Free radical formation induced by ultrasound and its biological implications

Riesz, Peter; Kondo, Takashi

doi:10.1016/0891-5849(92)90021-8

Cited by 598 publications

(319 citation statements)

References 147 publications

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“…1,36 The reversion of the predominantly nonfixative ethylene glycol to the fixative formaldehyde depends on the latter forming bonds with the tissue molecules. But the crosslinking reaction between formaldehyde and amino acids or nucleic acids is very slow.…”

Section: Discussionmentioning

confidence: 99%

Ultrasound-accelerated formalin fixation of tissue improves morphology, antigen and mRNA preservation

et al. 2005

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Formalin fixation and paraffin embedding are conventional tissue preservation and processing methods used for histologic diagnosis in over 90% of cases. However, formalin fixation has three disadvantages: (1) slow fixation (16-24 h) hinders intraoperative decision making, (2) slow quenching of enzymatic activity causes RNA degradation, and (3) extensive molecule modification affects protein antigenicity. Applying high-frequency, high-intensity ultrasound to the formalin fixative cuts fixation time to 5-15 min. Fixation of various tissues such as lymph node, brain, breast, and prostate suggests that, compared to the conventional method, implementation of ultrasound retains superior and more uniform tissue morphology preservation. Less protein antigenicity is altered so that rapid immunohistochemical reactions occur with higher sensitivity and intensity, reducing the need for antigen retrieval pretreatment. Better RNA preservation results in stronger signals in in situ hybridization and longer RNA fragments extracted from fixed tissues, probably due to rapid inhibition of endogenous RNase activity. Molecules extracted from ultrasound-fixed tissues are of greater integrity and quantity compared to conventionally fixed tissues, and thus better support downstream molecular analyses. Overall, ultrasound-facilitated tissue preservation can provide rapid and improved morphological and molecular preservation to better accommodate both traditional and molecular diagnoses.

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Section: Discussionmentioning

confidence: 99%

Ultrasound-accelerated formalin fixation of tissue improves morphology, antigen and mRNA preservation

et al. 2005

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“…This causes sonoporation to allow materials such as DNA, exterior to the cell, to enter. 31,32 In our study, a microbubble contrast agent containing albumin-stabilized perfluorocarbon gas filled microspheres (Optison) that has been established for safe clinical use was employed for efficient transfection. 15,33 Microbubbles collapse by insonation and the gas bodies are removed from the circulation within about 5 min in mice and 15 min in humans.…”

Section: Discussionmentioning

confidence: 99%

Ultrasound-contrast agent mediated naked gene delivery in the peritoneal cavity of adult rat

et al. 2007

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Gene transfer into the peritoneal cavity by nonviral methods may provide an effective therapeutic approach for peritoneal diseases. Herein, we investigated the feasibility and the effectiveness of ultrasound-microbubble-mediated delivery of naked plasmid DNA into the peritoneal cavity in rats. Following the intraperitoneal or the intravenous administration of a mixture of plasmid DNA (100 mg) and ultrasound contrast agent microbubbles, an ultrasound transducer was applied on the abdominal wall. The reporter pTRE plasmid encoding Smad7 was used to evaluate transfection efficiency. Smad7 expression was induced by doxycycline in drinking water. We detected less than 10% apoptotic cells and no inflammatory reaction in peritoneal tissues following the ultrasound-microbubble-mediated transfection. More importantly, the insonation significantly improved the transfection efficiency in peritoneal tissues. The transfection efficiency by intraperitoneal delivery route was higher than the intravenous route. The reporter gene, pTRE-Smad7, was readily detected in the parietal peritoneum, mesentery, greater omentum and adipose tissue. The peak of transgene expression occurred 2 days after transfection and the transgene expression diminished in a time-dependent manner thereafter. Overall, the effectiveness and simplicity of the ultrasound-microbubble-mediated system may provide a promising nonviral means for improving gene delivery for treating peritoneal diseases in vivo.

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“…Another disadvantage of using free DNA is that ultrasound causes DNA fragmentation [28,65] that reduces the transfection efficiency [57]. Complexing the DNA plasmids with cationic polymers such as poly(ethylene imine) and poly(L-lysine) preserves the integrity of the DNA upon exposure to 20 kHz ultrasound [57].…”

Section: Free Genetic Materialmentioning

confidence: 99%

Ultrasonic drug delivery – a general review

Pitt

Husseini

Staples

2004

Expert Opinion on Drug Delivery

557

428

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Ultrasound (US) has an ever-increasing role in the delivery of therapeutic agents including genetic material, proteins, and chemotherapeutic agents. Cavitating gas bodies such as microbubbles are the mediators through which the energy of relatively non-interactive pressure waves is concentrated to produce forces that permeabilize cell membranes and disrupt the vesicles that carry drugs. Thus the presence of microbubbles enormously enhances delivery of genetic material, proteins and smaller chemical agents. Delivery of genetic material is greatly enhanced by ultrasound in the presence of microbubbles. Attaching the DNA directly to the microbubbles or to gas-containing liposomes enhances gene uptake even further. US-enhanced gene delivery has been studied in various tissues including cardiac, vascular, skeletal muscle, tumor and even fetal tissue. US-enhanced delivery of proteins has found most application in transdermal delivery of insulin. Cavitation events reversibly disrupt the structure of the stratus corneum to allow transport of these large molecules. Other hormones and small proteins could also be delivered transdermally. Small chemotherapeutic molecules are delivered in research settings from micelles and liposomes exposed to ultrasound. Cavitation appears to play two roles: it disrupts the structure of the carrier vesicle and releases the drug; it also makes the cell membranes and capillaries more permeable to drugs. There remains a need to better understand the physics of cavitation of microbubbles and the impact that such cavitation has upon cells and drug-carrying vesicles.

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Free radical formation induced by ultrasound and its biological implications

Cited by 598 publications

References 147 publications

Ultrasound-accelerated formalin fixation of tissue improves morphology, antigen and mRNA preservation

Ultrasound-accelerated formalin fixation of tissue improves morphology, antigen and mRNA preservation

Ultrasound-contrast agent mediated naked gene delivery in the peritoneal cavity of adult rat

Ultrasonic drug delivery – a general review

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