increased due to disruption of cell chains and biofilm aggregates. Carolacton had a limited effect on biofilm growth and mass, but reduced viability significantly. When incorporated into composite materials carolacton (25 μg/ml resp. 0.002%, w/w) had no adverse effect on physical/mechanical properties and retained its biofilm inhibiting effect. Life/Dead staining revealed a reduction of biofilm viability of up to 64%. CFUs were reduced by 98% and qPCR demonstrated a mean inhibition of 87%. In contrast, materials containing CHX or triclosan showed an insignificant effect on biofilm formation, even at a 100fold increased concentration (0.2%). The anti-biofilm activity of composite material containing carolacton was stable over a period of 42 days.

Significance

Carolacton incorporated into dental filling material has a strong biofilm-inhibiting effect on S. mutans and is therefore potentially able to prevent secondary caries formation.