Low frequency and high intensity ultrasound in vascular surgery: theory, instrumentation and possibilities of clinical application

This paper presents a brief review of applications of ultrasound in modern surgery and results of original studies of the authors in the field of application of low frequency (24-36 kHz) high-intensity (up to 20 W/cm2) ultrasonic vibrations for disruption of thrombi and calcified atherosclerotic plaques in blood vessels. Application of non-rigid wire ultrasonic waveguides with length up to 980 mm and diameter of working tip down to 0.3 mm enables minimally invasive surgical intervention, since a waveguide can be introduced along curved segments of blood vessels through a small incision situated at substantial distance from occlusion. Ultrasonic angioplasty can be successfully applied in combination with administration of thrombolytic drugs. The paper also considers physical mechanisms of thrombus disruption under influence of ultrasonic vibrations, particularly, effects of cavitation and acoustic streaming. We described design of ultrasonic waveguides for endovascular surgery and their manufacturing technology based on plasma-electrolytic etching. Application of finite element method and transfer matrix approach for design and model of wire waveguides is considered. Description of clinical system for ultrasonic angioplasty with automated resonance tuning of a waveguide is also provided. In addition, we report results of clinical application of ultrasonic angioplasty in patients with occlusion of iliofemoral segment

Low frequency and high intensity ultrasound in vascular surgery: theory, instrumentation and possibilities of clinical application

This paper presents a brief review of applications of ultrasound in modern surgery and results of original studies of the authors in the field of application of low frequency (24-36 kHz) high-intensity (up to 20 W/cm2) ultrasonic vibrations for disruption of thrombi and calcified atherosclerotic plaques in blood vessels. Application of non-rigid wire ultrasonic waveguides with length up to 980 mm and diameter of working tip down to 0.3 mm enables minimally invasive surgical intervention, since a waveguide can be introduced along curved segments of blood vessels through a small incision situated at substantial distance from occlusion. Ultrasonic angioplasty can be successfully applied in combination with administration of thrombolytic drugs. The paper also considers physical mechanisms of thrombus disruption under influence of ultrasonic vibrations, particularly, effects of cavitation and acoustic streaming. We described design of ultrasonic waveguides for endovascular surgery and their manufacturing technology based on plasma-electrolytic etching. Application of finite element method and transfer matrix approach for design and model of wire waveguides is considered. Description of clinical system for ultrasonic angioplasty with automated resonance tuning of a waveguide is also provided. In addition, we report results of clinical application of ultrasonic angioplasty in patients with occlusion of iliofemoral segment

Discovery and characterization of novel selective inhibitors of carbonic anhydrase IX

Human carbonic anhydrase IX (CA IX) is highly expressed in tumor tissues, and its selective inhibition provides a potential target for the treatment of numerous cancers. Development of potent, highly selective inhibitors against this target remains an unmet need in anticancer therapeutics. A series of fluorinated benzenesulfonamides with substituents on the benzene ring was designed and synthesized. Several of these exhibited a highly potent and selective inhibition profile against CA IX. Three fluorine atoms significantly increased the affinity by withdrawing electrons and lowering the pKa of the benzenesulfonamide group. The bulky ortho substituents, such as cyclooctyl or even cyclododecyl groups, fit into the hydrophobic pocket in the active site of CA IX but not CA II, as shown by the compound's co-crystal structure with chimeric CA IX. The strongest inhibitor of recombinant human CA IX's catalytic domain in human cells achieved an affinity of 50 pM. However, the high affinity diminished the selectivity. The most selective compound for CA IX exhibited 10 nM affinity. The compound that showed the best balance between affinity and selectivity bound with 1 nM affinity. The inhibitors described in this work provide the basis for novel anticancer therapeutics targeting CA IX