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.Key Words: Dental anesthesia sonophoresis device, SonophoresisSonophoresis, which is low-frequency ultrasound, has been shown to enhance transdermal transport of various drugs, including macromolecules. Enhancement from sonophoresis occurs by disordering the structured lipids in the stratum corneum. Although sonophoresis has been shown to be effective on the skin, its effect has not been studied intraorally. The development of the dental anesthesia sonophoresis device (DASD), a device whose design was specially developed for the application of sonophoresis in the oral cavity, has opened the door for exploration in the benefits and effectiveness of sonophoresis application in the dental field. Fear of intraoral local anesthetic injection is one of the main reasons people avoid dental treatment.¹ Many investigators, using a variety of different techniques, have explored reducing the pain and discomfort of the dental injection. The majority of research has focused on the application of topical anesthesia.The results are inconsistent with regard to the effectiveness of topically applied anesthetic. Some studies show that there are no significant differences when compared to the placebo.^2–5 On the other hand, there are several studies that support the efficacy of topical anesthetic.^3,6–9Duration of application has been isolated as an important factor to achieve adequate topical anesthesia. Meechan¹⁰ summarizes that the degree of topical anesthesia penetration and its effectiveness are governed by the duration of application. It has been suggested that success of topical anesthesia is guaranteed when used in the buccal fold of either jaw after a 5-minute application.¹¹ Due to the lack of consistency in the literature regarding the effectiveness of topical anesthesia, there is need for continued research and improvement.Topical anesthetic must cross the physical barrier of the intraoral mucosa to reach the underlying nerve receptors. The free nerve endings are located close to the basal surface of the oral epithelium.¹² The location of these free nerve endings only reinforces the importance of the topical anesthetic passing through the oral mucosa barrier. The intraoral mucosa, like the skin, consists of stratified squamous epithelium with different layers of cells. The most superficial layer is the stratum corneum, which is filled with short stacks of lipid lamellae.¹³ This lipid layer makes it difficult for substances to cross the stratum corneum. To demonstrate this, Squier¹⁴ showed that horseradish peroxidase could not penetrate the top 3 layers of the oral mucosa of 3 mammals when applied topically.Attempts have been made to improve the penetration of topical anesthetics across this anatomic barrier. Hutchins et al⁷ studied the effect of vibration with a placebo and vibration with 20% benzocaine on pain of intraoral injections, and found vibration had no effect on reducing pain. Others have studied the use of iontophoresis and phonophoresis for application of anesthesia.^15,16 Research suggests that skin anesthesia by application of a topical anesthetic can be expedited through iontophoresis; however, this still requires a minimum of 10 minutes at relatively high voltage.¹⁷Ultrasound has been shown to enhance transdermal transport of various drugs, including macromolecules. This type of enhancement is termed sonophoresis, indicating the enhanced transport of molecules under the influence of ultrasound.¹⁸The DASD is a novel device intended to expedite penetration of topical anesthetic with a faster onset of clinical effectiveness. The DASD is a portable, battery-powered device that simultaneously generates ultrasonic energy and sonic vibration in a small applicator head that can easily reach and adapt to injection sites in the oral cavity. The ultrasonic energy is in small bursts of 300–350 kHz that provide a sonophoretic effect on the oral mucosa. The manufacturer claims the DASD works by generating microchannels through the lipids in the stratum corneum. The sonic vibration is provided simultaneously with the ultrasonic energy in the form of sinusoidal motion ranging from 200–300 Hz. This vibration helps to randomize and distribute the sensation associated with the ultrasonic energy. Once the topical anesthetic has permeated the stratum corneum, it quickly diffuses through the soft tissue, desensitizing the nerve endings. The purpose 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. The null hypothesis is that there is no difference of perceived discomfort between the DASD and the control device (CD).     

The effect of He-Ne and Ga-Al-As laser light on the healing of hard palate mucosa of mice

Low-level laser therapy (LLLT) has been used to accelerate wound healing, yet questions remain concerning its therapeutic applications. This study aimed to compare the healing efficacy of helium-neon (He-Ne) red light (laser) and gallium aluminum arsenide (Ga-Al-As) infrared lasers at two different doses on hard palate wounds. In a randomized controlled study, 75 adult male mice were divided into five groups of 15 each, after undergoing identical surgical procedures; a control group, with no laser irradiation; HD1 and HD2 groups, treated with He-Ne laser (wavelengths 632.8 nm, power 5 mW, and spot size 0.02 cm²) at doses of 4 J/cm² and 7.5 J/cm² respectively; and GD1 and GD2 groups, treated with Ga-Al-As laser (wavelengths 830 nm, peak power 25 mW, and spot size 0.10 cm²) at the doses of 4 J/cm² and 7.5 J/cm², respectively. Five animals from each group were killed on the third, seventh, and 14 days after surgery, and biopsies were made for histological analysis. On the 3rd and 7th day after the surgery, the number of polymorphonuclear cells (PMN) in HD1, HD2, GD1, and GD2 groups was significantly lower than that of the control group. On the 7th and 14th day, the fibroblasts and new blood vessels counts and collagen density fibers in HD1, HD2, GD1, and GD2 groups were also significantly higher than that of the control groups, and the fibroblast counts and collagen density fibers in HD1 and HD2 groups were higher than that of the GD1 and GD2 groups. LLLT with He-Ne laser compared to Ga-Al-As laser has a positive healing effect on hard palate gingival wounds in mice regardless of the radiation dose.     

Morpholino Oligo Antisense efficiently suppresses BCR/ABL and cell proliferation in CML: specific inhibition of BCR-ABL gene expression by Morpholino Oligo Antisense in BCR-ABL(+) cells

Chronic myeloid leukemia is a disorder that develops when a hematopoietic stem cell acquires the Philadelphia chromosome carrying the chimeric BCR/ABL oncogene leading to a deregulated cell proliferation and a decreased apoptosis in response to mutagenic stimuli. Therefore, it has been considered that BCR/ABL oncogene is a potential attractive target for anticancer agents. Antisense strategies aiming to suppress the expression of BCR/ABL in chronic myeloid leukemia cells have been studied by several research groups over the last decade. In the present study, the effect of Morpholino Oligo Antisense in BCR/ABL oncogene silencing was evaluated. To examine the hypothesis, K562 was used as a BCR/ABL fusion gene positive cell line using a Jurkat cell line as a control. The capacity of Morpholino Oligo Antisense in inhibiting the translation of p210(bcr-abl) protein by a western blotting technique, inhibition of cell proliferation, and stimulation of apoptosis by flow cytometric analysis after 24 and 48 hours was studied. Prolonged exposure of K562 cell line to Morpholino Oligo Antisense targeted against BCR-ABL showed proliferation inhibition as the main feature. Following western blotting, we found that complete silencing of BCR-ABL had been achieved but flow cytometric analysis showed no significant apoptosis. The results indicate that Morpholino Oligo Antisense was able to inhibit p210(bcr-abl), but did not induce apoptosis due to co-silencing of BCR.     

Multi-detector computed tomography demonstration of double-lumen aortic arch--persistent fifth arch--as an isolated anomaly in an adult

Persistent fifth - double-lumen - aortic arch is a rarely seen entity, which is usually associated with other cardiac anomalies; it has been previously reported only in children. We report a new case of double-lumen aortic arch with a systemic-to-systemic connection diagnosed incidentally during cardiac multi-detector computer tomography evaluation of coronary artery bypass grafts in an adult.     

Serum lipids and chronic hepatitis C genotype 4: interaction and significance

Background &; aim. Metabolic abnormalities are common in chronic hepatitis C infection (CHC). However, the genotypic differences of these disarrangements in patients infected with CHC genotype 4 (HCV-4) and its association with liver histology and viral loads remain unknown.Material and methods. We consecutively enrolled 183 HCV-4 patients and 106 healthy matched controls; to compare metabolic profiles and assess pattern of association of HCV RNA levels as well as histological factors with the serum lipid profile.Results. HCV-4 infection is associated with higher homeostasis model assessment of insulin resistance (HOMA-IR) index, despite that, a favourable lipid pattern, consisting of an elevation in HDLC and a reduction in serum cholesterol (TC), LDL-C and triglyceride (TG) levels, in comparison with normal matched adults. Significant fibrosis was independently associated with HOMA-IR, portal/periportal inflammation grade, serum cholesterol and age. Univariate association was elucidated between lower LDL-C and TC and Metavir activity score and between higher TG and TC and steatosis. In multivariate analysis, severe hepatitis activity, milder hepatic fibrosis, and triglyceride levels are associated with higher HCV RNA levels.Conclusion. HCV-4 is associated with wide metabolic changes. A proportional relationship is found between serum lipid profiles and hepatitis C viral load and liver histology in patients with HCV-4.