Low-frequency Ultrasound Irradiation Research Articles

Investigation on The Effect of Low Frequency Ultrasound on The Crystallization of a Pharmaceutical Compound L+ Ascorbic Acid

One of the most crucial processes in the chemical processing industry is crystallization, which has the major challenge of producing solid products with the required purity and properties. The standard crystallization methods have various processing limitations; hence, research into alternative methods like ultrasonic-assisted crystallization has been at the forefront. The present work investigates the application of low-frequency ultrasound irradiation (40 kHz) for improving the cooling crystallization of ascorbic acid. The impact of ultrasonic irradiation on crystal size, shape, and induction time has been studied, and a comparison with the conventional method has been made. The standing time had a minor effect on particle size on average, while the initial temperature had a far more significant impact. Photographic analysis using image-analysis software indicated that when ultrasound was applied to the saturated solutions, the resulting crystals were smaller and more uniform in size and shape. The resultant crystal grows predominantly in a single direction, resembling thin prisms. The use of ultrasound was also shown to reduce the induction time significantly. This ultrasonic impact is stronger at lower initial temperatures. Indeed, the smallest induction time of 300 s was obtained for sonicated solutions at an initial temperature of 65°C and ultrasonic power of 250 w. When different levels of ultrasonic power dissipation were tested, it was established that the time required for the first nuclei to appear decreased as the power increased. There was, nevertheless, a marginal impact on average crystal size.

Enhancing glioma-specific drug delivery through self-assembly of macrophage membrane and targeted polymer assisted by low-frequency ultrasound irradiation

The blood-brain Barrier (BBB), combined with immune clearance, contributes to the low efficacy of drug delivery and suboptimal treatment outcomes in glioma. Here, we propose a novel approach that combines the self-assembly of mouse bone marrow-derived macrophage membrane with a targeted positive charge polymer (An-PEI), along with low-frequency ultrasound (LFU) irradiation, to achieve efficient and safe therapy for glioma. Our findings demonstrate the efficacy of a charge-induced self-assembly strategy, resulting in a stable co-delivery nanosystem with a high drug loading efficiency of 44.2 %. Moreover, this structure triggers a significant release of temozolomide in the acidic environment of the tumor microenvironment. Additionally, the macrophage membrane coating expresses Spyproteins, which increase the amount of An-BMP-TMZ that can evade the immune system by 40 %, while LFU irradiation treatment facilitates the opening of the BBB, allowing for enormously increased entry of An-BMP-TMZ (approximately 400 %) into the brain. Furthermore, after crossing the BBB, the Angiopep-2 peptide-modified An-BMP-TMZ exhibits the ability to selectively target glioma cells. These advantages result in an obvious tumor inhibition effect in animal experiments and significantly improve the survival of glioma-bearing mice. These results suggest that combining the macrophage membrane-coated drug delivery system with LFU irradiation offers a feasible approach for the accurate, efficient and safe treatment of brain disease.

Low-frequency ultrasound irradiation increases paclitaxel-induced sarcoma cells apoptosis and facilitates the transmembrane delivery of drugs.

Sarcoma is a malignant tumor derived from interstitial tissues and requires comprehensive treatment including chemotherapy. Paclitaxel (PTX) is an active agent against sarcoma, but its effect is not sufficiently acceptable and needs to be improved. Low-frequency ultrasound (LFU) has been documented to improve the efficacy of drugs by inducing reversible changes in membrane permeability; however, the effects of the combined use of LFU and PTX for sarcoma tumors remain unclear and warrant further investigation. We investigated the effects of 30kHz LFU treatment combined with PTX on sarcoma cells A-204 and HT-1080 by analyzing in vitro apoptosis and cell growth inhibition rates, and determined their antitumor effects by examining tumor weights with or without LFU in the S180 sarcoma xenograft model. Drug concentrations in the subcutaneous tumors were measured using high performance liquid chromatography (HPLC). LFU combined with PTX significantly induced cell apoptosis, and blocked the cell cycle of sarcoma cells in G2/M phase, and furthermore, inhibited the activation of JAK2/STAT3 signaling pathway. Meanwhile, LFU combined with PTX inhibited the expression of PD-L1 in vitro, suggesting the potential of enhanced antitumor immunity by this treatment. LFU combined with PTX significantly inhibited the growth of S180 tumors transplanted subcutaneously in Institute of Cancer Research (ICR) mice, and its enhanced effect may be associated with increased local concentrations of PTX in tumor tissues in vivo, with no significant adverse subsequences on body weight observed. We conclude that the combination of LFU and PTX has synergistic antitumor effects and is a candidate for subcutaneous treatment of sarcoma by further increasing the intracellular concentration of PTX.

Fast Scalable Synthetic Methodology to Prepare Nanoflower‐Shaped Bi/BiOClxBr1−x Heterojunction for Efficient Immobilized Photocatalytic Reactors under Visible Light Irradiation

AbstractThe metal/photocatalyst heterojunction has demonstrated an excellent capability for pollutant degradation under visible light irradiation. In this study, for the first time, highly stable colloidal dispersions of Bi/BiOClxBr1−x heterojunction with an exposed (001) facet are successfully prepared from inorganic simple salts using low‐frequency ultrasound irradiation (LFUI) at ambient conditions without further post‐treatment. The colloidal dispersion series of Bi/BiOClxBr1−x heterojunction (x = 0, 0.2, 0.5, 0.8 and 1) is simply obtained by adding stoichiometric aqueous solutions of NaCl and NaBr, into an acidic aqueous solution of Bi(NO)3.5H2O in a typical ultrasonication bath at room temperature within ≈5 min. Bi/BiOClxBr1−x heterojunction films are also fabricated using a simple drop‐casting technique and tested as immobilized photocatalytic reactors. Compared to its counterparts, the Bi/BiOCl0.8Br0.2 film possesses a 3D flower‐like morphology with a highly exposed (001) facet showing the highest electron‐hole generation and separation efficiencies. In addition, the Bi/BiOCl0.8Br0.2 film demonstrates the highest photocatalytic degradation rate of the rhodamine RhB aqueous solutions (≈5 ppm), achieving ≈99% in 60 min under the visible light component of the solar spectrum. This study demonstrates the potential of LFUI as a rapid scalable synthetic strategy for cost‐effective and energy‐efficient practical production of highly active immobilized photocatalytic reactors.

Combination therapy with low-frequency ultrasound irradiation and radiofrequency ablation as a synergistic treatment for pancreatic cancer

ABSTRACT We aim to evaluate the efficacies of combination therapy with low-frequency ultrasound-stimulated microbubbles (USMB) and radiofrequency ablation (RFA) on suppressing the proliferation of pancreatic cancer cell and treating Panc02 subcutaneous xenograft mice. The proliferation of HPDE6-C7 and Panc02 cells after the treatment of USMB and RFA alone or combination were evaluated by CCK-8 assay. Scratch test was performed to assess the cell migration capability. Panc02-bearing mice were received 14-day treatment of USMB and RFA alone or combination. Tumor size and survival rate were recorded once two days. The serum levels of immune-related factors and changes of apoptosis- and autophagy-related factors were detected by ELISA and western blotting methods. As a result, CKK-8 assays revealed significant inhibition on Panc02 cell proliferation in combination therapy with USMB and RFA relative to other groups (all p < 0.05). Strong synergistic effect of USMB combined with RFA was confirmed via the calculated combination index (CI) <0.4. In addition, combination therapy of USMB and RFA significantly inhibited the migration of Panc02 cells. Moreover, combined treatment remarkably inhibited the size and width of xenograft and improved the survival in Panc02-bearing mice. Furthermore, 14-day combination therapy of USMB and RFA in Panc02-bearing mice significantly facilitated the apoptosis and autophagy of tumor cells. In summary, combination therapy of USMB and RFA showed synergistic anti-tumor efficacies on Panc02 cells attributing to the promotion on apoptosis and autophagy in Panc02 subcutaneous xenograft mice.

Effect of cavitation intensity control on self-assembling of alkanethiols on gold in room temperature ionic liquids

This study investigates the effect of cavitation intensity on self-assembling of alkanethiol molecules on gold in room temperature ionic liquids (RTILs) under low frequency ultrasound irradiation (20 kHz). The use of RTILs, with low vapor pressure, enabled cavitation activity to be controlled up to quenching through pressure decrease within an argon-saturated atmosphere. This control possibility was used to acquire deeper insights into the role of cavitation on self-assembling processes. It was shown by electrochemical, contact angles and Polarization Modulation - Infrared Reflection Absorption Spectroscopy (PM-IRRAS) measurements that cavitation activates orientation and organization of self-assembled monolayers (SAM). X-ray Photoelectron Spectroscopy (XPS) revealed that, even if chemical adsorption of molecules is highly activated under ultrasound irradiation, it is not dependent on acoustic cavitation intensity.

Bifunctional Therapeutic Application of Low-Frequency Ultrasound Associated with Zinc Phthalocyanine-Loaded Micelles.

PurposeSonodynamic therapy (SDT) is a new therapeutic modality for the noninvasive cancer treatment based on the association of ultrasound and sonosensitizer drugs. Topical SDT requires the development of delivery systems to properly transport the sonosensitizer, such as zinc phthalocyanine (ZnPc), to the skin. In addition, the delivery system itself can participate in sonodynamic events and influence the therapeutic response. This study aimed to develop ZnPc-loaded micelle to evaluate its potential as a topical delivery system and as a cavitational agent for low-frequency ultrasound (LFU) application with the dual purpose of promoting ZnPc skin penetration and generating reactive oxygen species (ROS) for SDT.MethodsZnPc-loaded micelles were developed by the thin-film hydration method and optimized using the Quality by Design approach. Micelles’ influence on LFU-induced cavitation activity was measured by potassium iodide dosimeter and aluminum foil pits experiments. In vitro skin penetration of ZnPc was assessed after pretreatment of the skin with LFU and simultaneous LFU treatment using ZnPc-loaded micelles as coupling media followed by 6 h of passive permeation of ZnPc-loaded micelles. The singlet oxygen generation by LFU irradiation of the micelles was evaluated using two different hydrophilic probes. The lipid peroxidation of the skin was estimated using the malondialdehyde assay after skin treatment with simultaneous LFU using ZnPc-loaded micelles. The viability of the B16F10 melanoma cell line was evaluated using resazurin after treatment with different concentrations of ZnPc-loaded micelles irradiated or not with LFU.ResultsThe micelles increased the solubility of ZnPc and augmented the LFU-induced cavitation activity in two times compared to water. After 6 h ZnPc-loaded micelles skin permeation, simultaneous LFU treatment increased the amount of ZnPc in the dermis by more than 40 times, when compared to non-LFU-mediated treatment, and by almost 5 times, when compared to LFU pretreatment protocol. The LFU irradiation of micelles induced the generation of singlet oxygen, and the lipoperoxidation of the skin treated with the simultaneous LFU was enhanced in three times in comparison to the non-LFU-treated skin. A significant reduction in cell viability following treatment with ZnPc-loaded micelles and LFU was observed compared to blank micelles and non-LFU-treated control groups.ConclusionLFU-irradiated mice can be a potential approach to skin cancer treatment by combining the functions of increasing drug penetration and ROS generation required for SDT.

Combined ultrasound-ozone treatment for reutilization of primary effluent\u2014a preliminary study

The present work is a preliminary study on the potential of low-frequency ultrasound irradiation coupled with O3 process for the disinfection of a primary effluent from a municipal wastewater treatment plant preserving nutrient levels (in particular nitrogen and phosphorous), for its possible reuse in civil, industrial, and agricultural sectors. The treated water could be reused, after appropriate dilution, contributing to the circular economy perspective and reducing the need for both chemical fertilizer addition and freshwater supply. The effect of different specific ultrasonic energies and ozone doses was assessed on a bench-top system, composed of an ultrasonic reactor and a semi-batch ozonation vessel. The results showed that the combined US-O3 process produces a good removal efficiency regarding soluble Chemical Oxygen Demand, sCOD (ca. 60%), anionic surfactants (ca. 50%), and formaldehyde (ca. 50%), and an optimal abatement for Methylene Blue Active Substances (MBAS, > 90%). The process also reached high disinfection performances, obtaining 4 logs for E. coli and 5 log abatement for Total Coliforms. The high removal efficiency is matched by an outstanding retention of nutrients (total nitrogen and orthophosphate) highlighting a high potential value for agricultural reuse of the treated primary effluent, with possible significant saving of chemical fertilizers. It was concluded that low-frequency ultrasound pre-treatment, combined with ozonation, could be a useful process for primary effluent recovery for several purposes. Further studies are expected to be planned and executed to evaluate system scale-up feasibility.

Enhanced co-production of pectinase, cellulase and xylanase enzymes from Bacillus subtilis ABDR01 upon ultrasonic irradiation

The effect of low-intensity ultrasound irradiation was studied to improve the co-production for pectinase, cellulase, and xylanase enzymes using Bacillus subtilis ABDR01. Different parameters such as ultrasonic irradiation at the different growth phases of the bacterial strain, ultrasound power, irradiation duration, and irradiation duty cycle were assessed. Sonication with 90 W ultrasound power, 25 kHz frequency with 70 % duty cycle for 5 min at 6 h of bacterial growth phase gave the maximum productions of 87.82 U/ mL pectinase 22.17 U/ mL cellulase and 137.95 U/ mL xylanase respectively. The enzyme activity of pectinase, cellulase, and xylanase was enhanced by about 38.15 %, 53.77 %, and 24.59 %, respectively, compared to non-sonicated control cultivation. This optimized low-frequency ultrasound irradiation to bacterial cells enhanced the nutrient uptake rate and increased the cell wall permeability, which results in higher enzyme productivity. Our results signify the effectiveness of low-frequency ultrasound irradiation for improved enzyme yields and hyperactivation during microbial fermentation.

Ultrasound cavitation intensified amine functionalization: A feasible strategy for enhancing CO2 capture capacity of biochar

This paper describes a two-stage biochar activation process for CO2 capture, which includes acoustic treatment and amination. Contrarily to traditional carbon activation at temperatures above 700 °C, both stages of the current process are conducted at or near room temperature. It is known that CO2 can be fixed on the edge carbons of polycyclic aromatics hydrocarbons (PAHs) through thermal and reductive photo-carboxylation. Our previous work on biochar suggested that carbon of CO2 could be chemically fixed on biochar through acoustic or photochemical treatment of biochar in water/CO2 systems under ambient conditions. Separately, the graphene oxide (GO) literature reveals that carboxylic acids, epoxy and hydroxyl groups on biochar surface often serve as the active sites for converting GO to a new family of chemicals; amines are commonly grafted on these groups in the functionalization. Biochar has graphite and graphitic oxide clusters that consist of the oxygen functional groups mentioned above. These oxygen functionalities can be utilized for CO2 adsorption when functionalized with amine. Thus, the present study focuses on maximizing the CO2 capture capacity by manipulating the physicochemical structure of a pinewood-derived biochar. In this two-stage process, 30 s sonication at ambient temperature was applied to physically activate biochar prior to functionalization. Low-frequency ultrasound irradiation exfoliates and breaks apart the irregular graphitic layers of biochar, and creates new/opens the blocked microspores, thus enhancing the biochar’s porosity and permeability that are the keys in functionalization and subsequent CO2 capture. The sono-modified biochar was then functionalized with tetraethylenepentamine (TEPA) in the presence of two activating agents. The changes in surface characteristics, functional groups, graphene-like structure, and functionalization using activating agents were examined in detail and the capacity of the final products in CO2 removal was tested. The experimental results revealed that CO2 capture capacity, from a flow containing 10 and 15 vol% CO2, was almost 7 and 9 times higher, respectively, for ultrasound-treated amine-activated biochar, compared to raw biochar. The optimum capacity was 2.79 mmol/g at 70 °C and 0.15 atm CO2 partial pressure. Cyclic adsorption and desorption tests revealed that the CO2 capture capacity decreased 44% after 15 cycles.

Upregulation of Beclin-1 expression in DU-145 cells following low-frequency ultrasound irradiation combined with microbubbles.

Castration-resistant prostate cancer (PCa) is difficult to treat. Autophagy, which is an evolutionarily conserved mechanism, plays an important role in cancer development. The balance between cell death and survival in different stages varies in cancer development. The role of autophagy in PCa development has not yet been fully elucidated. Ultrasound may be of value in the treatment of PCa. The aim of the present study was to investigate the association between autophagy and ultrasound combined with microbubbles. The MTT assay was used to evaluate cell viability. Autophagy was observed by transmission electron microscopy. Reverse transcription-polymerase chain reaction and western blot analysis were used to assess the expression of autophagy-related genes. The results revealed that cell viability was significantly reduced by ultrasound combined with microbubbles in DU145 PCa cells. The present study demonstrated that ultrasound combined with microbubbles induced autophagy and autophagy-related DU-145 cell death. Notably, these findings highlighted additional mechanisms that suggest the potential of ultrasound-modulated autophagy as a novel therapeutic strategy for PCa.

Sonoporation: Gene transfer using ultrasound.

Genes can be transferred using viral or non-viral vectors. Non-viral methods that use plasmid DNA and short interference RNA (siRNA) have advantages, such as low immunogenicity and low likelihood of genomic integration in the host, when compared to viral methods. Non-viral methods have potential merit, but their gene transfer efficiency is not satisfactory. Therefore, new methods should be developed. Low-frequency ultrasound irradiation causes mechanical perturbation of the cell membrane, allowing the uptake of large molecules in the vicinity of the cavitation bubbles. The collapse of these bubbles generates small transient holes in the cell membrane and induces transient membrane permeabilization. This formation of small pores in the cell membrane using ultrasound allows the transfer of DNA/RNA into the cell. This phenomenon is known as sonoporation and is a gene delivery method that shows great promise as a potential new approach in gene therapy. Microbubbles lower the threshold of cavity formation. Complexes of therapeutic genes and microbubbles improve the transfer efficiency of genes. Diagnostic ultrasound is potentially a suitable sonoporator because it allows the real-time monitoring of irradiated fields.

Low-Frequency Ultrasound Irradiation Increases Blood–Tumor Barrier Permeability by Transcellular Pathway in a Rat Glioma Model

Low-frequency ultrasound (LFU) irradiation under certain acoustic intensity can increase blood-brain barrier permeability non-invasively and reversibly. The aim of this study was to find out the effect of LFU irradiation on blood-tumor barrier (BTB) permeability in rat C6 glioma model and the possible mechanism. In this research, Evans blue and H&E staining were used to evaluate the optimal parameter of LFU to open the BTB without damaging the normal brain tissue. Transmission electron microscopy was used to observe the changes of the number of pinocytotic vesicles in cerebral or glioma microvascular endothelial cells. The phosphorylation of tyrosine kinase Src, caveolin-1, and caveolin-2 was detected by western blot. The distribution and expressing levels of caveolae proteins, caveolin-1 and caveolin-2, were detected by immunohistochemical and immunofluorescent staining, RT-PCR, and western blot. Our research data showed that, in rat C6 glioma model, LFU irradiation at a frequency of 1 MHz, a power of 12 mW, and exposure time of 20 s induced the increase of BTB permeability temporally, which reached a peak at 1.5 h, then decreased and restored to normal level at 12 h after LFU irradiation. In the glioma microvascular endothelial cells of rat glioma model, LFU irradiation induced a significant increase of the pinocytotic vesicles' density. The phosphorylation of Src, caveolin-1, and caveolin-2 began to increase at 0.5 h and reached a maximum at 1 h. Immunohistochemical and immunofluorescent staining showed that caveolin-1 and caveolin-2 were co-localized in the glioma microvascular endothelial cells and glioma cells. The mRNA and protein expression levels of caveolin-1 and caveolin-2 were up-regulated, reached the peak value at 1.5 h, and re-normalized at 12 h after LFU irradiation. These results demonstrated that LFU irradiation increased BTB permeability by promoting transcellular transport in glioma microvascular endothelial cells. The phosphorylation of tyrosine kinase Src, caveolin-1, caveolin-2 and up-regulation of caveolin-1 and caveolin-2 were involved in LFU-induced caveolae-mediated endocytosis.

Sonoporation Delivery of Interleukin-27 Gene Therapy Efficiently Reduces Prostate Tumor Cell Growth In Vivo

We have examined the potential of a novel cytokine, interleukin-27 (IL-27), for gene therapy of prostate cancer. IL-27 is the most recently characterized member of the family of heterodimeric IL-12-related cytokines and has shown promise in halting tumor growth and mediating tumor regression in several cancer models. In the present study, we examined the efficacy of a new mode of gene delivery to prostate tumors: low-frequency ultrasound irradiation or "sonoporation." We also examined the potential of IL-27 gene delivery by sonoporation to treat and reduce the growth of prostate cancer in vivo. We used three models of immune-competent prostate adenocarcinoma and characterized the tumor-growth reduction, gene-profile expression, and effector cellular profiles. Our results suggest that IL-27 can be effective in reducing tumor growth and can help enhance accumulation of effector cells in prostate tumors in vivo. These results are promising, because they are potentially relevant to developing novel therapies that can be translated by using the novel and effective sonoporation gene-therapy delivery strategy.

Increasing of Blood-tumor Barrier Permeability through Paracellular Pathway by Low-frequency Ultrasound Irradiation In Vitro

The research was conducted to study the increase of blood-tumor barrier (BTB) permeability through paracellular pathway by low-frequency ultrasound (LFU) irradiation in vitro. LFU (frequency=1.0 MHz) was performed to irradiate BTB model from the co-culture of rat C6 glioma cells and rat brain microvascular endothelial cells (RBMECs). The permeability of BTB was measured by transendothelial electrical resistance (TEER) and flux of horseradish peroxidase (HRP) assays after LFU irradiation. Western-blotting, immunohistochemistry, and immunofluorescence assays were used to investigate the changes of expressions and distributions of tight junction (TJ)-associated proteins ZO-1, occludin, and claudin-5. The TEER value began to decrease, and the minimum value appeared at 2 h, then gradually returned to the original level at 24 h after LFU irradiation. With time, flux of HRP gradually increased and reached the peak 2 h after LFU irradiation. The expressions of ZO-1, occludin, and claudin-5 in RBMECs decreased, and decreased most significantly at 2 h, then gradually restored to the original level at 24 h. Meanwhile, they were discontinuously distributed in the cellular boundaries after LFU irradiation. In summary, the expression of TJ-associated proteins was down-regulated, TJ was opened, and the permeability of BTB was increased through paracellular pathway by LFU irradiation.

Effects of combining low frequency ultrasound irradiation with papaverine on the permeability of the blood–tumor barrier

This study was performed to determine whether low frequency ultrasound (LFU) irradiation, Papaverine (PA) infusion and combination LFU irradiation with PA infusion opened the blood-tumor barrier (BTB) by affecting tight junctions (TJ)-associated proteins zonula occluden-1 (ZO-1), occludin and caludin-5. In a rat brain glioma model, we found that the mRNA and protein expression levels of ZO-1, occludin and claudin-5 were decreased by LFU irradiation and PA infusion. LFU-induced and PA-induced decrease of ZO-1, occludin and claudin-5 was further decreased after combining LFU irradiation with PA infusion. Immunohistochemistry assay showed that the decreased expression of ZO-1, occludin and claudin-5 was the most obvious in the tumor capillaries. Meanwhile, Evans blue assay showed that the permeability of BTB was increased, and transmission electron microscopy (TEM) indicated that TJ was opened. This led to the conclusion that LFU irradiation and PA infusion together can open the BTB by paracellular pathway. Significantly down-regulated expression levels of ZO-1, occludin and claudin-5 might be one of the molecular mechanisms of combining LFU and PA enhancing the permeability of BTB.

Mechanisms of the increase in the permeability of the blood–tumor barrier obtained by combining low-frequency ultrasound irradiation with small-dose bradykinin

The research was conducted to study the characteristics of the noninvasive, reversible, targeted opening of the blood-brain barrier (BBB) by use of low-frequency ultrasound (LFU) irradiation and the selective opening of the blood-tumor barrier (BTB) by intracarotid infusion of bradykinin (BK) in small-dose, with the objective of exploring maximum opening of the BTB by combining LFU irradiation with BK infusion. Thus, it provides new therapeutic strategies for targeted transport of macromolecular or granular drugs to the brain. By using the rat C6 glioma model it was shown that extravasation of Evans blue (EB) through the BTB was significantly increased by combining LFU irradiation (frequency = 1.0 MHz, power = 12 mW, duration = 20 s) with intracarotid small-dose BK infusion, compared with utilizing the two methods separately. By transmission electron microscopy (TEM) we observed that this combination significantly increased the number of pinocytotic vesicles of brain microvascular endothelial cells (BMECs) in the BTB. An even more significant increase was observed by using RT-PCR, western blot, immunohistochemistry, and immunofluorescence to detect mRNA and changes of expression of the caveolae structure proteins caveolin-1 and caveolin-2 of BMECs. In summary, this research concludes that LFU irradiation and small-dose BK together selectively enhance the permeability of the BTB and increase the number of pinocytic vesicles of BMECs to a maximum. Significant up-regulation of the level of expression of caveolae structure proteins caveolin-1 and caveolin-2 might be the molecular mechanism of the co-enhanced endocytotic transport by BMECs. Thus, this research provides new therapeutic strategies for targeted transport of macromolecular drugs and the design of drugs.

Ultrasound absorption and entropy production in biological tissue: a novel approach to anticancer therapy

The entropy production of tumorous cells is higher than that of normal cells, and entropy flow is therefore directed from tumorous toward healthy cells. This results in information concerning the cancer propagating into the surrounding normal tissue. However, ultrasound absorption results in additional entropy production in tissues. The entropy mechanism possibly provides a basis for a novel approach to anticancer therapy through the use of ultrasound irradiation.Through the calculation of ultrasound-induced entropy production and comparison of the theoretical results with the experimental data on ultrasound absorption in biological tissues, we have demonstrated that ultrasound absorption will increase the entropy in normal tissue more efficiently than in tumorous tissue due to the more acidic nature of the latter. Consequently, the direction of entropy flow between these two kinds of cells may be reversed on exposure to ultrasound.The higher entropy accumulation of normal cells during ultrasound irradiation may possibly lead to a change in the original direction of entropy flow and avoid the propagation of information on the cancer into the normal tissues. We suggest that low-intensity, low-frequency ultrasound irradiation may be an efficient tool for the therapy of solid tumors.

Blood-Brain Barrier Disruption by Low-Frequency Ultrasound

HomeStrokeVol. 38, No. 2Blood-Brain Barrier Disruption by Low-Frequency Ultrasound Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBBlood-Brain Barrier Disruption by Low-Frequency Ultrasound Tibo Gerriets, MD and Maureen Walberer, DVM Max Nedelmann, MD Georg Bachmann, MD Manfred Kaps, MD Tibo GerrietsTibo Gerriets Department of Neurology, Justus Liebig University Giessen, Giessen, Germany, Kerckhoff-Clinic Bad Nauheim, Experimental Neurology Research Group, Bad Nauheim, Germany Search for more papers by this author and Maureen WalbererMaureen Walberer Department of Neurology, Justus Liebig University Giessen, Giessen, Germany, Kerckhoff-Clinic Bad Nauheim, Experimental Neurology Research Group, Bad Nauheim, Germany Search for more papers by this author Max NedelmannMax Nedelmann Department of Neurology, Johannes Gutenberg-University Mainz, Mainz, Germany Search for more papers by this author Georg BachmannGeorg Bachmann Department of Radiology, Kerckhoff-Clinic Bad Nauheim, Experimental Neurology Research Group, Bad Nauheim, Germany Search for more papers by this author Manfred KapsManfred Kaps Department of Neurology, Justus Liebig University Giessen, Giessen, Germany Search for more papers by this author Originally published14 Dec 2006https://doi.org/10.1161/01.STR.0000254444.19772.33Stroke. 2007;38:251Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: December 14, 2006: Previous Version 1 To the Editor:Dr Reinhard and coworkers report a case of cerebral gadolinium extravasation after 300 kHz ultrasound “treatment” using the same device that has been applied in the Transcranial Low-Frequency Ultrasound Mediated Thrombolysis in Brain Ischemia Study (TRUMBI) trial.1,2 This interesting observation improves our understanding of the underlying pathophysiology of the hemorrhagic complications that occurred in stroke patients during the TRUMBI study. The assumption that low-frequency ultrasound might cause blood-brain barrier disruptions and thus increase the risk of intracerebral hemorrhage—particularly in the presence of recombinant tissue plasminogen activator—appears convincing and is corroborated by our rat experiments using 20 kHz ultrasound.3 In this MRI study, low-frequency insonation caused a dose-dependant increase in T2-relaxation time which serves as an indicator for vasogenic brain edema and thus indicates blood-brain barrier disruption. Increased ultrasound energy, furthermore, caused circumscript cortical hemorrhagic lesions that appeared like traumatic cerebral contusions histologically. These findings suggest that mechanical ultrasound effects might be responsible for blood-brain barrier disruptions and bleeding complications. Because mechanical effects decrease with higher frequencies, we would recommend the use of ultrasound frequencies in the upper kHz range (ie, >300 kHz) for treatment purposes. Extensive preclinical evaluation of new devices, however, is obligatory.DisclosuresNone.1 Reinhard M, Hetzel A, Kruger S, Kretzer S, Talazko J, Ziyeh S, Weber J, Els T. Blood-brain barrier disruption by low-frequency ultrasound. Stroke. 2006; 37: 1546–1548.LinkGoogle Scholar2 Daffertshofer M, Gass A, Ringleb P, Sitzer M, Sliwka U, Els T, Sedlaczek O, Koroshetz WJ, Hennerici MG. Transcranial low-frequency ultrasound-mediated thrombolysis in brain ischemia: increased risk of hemorrhage with combined ultrasound and tissue plasminogen activator: results of a phase II clinical trial. Stroke. 2005; 36: 1441–1446.LinkGoogle Scholar3 Schneider F, Gerriets T, Walberer M, Mueller C, Rolke R, Eicke BM, Bohl J, Kempski O, Kaps M, Bachmann G, Dieterich M, Nedelmann M. Brain edema and intracerebral necrosis caused by transcranial low-frequency 20-kHz ultrasound: a safety study in rats. Stroke. 2006; 37: 1301–1306.LinkGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Teng Y, Jin H, Nan D, Li M, Fan C, Liu Y, Lv P, Cui W, Sun Y, Hao H, Qu X, Yang Z and Huang Y (2018) In vivo evaluation of urokinase-loaded hollow nanogels for sonothrombolysis on suture embolization-induced acute ischemic stroke rat model, Bioactive Materials, 10.1016/j.bioactmat.2017.08.001, 3:1, (102-109), Online publication date: 1-Mar-2018. Fan L, Liu Y, Ying H, Xue Y, Zhang Z, Wang P, Liu L and Zhang H (2010) Increasing of Blood-tumor Barrier Permeability through Paracellular Pathway by Low-frequency Ultrasound Irradiation In Vitro, Journal of Molecular Neuroscience, 10.1007/s12031-010-9479-x, 43:3, (541-548), Online publication date: 1-Mar-2011. Kyle A (2010) Correlation of acoustic pressure with BBB disruption 2010 39th Annual Ultrasonic Industry Association Symposium (UIA), 10.1109/UIA.2010.5506063, 978-1-4244-7947-4, (1-3) Nedelmann M, Gerriets T and Kaps M (2008) Therapeutische Ultraschallbehandlung des akuten HirnarterienverschlussesTherapeutic ultrasound of acute cerebral artery occlusion, Der Nervenarzt, 10.1007/s00115-008-2550-y, 79:12, (1399-1406), Online publication date: 1-Dec-2008. Nedelmann M, Reuter P, Walberer M, Sommer C, Alessandri B, Schiel D, Ritschel N, Kempski O, Kaps M, Mueller C, Bachmann G and Gerriets T (2008) Detrimental Effects of 60 kHz Sonothrombolysis in Rats with Middle Cerebral Artery Occlusion, Ultrasound in Medicine & Biology, 10.1016/j.ultrasmedbio.2008.06.003, 34:12, (2019-2027), Online publication date: 1-Dec-2008. February 2007Vol 38, Issue 2 Advertisement Article InformationMetrics https://doi.org/10.1161/01.STR.0000254444.19772.33PMID: 17170362 Originally publishedDecember 14, 2006 PDF download Advertisement

Reactions of 1,3,2,4-Dithiadiphosphetane-2,4-disulfides with Alkyl Borates

New boron derivatives of dithiophosphonic acids 3a–c and 5 were obtained in the reactions of Lawesson's reagent 1a and its homologue 1b with trialkyl borates 2a–c and O-isobutyl diphenylborate 4. Low frequency ultrasound irradiation (22 kHz, power 130 W) leads to reduction in reaction temperature and time in the reactions studied. The prepared compounds were identified by IR, 1H, and 31P NMR and mass spectra as well as elemental analyses.