Biomedical subjects

P D Mourad

Publications and source records attributed to P D Mourad.

8 recordsLinked to original sources

PubMed2001

Self-assembled molecular structures as ultrasonically-responsive barrier membranes for pulsatile drug delivery.

Noninvasive ultrasound has been shown to increase the release rate on demand from drug delivery systems; however, such systems generally suffer from background drug leaching. To address this issue, a drug-containing polymeric monolith coated with a novel ultrasound-responsive coating was developed. A self-assembled molecular structure coating based on relatively impermeable, ordered methylene chains forms an ultrasound-activated on-off switch in controlling drug release on demand, while keeping the drug inside the polymer carrier in the absence of ultrasound. The orderly structure and molecular orientation of these C12 n-alkyl methylene chains on polymeric surfaces resemble self-assembled monolayers on gold. Their preparation and characterization have been published recently (Kwok et al. [Biomacromolecules 2000;1(1):139-148]). Ultrasound release studies showed that a copolymer of 2-hydroxyethyl methacrylate and ethylene glycol dimethacrylate (MW 400) coated with such an ultrasound-responsive membrane maintained sufficient insulin for multiple insulin delivery, compared with a substantial burst release during the first 2 h from uncoated samples. With appropriate surface coating coverage, the background leach rate can be precisely controlled. The biological activity of the insulin releasate was tested by assessing its ability to regulate [C14]-deoxyglucose uptake in 3T3-L1 adipocyte cells in a controlled cell culture environment. Uptake triggered by released insulin was comparable to that of the positive insulin control. The data demonstrate that the released insulin remains active even after the insulin had been exposed to matrix synthesis and the methylene chain coating process.

Adipocytes↗

PubMed2001

Activation, aggregation and adhesion of platelets exposed to high-intensity focused ultrasound.

Using platelet-rich plasma, we investigated the effect of 1.1-MHz continuous wave high-intensity focused ultrasound (HIFU) on platelet activation, aggregation and adhesion to a collagen-coated surface. Platelets were exposed for durations of 10-500 s at spatial average intensities of up to 4860 W/cm(2). To avoid heating effects, the average temperature in the HIFU tank was maintained at 33.8 +/- 4.0 degrees C during platelet experiments. Flow cytometry, laser aggregometry, environmental scanning electron microscopy and passive cavitation detection were used to observe and to quantify platelet activation, aggregation, adhesion to a collagen-coated surface and associated cavitation. It was determined that HIFU can activate platelets, stimulate them to aggregate and promote their adherence to a collagen-coated surface. In principle, HIFU can stimulate primary, or platelet-related, hemostasis. Cavitation was monitored by a passive cavitation detector during aggregation trials and was quantified to provide a relative measure of the amount of cavitation that occurred in each aggregation trial. Regression analysis shows a weak correlation (r(2) = 0.11) between aggregation and ultrasound intensity, but a substantial correlation (r(2) = 0.76) between aggregation and cavitation occurrence.

Flow Cytometry↗

PubMed2001

Ultrasound accelerates functional recovery after peripheral nerve damage.

OBJECTIVE: Axonal injury in the peripheral nervous system is common, and often it is associated with severe long-term personal and societal costs. The objective of this study is to use an animal model to demonstrate that transcutaneous ultrasound can accelerate recovery from an axonotmetic injury. METHODS: The sciatic nerve of adult male Lewis rats was crushed in the right midthigh to cause complete distal degeneration of axons yet maintain continuity of the nerve. Beginning 3 days after surgery, various transcutaneous ultrasound treatments or sham treatments were applied 3 days per week for 30 days to the crush site of rats that were randomly assigned to two groups. In the preliminary experiments, there were three animals in each ultrasound group and two control animals. In the final experiment, there were 22 animals in the ultrasound group and 20 animals in the control group. Recovery was assessed by use of a toe spread assay to quantify a return to normal foot function in the injured leg. Equipment included a hand-held transducer that emitted continuous-wave ultrasound. The most successful ultrasound protocol had a spatial peak, time-averaged intensity of 0.25 W/cm2 operated at 2.25 MHz for 1 minute per application. RESULTS: Rats subjected to the most successful ultrasound protocol showed a statistically significant acceleration of foot function recovery starting 14 days after injury versus 18 days for the control group. Full recovery by the ultrasound group occurred before full recovery by the control group. CONCLUSION: Transcutaneous ultrasound applied to an animal model of axonotmetic injury accelerated recovery. Future studies should focus on identification of the mechanism(s) by which ultrasound creates this effect, as a prelude to optimization of the protocol, demonstration of its safety, and its eventual application to humans.

Animals↗

PubMed2001

Thresholds for inertial cavitation in albunex suspensions under pulsed ultrasound conditions.

Stabilized microbubbles used as echo-contrast agents can be destroyed by ultrasonic irradiation. We have identified two pressure thresholds at which these microbubbles undergo inertial cavitation (here, defined as the collapse of gas bubbles followed by emission of an acoustic broadband noise). The first threshold (P1) corresponds to the pressure at which all the microbubbles in a cavitation field lose their property as an effective scatterer because of fragmentation or deflation. The second threshold (P2) is associated with the acoustic reactivation of the remnants of the contrast agents and is related to the onset of more violent inertial cavitation. P1 and P2 were measured as a function of the concentration of Albunex (Molecular Biosystems Inc., San Diego, CA) contrast agent, the number of transmitting acoustic cycles, and the pulse repetition frequency (PRF). The ultrasound frequency used was 1.1 MHz, and the peak negative acoustic pressures ranged from 0 to 8 MPa. Our results, measured in Isoton II (Coulter Diagnostics, Miami, FL) and whole blood solutions, showed that P1 increased with increasing Albunex concentration and decreased with increasing PRF, whereas P2 decreased with increasing Albunex concentration and was independent of the PRF. Both P1 and P2 decreased with increasing number of acoustic cycles N for N < 10 and were independent of the number of cycles for N > 10. Ultrasound images of Albunex acquired by a commercial scanner showed echo enhancement not only at pressure levels below P1 but also at levels above P2. The threshold P2 was achieved at ultrasound energies above the diagnostic level. Inertial cavitation produced at P2 was associated with a higher level of hemolysis compared with P1. The results of this investigation have potential significance for both diagnostic and therapeutic ultrasound applications.

Albumins↗

PubMed2001

Acceleration of recovery after injury to the peripheral nervous system using ultrasound and other therapeutic modalities.

Taken together, these studies show the promise of various therapeutic modalities for the noninvasive treatment of peripheral nerve injury. Further progress on these promising methods requires determining the biologic mechanisms responsible for the ability of these modalities to enhance peripheral nerve recovery. Necessary investigations include validation or refutation of the hypothesis that these therapies act on various aspects of the natural healing process. Examples include cellular and molecular processes involved in promoting Wallerian degeneration and the rate and specificity of axonal regeneration and remyelination and muscle reinnervation, processes that are distributed between the regenerating nerve itself, the pathway of the regenerating axon, and the target of the regenerating nerve. An increased understanding of the biologic mechanisms underlying the enhancement of peripheral nerve recovery after injury would lend greater insight into the cellular and molecular mechanisms involved in successful nerve regeneration and muscle reinnervation. This increased understanding may also result in clinically beneficial treatments for peripheral nerve disorders.

Animals↗

PubMed2000

Surface modification of polymers with self-assembled molecular structures: multitechnique surface characterization.

A simple, one-step procedure for generating ordered, crystalline methylene chains on polymeric surfaces via urethane linkages was developed. The reaction of dodecyl isocyanate with surface hydroxyl functional groups, catalyzed by dibutyltin dilaurate, formed a predominantly all-trans, crystalline structure on a cross-linked poly(2-hydroxyethyl methacrylate) (pHEMA) substrate. Allophanate side-branching reactions were not observed. Both X-ray photoelectron spectrocopy and time-of-flight secondary ion mass spectrometry show that the surface reaction reached saturation after 30 min at 60 degrees C. Unpolarized Fourier transform infrared-attenuated total reflection showed that, after 30 min, the stretching frequencies, vCH2,asym and vCH2,sym, decreased and approached 2920 and 2850 cm-1, indicative of a crystalline phase. The distance between two hydroxyl groups is roughly 4 A. A tilt angle of 33.5 degrees +/- 2.4 degrees was estimated by dichoric ratios measured in polarized ATR according to the two-phase and Harrick thin film approximations. The findings reported here are significant in that the possibilities for using structures similar to self-assembled monolayers (SAMs) are expanded beyond the rigid gold and silicon surfaces used through most of the literature. Thus, SAMs, biomimetics for ordered lipid cell wall structures, can be applied to real-world biomedical polymers to modify biological interactions. The terminal groups of the SAM-like structure can be further functionalized with biomolecules or antibodies to develop surface-based diagnostics, biosensors, or biomaterials.

Algorithms↗

PubMed1999

Effect of high-intensity focused ultrasound on whole blood with and without microbubble contrast agent.

Using human whole blood samples with and without contrast agent (CA), we evaluated the effect of exposures to focused, continuous wave (CW) 1.1-MHz ultrasound for durations of 10 ms to 1 s at spatial average intensities of 560 to 2360 W/cm2. Cavitation was monitored with a passive cavitation detector and hemolysis was determined with spectroscopy. In whole blood alone, no significant cavitation, heating or hemolysis was detected at any exposure condition. Conversely, cavitation and hemolysis, but not heating, were detected in whole blood with CA. A CA concentration as low as 0.28 microL CA per mL whole blood at an intensity of 2360 W/cm2 for 1 s resulted in measurable cavitation and a 6-fold increase in hemolysis compared to shams. Cavitation and hemolysis increased proportional to the concentration of CA and duration of exposure. In samples containing 4.2 microL CA per mL whole blood exposed for 1 s, a threshold was seen at 1750 W/cm2 where cavitation and hemolysis increased 10-fold compared to exposures at lower intensities. HIFU exposure of whole blood containing CA leads to significant hemolysis in vitro and may lead to clinically significant hemolysis in vivo.

Albumins↗

PubMed1999

A review and examination of ultrasound for lipoplasty.

Ultrasonic lipoplasty occurs through a complex and describable but currently unquantified series of processes. Ample opportunity exists for the creation of deleterious effects, such as burning tissue and destroying blood vessels and nerves; however, as reported by others, the skilled user seems able to avoid these problems. The possibility of free radical-induced cancer being caused by ultrasonic lipoplasty seems extremely unlikely to the authors. Still, the authors cannot categorically rule out the possibility of significant long-term, harmful, biologic effects caused by free-radical production. All the authors have been able to do is produce an extremely generous upper bound on hydrogen peroxide production and note the uphill climb that any free radical would have to surmount to do lasting damage. Also, users should ensure that no preexisting cancers are present in the fatty tissue or adjoining tissue. Finally, these and other issues, concerns, and hypotheses would all benefit from significant tests on appropriate animal models.

Animals↗