Design and development of microformulations for rapid release of small molecules and oligonucleotides.

A systemic delivery of therapeutics frequently results in sub-optimal exposure of the targeted locus and undesired side effects. To address these challenges, a platform for local delivery of diverse therapeutics by remotely controlled magnetic micro-robots was introduced. The approach involves micro-formulation of active molecules using hydrogels that exhibit wide range of loading capabilities and predictable release kinetics. This work introduces two specific hydrogels based on thiol-maleimide and PEG-PLA-diacrylate chemistries that afford high, reliable and reproducible loading and release of several model molecules including doxorubicin, 25-mer poly-dT oligonucleotide and a 5.4 kBp GFP DNA plasmid. The described formulations are suitable for micro-dosing using both conventional or remote delivery devices.

Cephalic vein transposition in head-and-neck reconstruction.

The advent of free flaps has made it possible to undertake increasingly complex reconstructive surgeries. Many of the patients have already undergone extensive prior surgery, primary free flap reconstruction and/or cervical irradiation. These treatments strongly impact anatomy and tissue quality. The reconstructive surgeon may be faced with a situation where the choice of recipient vessels is limited; in 7% of cases, no cervical vessels are available at all. For venous anastomosis, branches of the internal and external jugular vein are preferentially used, but may have been ligated or be unusable. Venous congestion is one of the most common causes of failure in these situations. The cephalic vein has been described as an alternative for second anastomosis in first line, but is rarely used for early free-flap salvage. Based on a case study, the technique of cephalic vein transposition is illustrated for early salvage of a double free flap for head-and-neck reconstruction. This technique is simple, reliable and rapid. It should be part of the armamentarium of the head and neck reconstructive surgeon.

The venous return simulator: comparison of simulated with measured ambulatory venous pressure in normal subjects and in venous valve incompetence.

BACKGROUND: To compare results of numerical simulation of lower limb venous return with those of in vivo measurements, in normal subjects, and those with venous incompetence. PATIENTS AND METHODS: the venous return simulator (VRS) is a mathematical model which takes into account architecture, dimensions, and compliance of the venous network, blood viscosity, valve function, and external pressures (muscular contraction, compression stockings). Using the laws of hydrodynamics, it provides calibres, pressures and flows throughout the network. Ambulatory venous pressure (AVP) computed for some theoretical examples of superficial and /or deep venous incompetence has been compared to in vivo values reported in literature. RESULTS: In a normal subject, computed AVP was 33 mmHg during walking and 30 mmHg with tiptoe exercise; the range of conventionally measured AVP is 20.6 - 27.9 mmHg during walking, and 29 - 32.5 mmHg during tiptoe exercise; In the case of great saphenous vein (GSV) incompetence, computed AVP was 34 or 57 mmHg, according to whether the distal GSV was competent or not. The range of AVP measured in superficial venous insufficiency is 27.6 - 61 mmHg, all but one of the published values lie between the low computed value corresponding to a short reflux and the high computed value due to a long distance reflux. AVP computed in two cases of deep venous incompetence was 44 and 71 mmHg, according to the extent of devalvulation, as compared with the 60 mmHg reported in one clinical study In patients with extensive combined incompetence, computed AVP was 75 mmHg, whilst the range of conventionally measured values was between 62 and 84 mmHg. CONCLUSIONS: the good agreement between computed and measured AVP in different cases of valve incompetence indicates that the VRS is quite a realistic model, with the potential to simulate the results of surgery or compression therapy.

The venous return simulator: an effective tool for investigating the effects of external compression on the venous hemodynamics--first results after thigh compression.

BACKGROUND: To present a virtual model, the venous return simulator (VRS), designed to compute venous hemodynamic variations when compression is applied to the leg. METHODS: The VRS defines a numerical network of the lower extremity and computes the dynamic variables (flow rate, venous diameter and internal pressure) for a defined external pressure. The VRS was based on physiological data from the literature and clinical studies on healthy subjects. Clinical correlations were required to confirm its validity; for this purpose, we carried out experiments simulating the conditions of a clinical trial, in which the diameter of superficial and deep veins was measured while increasing pressures (20, 40 and 60 mmHg.) were applied to the thighs of patients enduring deep valvular insufficiency and venous ulcers. The diameters and flow rates calculated using our VRS model were compared with the experimental data obtained at the same thigh compression levels. RESULTS: The numerical results of VRS are in good agreement with the clinical data obtained by Duplex, (R2 = 0.96). In accordance with the in vivo measurement the computed results show that only a pressure greater than 40 mmHg is able to reduce the venous diameter at thigh-level, both in the great saphenous vein and in the femoral vein. CONCLUSION: The venous return simulator computes lower limb hemodynamic parameters under static conditions. The good correlation existing between the VRS and the data obtained in a previous clinical study shows that this numerical approach could provide a useful means of predicting the hemodynamic consequences of compression therapy.

Xenon-131 surface sensitive imaging of aerogels in liquid xenon near the critical point.

In recent years, optically pumped xenon-129 has received a great deal of attention as a contrast agent in gas-phase imaging. This report is about the other NMR active xenon isotope (i.e., xenon-131, S = 32) which exhibits distinctive features for imaging applications in material sciences that are not obtainable from xenon-129 (S = (1/2)). The spin dynamics of xenon-131 in gas and liquid phases is largely determined by quadrupolar interactions which depend strongly on the surface of the surrounding materials. This leads to a surface dependent dispersion of relaxation rates, which can be substantial for this isotope. The dephasing of the coherence due to quadrupolar interactions may be used to yield surface specific contrast for imaging. Although optical pumping is not practical for this isotope because of its fast quadrupolar relaxation, a high spin density of liquid xenon close to the critical point (289 K) overcomes the sensitivity problems of xenon-131. We report the first xenon-131 magnetic resonance images and have tested this technique on various meso-porous aerogels as host structures. Aerogels of different densities and changing levels of hydration can clearly be distinguished from the images obtained.

Quenched molecular reorientation and angular velocity in nanopores.

A theoretical treatment shows how the orientational dependent and spin rotation relaxation rates of a confined nonpolar liquid depend on the average pore size. Experimental nuclear relaxation data on carbon disulfide and cyclohexane in a set of calibrated porous glasses support the theory.

A digital model for the venous junctions.

The venous network in the lower limbs is composed of a considerable number of confluent junctions. Each of these singularities introduces some blood flow disturbances. Each physiological junction is unique, in terms of its geometry as well as the blood flow rate. In order to account for this great variability, we developed a numerical model based on the use of the N3S code (a software package for solving Navier-Stokes equations). To test the validity of the model, one of the numerical simulations is compared with the data obtained in the corresponding experimental configuration. The velocity measurements were carried out with an ultrasonic pulsed Doppler velocimeter. We also measured pressure differences using differential sensors. The numerical computations were then used to obtain the values of the flow variables at any point, with various geometrical and flow configurations. As far as the velocity field is concerned, a very marked three-dimensional pattern with swirls was observed. The pressure evolution was also strongly disturbed, with a non-linear decrease. All these data indicate that confluence effects cannot be neglected when evaluating pressure decreases. With a tool of this kind, it is possible to accurately predict the disturbances associated with any geometrical configuration or any flow rate.