Inhibition of stromal cell-derived factor-1α further impairs diabetic wound healing

ObjectiveImpaired diabetic wound healing is associated with abnormal stromal cell-derived factor (SDF)-1α production, decreased angiogenesis, and chronic inflammation. Lentiviral-mediated overexpression of SDF-1α can correct the impairments in angiogenesis and healing in diabetic wounds. We hypothesized that SDF-1α is a critical component of the normal wound-healing response and that inhibition of SDF-1α would further delay the wound-healing process.MethodsdB/Db diabetic mice and Db/+ nondiabetic mice were wounded with an 8-mm punch biopsy and the wounds treated with a lentiviral vector containing either the green fluorescent protein (GFP) or SDF-1α inhibitor transgene. The inhibitor transgene is a mutant form of SDF-1α that binds, but does not activate, the CXCR4 receptor. Computerized planimetry was used to measure wound size daily. Wounds were analyzed at 3 and 7 days by histology and for production of inflammatory markers using real-time polymerase chain reaction. The effect of the SDF-1α inhibitor on cellular migration was also assessed.ResultsInhibition of SDF-1α resulted in a significant decrease in the rate of diabetic wound healing, (3.8 vs 6.5 cm2/day in GFP-treated wounds; P = .04), and also impaired the early phase of nondiabetic wound healing. SDF-1α inhibition resulted in fewer small-caliber vessels, less granulation tissue formation, and increased proinflammatory gene expression of interleukin-6 and macrophage inflammatory protein-2 in the diabetic wounds.ConclusionsThe relative level of SDF-1α in the wound plays a key role in the wound-healing response. Alterations in the wound level of SDF-1α, as seen in diabetes or by SDF-1α inhibition, impair healing by decreasing cellular migration and angiogenesis, leading to increased production of inflammatory cytokines and inflammation. Inhibition of SDF-1α further impairs diabetic wound healing.Clinical RelevanceDiabetes results in a significant impairment in wound healing, leading to significant morbidity and health care expenditures. The pathophysiology that underlies this process is multifactorial, including abnormal growth factor production, cellular migration, and cellular function. Stromal cell-derived factor (SDF)-1α is a key chemokine involved in the wound-healing process and is involved in cellular recruitment and angiogenesis. SDF-1α is decreased in diabetic individuals. This study showed that inhibition of SDF-1α results in an even more dramatic delay in the diabetic wound-healing process and even results in a delay in the early phases of wound healing in normal mice, further supporting its role in wound healing. Inhibition of this chemokine promotes greater inflammatory cytokine production, inflammatory cell migration, and less vasculogenesis after dermal wounding. This study identifies SDF-1α as an essential component of normal wound healing and provides a potential therapeutic target to improve the diabetic wound-healing impairment

Emulsion Membranes Iodine Separation I. Preparation of organic phase membrane emulsion / receiving aqueous solution

One of the major obstacles in membranes achievemen

Safety of AAV Factor IX Peripheral Transvenular Gene Delivery to Muscle in Hemophilia B Dogs

Muscle represents an attractive target tissue for adeno-associated virus (AAV) vector–mediated gene transfer for hemophilia B (HB). Experience with direct intramuscular (i.m.) administration of AAV vectors in humans showed that the approach is safe but fails to achieve therapeutic efficacy. Here, we present a careful evaluation of the safety profile (vector, transgene, and administration procedure) of peripheral transvenular administration of AAV-canine factor IX (cFIX) vectors to the muscle of HB dogs. Vector administration resulted in sustained therapeutic levels of cFIX expression. Although all animals developed a robust antibody response to the AAV capsid, no T-cell responses to the capsid antigen were detected by interferon (IFN)-γ enzyme-linked immunosorbent spot (ELISpot). Interleukin (IL)-10 ELISpot screening of lymphocytes showed reactivity to cFIX-derived peptides, and restimulation of T cells in vitro in the presence of the identified cFIX epitopes resulted in the expansion of CD4+FoxP3+IL-10+ T-cells. Vector administration was not associated with systemic inflammation, and vector spread to nontarget tissues was minimal. At the local level, limited levels of cell infiltrates were detected when the vector was administered intravascularly. In summary, this study in a large animal model of HB demonstrates that therapeutic levels of gene transfer can be safely achieved using a novel route of intravascular gene transfer to muscle

The influence of ultrasounds on the process of uranium desorption

In the present paper, we have studied the intensification of the desorption process of the complex anions of uranium U(VI), from ion exchange resins under the action of the ultrasonic field. The dynamics of uranium desorption from the anionic resins Purolite A600U/3472 and PM 611 was analyzed, both in standard conditions and with ultrasounds. The use of ultrasounds leads to the substantial growth of desorption kinetics and of the uranium recovery degree. The tests for stability of the resin grains size, mechanical resistance and the capacity of loading with uranium, after the repeated action of the ultrasounds field, emphasized the physical-chemical stability of resins used in the experiment (loading capacity of untreated resin 30.36 mgU/g resin and treated in continuous ultrasonic field 30.85 mgU/g resin)

The influence of ultrasounds on the process of uranium desorption

In the present paper, we have studied the intensification of the desorption process of the complex anions of uranium U(VI), from ion exchange resins under the action of the ultrasonic field. The dynamics of uranium desorption from the anionic resins Purolite A600U/3472 and PM 611 was analyzed, both in standard conditions and with ultrasounds. The use of ultrasounds leads to the substantial growth of desorption kinetics and of the uranium recovery degree. The tests for stability of the resin grains size, mechanical resistance and the capacity of loading with uranium, after the repeated action of the ultrasounds field, emphasized the physical-chemical stability of resins used in the experiment (loading capacity of untreated resin 30.36 mgU/g resin and treated in continuous ultrasonic field 30.85 mgU/g resin)

Protection Devices Testing based on Power-Hardware-in-the-Loop Simulation

International audienc

Hardware-in-the-loop simulation applied to protection devices testing

International audienceCircuit breakers are ubiquitous elements used for ensuring safe operation of low-voltage power systems. Nowadays the loads supplied by the power systems migrate towards exhibiting significant strong nonlinear behavior accompanied by inrush currents or high-order harmonics that can cause a false tripping of circuit breakers. It is thus necessary to study the interaction between these new loads and the protection devices in order to fully assess their compatibility. Following this context, this paper deals with a new test rig dedicated to protection switching devices, which is based on the hardware-in-the-loop real-time simulation concept. The proposed approach is focused on replicating the tripping conditions of a real circuit breaker coupled to a power system emulated by means of a real-time simulator. The software part of this simulator adds flexibility to the test rig as the circuit configurations and the operating scenarios may conveniently be adapted at lowest cost. The control of the interface between the software simulator and the hardware under test, as well as the closed-loop stability issues, has been thoroughly approached. Experiments carried out on this test rig show the effectiveness of this new test prototyping concept in characterizing real circuit breakers behavior when they protect lighting circuits