[The influence of the main components of the ultraphonophoresis phytocomplex method on the release of the biologically active substances (an experimental study)]. / Vliianie osnovnykh komponentov metoda ul'trafonoforeza fitokompleksa na vysvobozhdenie biologicheski aktivnykh veshchestv (éksperimental'noe issledovanie).

The present study was designed to investigate kinetics of flavonoidrelease from the working compositions containing a phytocomplex. The basic parameters of this processes during phonophoresis were determined in the model in vitro experiments. The study has demonstrated the dependence of the flavonoid release rate on their initial concentration in the working compositions and the influence of dimethylsulfoxide (as well as the main and auxiliary agents of the working composition) on the release of biologically active substances. The technological methods designed for the enhancement of the effectiveness of the phytocomplex phonophoresis technique are proposed.

Ultrasound associated with caffeine increases basal and beta-adrenoceptor response in adipocytes isolated from subcutaneous adipose tissue in pigs.

BACKGROUND: The topical use of caffeine has been indicated for the lipodystrophies treatment as it promotes increased lipolysis. Ultrasound (US) is often used in cutaneous diseases, esthetic conditions, and as a skin permeation enhancer. OBJECTIVE: We investigate the lipolytic response of adipocytes isolated from subcutaneous adipose pigs tissue subjected to treatment with topical application of phonophoresis associated with caffeine. METHOD: We treated dorsal regions of pigs (Landrace × Large White, 35 days, 15 kg, n = 6) daily for 15 days with gel, gel + US [3 MHz, continuous, 0.2 Wcm(2), 1 min/cm(2), in total 2 min], gel + caffeine (5%w/w), and gel + caffeine + US. We used a fifth untreated region as control. Twenty-four hours after the last application, we isolated the adipocytes of each treated area and quantified the basal and stimulated lipolytic responses to isoprenaline. The results, in µmol glycerol/10(6)cells/60 min, were analyzed with analysis of variance or ANOVA followed by Newman-Keuls test. The value of p < 0.05 was indicative of statistical difference. RESULTS: Only the adipocytes isolated from the area treated with caffeine + US showed increased basal lipolysis (0.76 ± 0.26; p = 0.0276) and maximal isoprenaline stimulation (0.38 ± 0.15, p = 0.0029) compared with the other areas. CONCLUSION: The results demonstrate that increased lipolysis of caffeine + US is due to an increase in basal and beta-adrenoceptor response by caffeine, and caffeine's effect is local, avoiding unwanted effects.

[The rationale for the conservative treatment of chronic tonsillitis in the patients of the older age groups by the «soft¼ therapy methods]. / Obosnovanie konservativnogo lecheniya khronicheskogo tonzillita u lits starshikh vozrastnykh grupp metodami «myagkoi¼ terapii.

The objective of the present study was to develop an efficient system for the treatment of chronic tonsillitis in the patients of advanced and middle age based on the application of polyvalent bacteriophages in the combination with the physical factors and herbal medicines. The study involved 65 patients (39 women and 276 men) at the age from 65 to 73 years presenting with chronic tonsillitis. The treatment included washing the tonsillar lacunae with herbal infusion consisting of a tetterwort (Choledoniummajus) extract. This procedure was followed by phonophoresiswith the use of the combined polyvalent bacteriophage preparation in the non-liquid formulation during 7-10 days. The effectiveness of such treatment was evaluated based on the results of clinical examination and the analysis of the subjective feelings reported by the patients. In addition, the rosette-forming function of lymphocytes was estimated and palatine tonsil microbiotas in different patients were compared. The effectiveness of therapy was estimated at 89.2%. The positive outcome of the proposed treatment was documented in 78.6% of the cases within 6 months after the onset of therapy. It is concluded that the treatment of chronic tonsillitis with bacteriophagal preparations and herbal infusions in combination with thetraditionallow-frequency ultrasound treatment is highly efficacious (favourable outcome in 78.6% of the patients of middle and advanced age) without the use of antibiotic medications.

Evaluation of polyherbal gel for musculoskeletal injuries in industrial workers.

BACKGROUND: Industrial workers often have musculoskeletal disorders due to the nature of their work. OBJECTIVE: The goal was to investigate the scientific use of polyherbal gel in relieving pain and stiffness due to musculoskeletal injuries and improving activities of daily living (ADLs) in industrial workers. METHODS: A pragmatic, single-blinded, randomized control study divided 200 musculoskeletal injury patients into four parallel groups (n = 50). Groups 1 and 2 were applied polyherbal gel via phonophoresis with therapeutic ultrasound and superficial massage. Groups 3 and 4 received diclofenac diethyl-ammonium 1% gel by phonophoresis and superficial massage. The Global Pain Relief Scale, Numeric Pain Rating Scale (NPRS), and Western Ontario and McMaster Universities Arthritis Index (WOMAC) were used to measure pain, stiffness, and ADLs. Data was analyzed using one-way analysis of variance (ANOVA) and paired t-test to compare mean±SD of four independent groups before and after gel application. The confidence interval was 95%, with p < 0.05 considered significant. RESULTS: The results revealed that polyherbal gel reduced pain (NPRS, WOMAC and Global pain relief scales) more efficiently (p≤0.000) when applied with phonophoresis as compared to applied with massage and standard diclofenac (p≤0.005), furthermore, polyherbal gel when applied with phonophoresis showed more efficient results. CONCLUSION: Industrial workers with musculoskeletal injuries benefited from the use of polyherbal gel for pain and inflammation relief. The polyherbal gel is natural, cost-effective, and easy to formulate.

Comparison of the efficacy of ketoprofen phonophoresis, ultrasound, and short-wave diathermy in knee osteoarthritis.

The present study aimed to compare the efficacy of three different deep heating modalities: phonophoresis (PH), short-wave diathermy (SWD), and ultrasound (US), in knee osteoarthritis. Patients who consented to participate in the study were randomly divided into the following three groups. Group 1 (n = 33) received PH, Group 2 (n = 33) received US, and Group 3 (n = 35) received SWD. These deep heating therapies were applied by the same therapist. Each therapy began with 20-min hot pack application. Each of the three physical therapy modalities was applied 5 days a week for 2 weeks (a total of 10 sessions). The patients were evaluated using visual analogue scale (VAS) at rest, 15-m walking time, and the Western Ontario and McMaster Universities Arthritis Index (WOMAC) both before and after the treatment. Moreover, at the end of the treatment, both the physician and the patient made an overall evaluation, by rating the treatment efficacy. The results of the study showed that VAS, 15-m walking time, and WOMAC parameters were improved with all three deep heating modalities, and all the three modalities were effective. However, there was no significant difference between the three modalities in terms of efficacy. There was also no significant difference between the three groups in terms of post-treatment general evaluation of the physician and the patient. The present study is the first to suggest that choosing one of PH/US/SWD therapy options would provide effective results and none of them are superior to the others, and we believe that these findings will be a basis for further studies.

The effect of sonophoresis on topical anesthesia: a pilot project.

The dental anesthesia sonophoresis device (DASD) is a novel device that is intended to reduce the discomfort associated with intraoral mucosa needle puncture. The DASD produces ultrasonic energy that provides a sonophoretic effect on the oral mucosa, generating microchannels through the lipids between the keratinized cells that make up the stratum corneum. Once the topical anesthetic has permeated the stratum corneum, it quickly diffuses through the soft tissue, desensitizing the nerve endings and reducing the perception of pain caused by needle penetration. The aim of this study is to evaluate whether topical anesthesia applied using the DASD will reduce the discomfort of the needle puncture when compared to the control device. A split-mouth model, using 50 healthy subjects with puncture site at the maxillary canine vestibule, was used for this study. Subjects received a needle puncture on both sides of the mouth. Prior to the needle puncture, there was randomized application of 5% lidocaine with the DASD and a control device. Subjects rated their discomfort after needle punctures utilizing the visual analog scale pain scoring system. There was no statistically significant difference in the pain perception using the DASD versus the control device.

[Extracorporeal shock wave therapy in athletes with degenerative and dystrophic disorders of locomotory system].

Degenerative and dystrophic changes of joints and ligaments are among the most prevalent disorders in professional athletes. Specification of a complex system for these diseases is an important task in sports medicine. Extracorporeal shock wave therapy is a modern and highly effective method of rehabilitation.

The effects of pressure release, phonophoresis of hydrocortisone, and ultrasound on upper trapezius latent myofascial trigger point.

OBJECTIVE: To compare the effects of pressure release (PR), phonophoresis of hydrocortisone (PhH) 1%, and ultrasonic therapy (UT) in patients with an upper trapezius latent myofascial trigger point (MTP). DESIGN: Repeated-measure design. SETTING: A pain control medical clinic. PARTICIPANTS: Subjects (N=60; mean±SD age, 21.78±1.76y) with a diagnosis of upper trapezius MTP participated in this study. Subjects were randomly divided into 4 groups: PR, PhH, UT, and control (15 in each group). All patients had a latent MTP in the upper trapezius muscle. INTERVENTIONS: PR, PhH, UT. MAIN OUTCOME MEASURES: Subjective pain intensity, pain pressure threshold (PPT), and active cervical lateral flexion range of motion were assessed in 6 sessions. RESULTS: All 3 treatment groups showed decreases in pain and PPT and an increase in cervical lateral flexion range of motion (P<.001) compared with the control group. Both PhH and PR techniques showed more significant therapeutic effects than UT (P<.001). CONCLUSIONS: Our results indicate that all 3 treatments used in this study were effective for treating MTP. According to this study, PhH is suggested as a new method effective for the treatment of MTP.

Tolerance of low-frequency ultrasound sonophoresis: a double-blind randomized study on humans.

BACKGROUND: Sonophoresis [low-frequency ultrasound (US)] has been used in animals and in vitro to investigate enhanced percutaneous absorption of drugs. No study focused on its clinical human tolerance has been published as yet. METHODS: We aimed to assess the bioeffects of low-frequency US in vivo on human skin in a double-blind randomized-controlled study. We applied pulse-mode US at 36 kHz for 5 min in a step procedure of increasing dosage, from 1.57 to 3.50 W/cm(2), and placebo. The primary outcome was toxic effects of the procedure, defined as a pain score >40 on a 0-100 mm visual analogue scale or necrosis. Erythema (scored from 0 to 3 in severity) was also evaluated. The secondary outcomes were measurements of skin thickness by high-resolution skin imaging, of skin capacitance and temperature. RESULTS: We included 34 healthy volunteers. We found no pain score >38 and no skin necrosis with either US or placebo. Erythema was systematically observed immediately after US application, but after 1 day, we observed three cases in the knee group. The most frequent adverse effect was tinnitus. We observed no marked increase in temperature or cutaneous thickness after US or placebo. Cutaneous capacitance increased immediately after both applications. CONCLUSION: Such data demonstrating good tolerance of sonophoresis can be useful before the initiation of a clinical trial of the therapeutic use of low-frequency sonophoresis in humans.

Assessment of phonophoresis and iontophoresis in the treatment of carpal tunnel syndrome: a randomized controlled trial.

To define the role of phonophoresis and iontophoresis of corticosteroids in conjunction with wrist splint use in the treatment of carpal tunnel syndrome (CTS) compared to wrist splint use alone, 52 CTS subjects were analyzed based on clinical and electrophysiological criteria. A prospective, randomized controlled trial was carried out to assess symptom severity, motor skills, and hand function according to the Boston Symptom Severity Scale (BSSS), grip strength, and nine-hole peg test (NHPT), respectively, on the initial visit and in the 3rd month after treatment. The patients underwent conservative interventions randomly as follows: (1) 3 weeks of phonophoresis with betamethasone in conjunction with wrist splint use (group I, n: 18) or (2) 3 weeks of iontophoresis with betamethasone in conjunction with wrist splint use (group II, n: 16) or (3) wrist splint use alone (control, group III, n: 18). The mean age of the patients was 43.7 ± 8.4 (range 24-57) years. Groups I, II, and III showed a significant and further improvement in BSSS at the 3rd month evaluations compared with baseline (P < 0.001, P = 0.001, P < 0.001, respectively), but no significant change was observed in grip strength or NHPT (P > 0.05). There was a statistically significant difference between the phonophoresis and control groups after treatment only regarding BSSS, in favor of phonophoresis (P = 0.012). We recommend the use of wrist splints especially with phonophoresis for relief of symptoms in patients with CTS. Our results demonstrated no superiority among the treatment groups. Further, transdermal steroid treatments are not key determinants of efficacy with respect to motor skills and hand dexterity.

Delivery of an angiogenic gene into ischemic muscle by novel bubble liposomes followed by ultrasound exposure.

PURPOSE: To develop a safe and efficient gene delivery system into skeletal muscle using the combination of Bubble liposomes (BL) and ultrasound (US) exposure, and to assess the feasibility and the effectiveness of BL for angiogenic gene delivery in clinical use. METHODS: A solution of luciferase-expressing plasmid DNA (pDNA) and BL was injected into the tibialis (TA) muscle, and US was immediately applied to the injection site. The transfection efficiency was estimated by a luciferase assay. The ischemic hindlimb was also treated with BL and US-mediated intramuscular gene transfer of bFGF-expressing plasmid DNA. Capillary vessels were assessed using immunostaining. The blood flow was determined using a laser Doppler blood flow meter. RESULTS: Highly efficient gene transfer could be achieved in the muscle transfected with BLs, and US mediated the gene transfer. Capillary vessels were enhanced in the treatment groups with this gene transfer method. The blood flow in the treated groups with this gene transfer method quickly recovered compared to other treatment groups (non-treated, bFGF alone, or bFGF+US). CONCLUSION: The gene transfer system into skeletal muscle using the combination of BL and US exposure could be an effective means for angiogenic gene therapy in limb ischemia.

Egg nutritional modulation with amino acids improved performance in zebrafish larvae.

New and more efficient methods to sustainably intensify Aquaculture production are essential to attain the seafood demand for direct human consumption in the near future. Nutrition has been identified as one strategy of early exposure that might affect animal early development and later phenotype. This strategy may have positive consequences in the modulation of fish digestive physiology, which will correlate with higher performance outputs. Thus, improving fish digestive efficiency will lead to higher productivity and lower biogenic emission from aquaculture facilities, minimising the impact on the environment while increasing the biological efficiency. An innovative in ovo nutritional modulation technique based on low-frequency ultrasounds was used to enhance the transport of amino acids across the embryo membranes. An early stimulus with either arginine or glutamine, both involved in gut maturation, was applied in zebrafish (Danio rerio) embryos at 3.5 hours post-fertilization (hpf). At 22 days post-fertilization (dpf), growth performance, digestive enzyme activities and gut microbiota composition were analysed to evaluate the larval nutrition-induced metabolic plasticity and the effects on fish digestive efficiency. Results showed that fish survival was not affected either by the sonophoresis technique or amino acid supplementation. Final dry weight at 22 dpf was statistically higher in larvae from glutamine treatment when compared to the control even with lower trypsin activity, suggesting a higher nutrient digestion capacity, due to a slightly modulation of gut microbiota. Higher arginine supplementation levels should be tested as strategy to enhance growth at later developmental stages. In conclusion, this study demonstrated the efficiency of sonophoresis technique for in ovo nutritional modulation and suggests that in ovo glutamine supplementation might promote growth at later developmental stage through a positive microbiota modulation.

Dexamethasone Sodium Phosphate Penetration During Phonophoresis at 2 Ultrasound Frequencies.

CONTEXT: The effect of ultrasound frequency on phonophoresis drug delivery in humans is unknown. OBJECTIVE: To determine if a low (45-kHz) or high (1-MHz) frequency delivered a higher dexamethasone (Dex) concentration through the skin. DESIGN: Controlled laboratory study. SETTING: Laboratory. PATIENTS OR OTHER PARTICIPANTS: A total of 40 healthy men between the ages of 18 and 45 years (age = 23.1 ± 2.6 years, height = 176.1 ± 7.2 cm, mass = 88.5 ± 19.4 kg, posterior calf subcutaneous thickness measured using musculoskeletal ultrasound imaging = 0.6 ± 0.2 cm). INTERVENTION(S): Participants were randomly assigned to 1 of 4 groups (ultrasound frequency at microdialysis probe depth): (1) 45-kHz frequency at 1 mm, (2) 45-kHz frequency at 4 mm, (3) 1-MHz frequency at 1 mm, or (4) 1-MHz frequency at 4 mm (n = 10 in each group). Three linear microdialysis probes were inserted at the desired tissue depth. We rubbed dexamethasone sodium phosphate (Dex-P) into the skin and then applied a 15-minute phonophoresis treatment. MAIN OUTCOME MEASURE(S): Dialysate was collected during the treatment and 60 minutes posttreatment and analyzed for Dex-P, Dex, and the metabolite form of Dex. The sum of the 3 analytes was calculated as total dexamethasone (Dex-total), and differences between the 45-kHz and 1-MHz treatment groups were determined by a repeated-measures analysis of variance. RESULTS: At 1 mm, 3 (30%) participants in the 45-kHz and 4 (40%) participants in the 1-MHz group had measurable levels of Dex-P. Total dexamethasone increased after the treatment ceased, independent of ultrasound frequency (P < .001), with a trend of the 45-kHz treatment to produce a greater increase in drug concentration (P = .006). At 4 mm, 5 (50%) participants in the 45-kHz and 1 (10%) participant in the 1-MHz group had measurable levels of Dex-P. We observed no difference in Dex-total concentration between treatment groups at 4 mm (P = .72). CONCLUSIONS: Phonophoresis provided a mechanism for Dex-total delivery at the 1- and 4-mm tissue depths. However, the effectiveness of the ultrasound frequencies varied between the 2 measured tissue depths.

Combined effect of sonophoresis and a microemulsion on the dermal delivery of celecoxib.

The aim of this study was to evaluate the intensity of sonophoresis at which the skin penetration of celecoxib was enhanced and to study the combined effects of sonophoresis and microemulsion application on the dermal delivery of celecoxib. The sonophoresis intensity that provided the highest skin penetration enhancement of celecoxib was 30 Watts/cm2. However, the combination of sonophoresis and the microemulsion resulted in a decrease in celecoxib skin penetration. The results of a confocal laser scanning microscopy study using the colocalization analysis of multifluorescently labeled particles revealed that the reduction in skin penetration of celecoxib from the combination of sonophoresis and a microemulsion resulted from a decrease in transfollicular penetration, which is the major skin absorption pathway of the microemulsion.

Phonophoresis of Phyllanthus amarus nanoparticle gel improves functional capacity in individuals with knee osteoarthritis: A randomized controlled trial.

OBJECTIVE: This study examined the effects of treatment with Phyllanthus amarus nanoparticle gel applied by phonophoresis (PP) and ultrasound therapy (UT) in patients with symptomatic knee osteoarthritis (OA) using a randomized, double-blind, controlled trial. METHODS: Patients with knee OA (n = 40; mean age ±â€¯SD, 64.30 ±â€¯9.71 years), who had visual analogue scale (VAS) scores for knee pain intensity of 68.00 ±â€¯9.58 (UT group) and 71.00 ±â€¯8.74 (PP group, respectively) before treatment, were randomly allocated into two groups. Both groups were treated with an ultrasound program in continuous mode, 1.0 W/cm2, 10 min per session, for 10 sessions. Nanoparticles of P. amarus were used in the PP group, whereas a nondrug coupling gel was used in the UT group. The 6-min walk test (6-MWT) was performed to evaluate functional capacity. The VAS and the 6-MWT were evaluated before and after 10 treatment sessions in both groups using a double-blind procedure. RESULTS: VAS and 6-MWT showed significant improvement after treatment in both groups (p < 0.05). The PP group showed more significant effects than the UT group, in terms of both reducing the VAS pain score (p < 0.05) and improving 6-MWT (p < 0.05). CONCLUSIONS: PP is suggested as an effective method for the treatment of symptomatic knee OA for reducing pain and improving functional capacity.

Topical application of (S)-(-)-limonene is as effective as phonophoresis for improving oxidative parameters of injured skeletal muscle in rats.

The aim of this study is to investigate the effects of limonene, alone or associated with therapeutic ultrasound, on oxidative stress following skeletal muscle injury. Thirty male Wistar rats were divided into 5 groups: CTR-control, MI-muscle injury without treatment, TPU-therapeutic pulsed ultrasound alone, TPU + LIM-phonophoresis with 5% limonene, and LIM-5% limonene applied topically. Muscle injury was induced by a mechanical abrupt impact over gastrocnemius muscle. The animals were treated in the following intervals: 2, 12, 24, 48, 72, and 96 h after injury. Blood and gastrocnemius samples were collected 98 h after lesion for data analysis. Creatine kinase (CK) and lactate dehydrogenase (LDH) activity, lipid peroxidation (TBARS) levels, catalase (CAT), and superoxide dismutase (SOD) activity were assessed. CK (p = 0.01), SOD activity (p < 0.01), and TBARS levels (p < 0.01) were increased after injury. There was no effect on LDH levels in any group. Phonophoresis (TABRS p < 0.01; SOD p = 0.01), TPU alone (TBARS p < 0.01; SOD p = 0.01), and LIM alone (TBARS p < 0.01; SOD p < 0.01) reduced TBARS levels and SOD activity after muscle injury. There was no change for CAT activity after injury. Only phonophoresis reduced CK activity after injury (p < 0.01). There was no difference between phonophoresis, TPU alone and LIM alone groups for TBARS, SOD, CAT, and LDH. Limonene alone and TPU alone were effective in reducing oxidative stress parameters after skeletal muscle injury. Only phonophoresis decreased CK activity. Skeletal muscle injury increases reactive oxidative species (ROS) levels and muscle proteins activity as creatine kinase (CK) and lactate dehydrogenase (LDH). Five percent limonene, alone or associated with therapeutic pulsed ultrasound, exhibited reduction of CK, superoxide dismutase (SOD) and catalase (CAT) activity, and lipid peroxidation markers (TBARS). Graphical abstract.

Sonophoresis: recent advancements and future trends.

OBJECTIVES: Use of ultrasound in therapeutics and drug delivery has gained importance in recent years, evident by the increase in patents filed and new commercial devices launched. The present review discusses new advancements in sonophoretic drug delivery in the last two decades, and highlights important challenges still to be met to make this technology of more use in the alleviation of diseases. KEY FINDINGS: Phonophoretic research often suffers from poor calibration in terms of the amount of ultrasound energy emitted, and therefore current research must focus on safety of exposure to ultrasound and miniaturization of devices in order to make this technology a commercial reality. More research is needed to identify the role of various parameters influencing sonophoresis so that the process can be optimized. Establishment of long-term safety issues, broadening the range of drugs that can be delivered through this system, and reduction in the cost of delivery are issues still to be addressed. SUMMARY: Sonophoresis (phonophoresis) has been shown to increase skin permeability to various low and high molecular weight drugs, including insulin and heparin. However, its therapeutic value is still being evaluated. Some obstacles in transdermal sonophoresis can be overcome by combination with other physical and chemical enhancement techniques. This review describes recent advancements in equipment and devices for phonophoresis, new formulations tried in sonophoresis, synergistic effects with techniques such as chemical enhancers, iontophoresis and electroporation, as well as the growing use of ultrasound in areas such as cancer therapy, cardiovascular disorders, temporary modification of the blood-brain barrier for delivery of imaging and therapeutic agents, hormone replacement therapy, sports medicine, gene therapy and nanotechnology. This review also lists patents pertaining to the formulations and techniques used in sonophoretic drug delivery.

[Investigation in vivo of effect of ultrasound-mediated microbubble destruction on entrance of feridex into the aortal wall].

OBJECTIVE: To explore feasibility for entrance of the contrast agent Sonovue and Feridex into the aortal wall. METHODS: 17 male Japanese giant ears rabbits (common grade), including 11 atherosclerosis (AS) animal models fed with food containing high-content lipid and normal animals fed with common food as control. Respectively, 10 animals in the AS group and 6 animals in the normal group were selected in a random way to undergo ultrasound-mediated microbubble destruction (UMMD) and no ultrasound-mediated microbubble destruction (-UMMD) half and half. One animal was administrated with double doses of Feridex. After general anesthesia, MR plain scan and intravenous injection of Feridex 100 micromol Fe/kg, immediately ultrasound focused on the front wall of the aortic arch, which underwent UMMD at the pressure of 3.5 Mpa with MI1.2 while 10 ml solution (Sonovue + normal saline)was injected intravenously at the speed of 0.5 ml/min FOR 20 min. 3T magnetic resonance (MR) was performed with a moderately T2* weighted gradient sequence. Enhanced scan were performed for 1 h, 24 h, 48 h, 72 h and after killing the animal. then the specimen were delivered to conduct optical and electronic microscope examination. Variance test for the re-measured data was adopted to verify the data obtained in every group. RESULTS: The effect of UMMD group on SPIO particles entrance into the aortal wall is of marked significance (P = 0.0004) statistically. The effect of UMMD on distribution in the vessel wall is of statistical significance (P = 0.01), more particles in the dventitia. Gas or microbubbles were found to enter into the intima, media of the aorta, and verified by Oil Red O staining. After staining the findings of iron particle in the cell and out of the cell are different. CONCLUSIONS: UMMD may facilitate entrance of those SPIO particles with a bigger diameter and microbubbles into the aortal wall. This discovery may provide a new solution for penetration of complex macromolecule probes and gene-carried drug through the tunica intima of the aorta.

Combined Confocal Microscope and Brandaris 128 Ultra-High-Speed Camera.

Controlling microbubble-mediated drug delivery requires the underlying biological and physical mechanisms to be unraveled. To image both microbubble oscillation upon ultrasound insonification and the resulting cellular response, we developed an optical imaging system that can achieve the necessary nanosecond temporal and nanometer spatial resolutions. We coupled the Brandaris 128 ultra-high-speed camera (up to 25 million frames per second) to a custom-built Nikon A1R+ confocal microscope. The unique capabilities of this combined system are demonstrated with three experiments showing microbubble oscillation leading to either endothelial drug delivery, bacterial biofilm disruption, or structural changes in the microbubble coating. In conclusion, using this state-of-the-art optical imaging system, microbubble-mediated drug delivery can be studied with high temporal resolution to resolve microbubble oscillation and high spatial resolution and detector sensitivity to discern cellular response. Combining these two imaging technologies will substantially advance our knowledge on microbubble behavior and its role in drug delivery.

Low-frequency sonophoresis: current status and future prospects.

Application of ultrasound enhances skin permeability to drugs, a phenomenon referred to as sonophoresis. Significant strides have been made in sonophoresis research in recent years, especially under low-frequency conditions (20 kHz