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.     

Amphetamine-Induced Dopamine Release and Neurocognitive Function in Treatment-Naive Adults with ADHD

Converging evidence from clinical, preclinical, neuroimaging, and genetic research implicates dopamine neurotransmission in the pathophysiology of attention deficit hyperactivity disorder (ADHD). The in vivo neuroreceptor imaging evidence also suggests alterations in the dopamine system in ADHD; however, the nature and behavioral significance of those have not yet been established. Here, we investigated striatal dopaminergic function in ADHD using [¹¹C]raclopride PET with a d-amphetamine challenge. We also examined the relationship of striatal dopamine responses to ADHD symptoms and neurocognitive function. A total of 15 treatment-free, noncomorbid adult males with ADHD (age: 29.87±8.65) and 18 healthy male controls (age: 25.44±6.77) underwent two PET scans: one following a lactose placebo and the other following d-amphetamine (0.3 mg/kg, p.o.), administered double blind and in random order counterbalanced across groups. In a separate session without a drug, participants performed a battery of neurocognitive tests. Relative to the healthy controls, the ADHD patients, as a group, showed greater d-amphetamine-induced decreases in striatal [¹¹C]raclopride binding and performed more poorly on measures of response inhibition. Across groups, a greater magnitude of d-amphetamine-induced change in [¹¹C]raclopride binding potential was associated with poorer performance on measures of response inhibition and ADHD symptoms. Our findings suggest an augmented striatal dopaminergic response in treatment-naive ADHD. Though in contrast to results of a previous study, this finding appears consistent with a model proposing exaggerated phasic dopamine release in ADHD. A susceptibility to increased phasic dopamine responsivity may contribute to such characteristics of ADHD as poor inhibition and impulsivity.     

Breastfeeding and complementary feeding as a public health intervention for child survival in India

The relevance of breastfeeding and complementary feeding as proven child survival interventions, is well documented by the scientific research. These two preventive interventions can save as many as 19% of all child deaths. However, despite the volume of evidence favouring mainstreaming of these interventions, many countries, including India are yet to achieve universal appropriate infant and young child feeding practices. This article attempts to explore the evidenced based role of these interventions in the crusade to save children, and looks into the present scenario of infant and young child feeding in India, along with a possible road map to achieve high rates of early and exclusive breastfeeding and appropriate complementary feeding in the country.     

Improved anticancer delivery of paclitaxel by albumin surface modification of PLGA nanoparticles

Background

Nanoparticles (NPs) play an important role in anticancer delivery systems. Surface modified NPs with hydrophilic polymers such as human serum albumin (HSA) have long half-life in the blood circulation system.

Methods

The method of modified nanoprecipitation was utilized for encapsulation of paclitaxel (PTX) in poly (lactic-co-glycolic acid) (PLGA). Para-maleimide benzoic hydrazide was conjugated to PLGA for the surface modifications of PLGA NPs, and then HSA was attached on the surface of prepared NPs by maleimide attachment to thiol groups (cysteines) of albumin. The application of HSA provides for the longer blood circulation of stealth NPs due to their escape from reticuloendothelial system (RES). Then the physicochemical properties of NPs like surface morphology, size, zeta potential, and in-vitro drug release were analyzed.

Results

The particle size of NPs ranged from 170 to 190 nm and increased about 20–30 nm after HSA conjugation. The zeta potential was about -6 mV and it decreased further after HSA conjugation. The HSA conjugation in prepared NPs was proved by Fourier transform infrared (FT-IR) spectroscopy, faster degradation of HSA in Differential scanning calorimetry (DSC) characterization, and other evidences such as the increasing in size and the decreasing in zeta potential. The PTX released in a biphasic mode for all colloidal suspensions. A sustained release profile for approximately 33 days was detected after a burst effect of the loaded drug. The in vitro cytotoxicity evaluation also indicated that the HSA NPs are more cytotoxic than plain NPs.

Conclusions

HSA decoration of PLGA NPs may be a suitable method for longer blood circulation of NPs.