Hyperthermic potentiation of cisplatin by magnetic nanoparticle heaters is correlated with an increase in cell membrane fluidity.

Magnetic fluid hyperthermia as a cancer treatment method is an attractive alternative to other forms of hyperthermia. It is based on the heat released by magnetic nanoparticles subjected to an alternating magnetic field. Recent studies have shown that magnetic fluid hyperthermia-treated cells respond significantly better to chemotherapeutic treatment compared with cells treated with hot water hyperthermia under the same temperature conditions. We hypothesized that this synergistic effect is due to an additional stress on the cellular membrane, independent of the thermal heat dose effect that is induced by nanoparticles exposed to an alternating magnetic field. This would result in an increase in Cis-diammine-dichloroplatinum (II) (cDDP, cisplatin) uptake via passive transport. To test this hypothesis, we exposed cDDP-treated cells to extracellular copper in order to hinder the human cell copper transporter (hCTR1)-mediated active transport of cDDP. This, in turn, can increase the passive transport of the drug through the cell membrane. Our results did not show statistically significant differences in surviving fractions for cells treated concomitantly with magnetic fluid hyperthermia and cDDP, in the presence or absence of copper. Nonetheless, significant copper-dependent variations in cell survival were observed for samples treated with combined cDDP and hot water hyperthermia. These results correlated with platinum uptake studies, which showed that cells treated with magnetic fluid hyperthermia had higher platinum uptake than cells treated with hot water hyperthermia. Changes in membrane fluidity were tested through fluorescence anisotropy measurements using trimethylamine-diphenylhexatriene. Additional uptake studies were conducted with acridine orange and measured by flow cytometry. These studies indicated that magnetic fluid hyperthermia significantly increases cell membrane fluidity relative to hot water hyperthermia and untreated cells, and hence this could be a factor contributing to the increase of cDDP uptake in magnetic fluid hyperthermia-treated cells. Overall, our data provide convincing evidence that cell membrane permeability induced by magnetic fluid hyperthermia is significantly greater than that induced by hot water hyperthermia under similar temperature conditions, and is at least one of the mechanisms responsible for potentiation of cDDP by magnetic fluid hyperthermia in Caco-2 cells.

Enhanced reduction in cell viability by hyperthermia induced by magnetic nanoparticles.

Colloidal suspensions of iron oxide magnetic nanoparticles are known to dissipate energy when exposed to an oscillating magnetic field. Such energy dissipation can be employed to locally raise temperature inside a tumor between 41°C and 45°C (hyperthermia) to promote cell death, a treatment known as magnetic fluid hyperthermia (MFH). This work seeks to quantify differences between MFH and hot-water hyperthermia (HWH) in terms of reduction in cell viability using two cancer cell culture models, Caco-2 (human epithelial colorectal adenocarcinoma) and MCF-7 (human breast cancer). Magnetite nanoparticles were synthesized via the co-precipitation method and functionalized with adsorbed carboxymethyl dextran. Cytotoxicity studies indicated that in the absence of an oscillating magnetic field, cell viability was not affected at concentrations of up to 0.6 mg iron oxide/mL. MFH resulted in a significant decrease in cell viability when exposed to a magnetic field for 120 minutes and allowed to rest for 48 hours, compared with similar field applications, but with shorter resting time. The results presented here suggest that MFH most likely induces apoptosis in both cell types. When compared with HWH, MFH produced a significant reduction in cell viability, and these effects appear to be cell-type related.

Estimation of the differential pressure at renal artery stenoses.

Atherosclerotic disease of the renal artery can lead to reduction in arterial caliber and ultimately to conditions including renovascular hypertension. Renal artery stenosis is conventionally assessed, using angiography, according to the severity of the stenosis. However, the severity of a stenosis is not a reliable indicator of functional significance, or associated differential pressure, of a stenosis. A methodology is proposed for estimation of the renal artery differential pressure (RADP) from MR imaging. Realistic computational fluid dynamics (CFD) models are constructed from MR angiography (MRA) and phase-contrast (PC) MR. The CFD model is constructed in a semiautomated manner from the MR images using the Isosurface Deformable Model (IDM) for surface reconstruction and a Marching Front algorithm for construction of the volumetric CFD mesh. Validation of RADP estimation was performed in a realistic physical flow-through model. Under steady flow, the CFD estimate of the differential pressure across a stenosis in the physical flow-through model differed by an average of 5.5 mmHg from transducer measurements of the pressure differential, for differential pressures less than 60 mmHg. These results demonstrate that accurate estimates of differential pressure at stenoses may be possible based only on structural and flow images.

Blood flow modeling in carotid arteries with computational fluid dynamics and MR imaging.

RATIONALE AND OBJECTIVES: The authors' goal was to develop a noninvasive method for detailed assessment of blood flow patterns from direct in vivo measurements of vessel anatomy and flow rates. MATERIALS AND METHODS: The authors developed a method to construct realistic patient-specific finite element models of blood flow in carotid arteries. Anatomic models are reconstructed from contrast material-enhanced magnetic resonance (MR) angiographic images with a tubular deformable model along each arterial branch. A surface-merging algorithm is used to create a watertight model of the carotid bifurcation for subsequent finite element grid generation, and a fully implicit scheme is used to solve the incompressible Navier-Stokes equations on unstructured grids. Physiologic boundary conditions are derived from cine phase-contrast MR flow velocity measurements at two locations below and above the bifurcation. Vessel wall compliance is incorporated by means of fluid-solid interaction algorithms. RESULTS: The method was tested on imaging data from a healthy subject and a patient with mild stenosis. Finite element grids were successfully generated, and pulsatile blood flow calculations were performed. Computed and measured velocity profiles show good agreement. Flow patterns and wall shear stress distributions were visualized. CONCLUSIONS: Patient-specific computational fluid dynamics modeling based on MR images can be performed robustly and efficiently. Preliminary validation studies in a physical flow-through model suggest that the model is accurate. This method can be used to characterize blood flow patterns in healthy and diseased arteries and may eventually help physicians to supplement imaging-based diagnosis and predict and evaluate the outcome of interventional procedures.

Expansor hidráulico para cavidad orbitaria anoftálmica retraída / Hidraulic expander for contracted anophthalmic sockets

Se presenta el expansor hidráulico (globo lleno con agua), un sencillo y económico método que permitiría en forma incruenta expandir cavidades anoftámicas retraídas, pudiendo ser útil como único tratamiento o ser complementado con la cirugía para corregir alteraciones palpebrales y aumento de volumen en órbitas deficitarias. Se discute el hecho si además pudiese ser de utilidad en la expansión de partes óseas en el anoftalmo congénito