Imaging and Analysis of Human Vocal Fold Vibration Using Two-Dimensional (2D) Scanning Videokymography.

OBJECTIVE: Laryngeal videokymography and high-speed digital kymography are the currently available techniques for studying aperiodic vibration of the vocal folds. However, videokymography has a fundamental limitation that only linear portions of the vocal fold mucosa can be visualized, whereas high-speed digital kymography has the disadvantages of lack of immediate feedback during examination and considerable waiting time before kymographic visualization. We developed a new system, two-dimensional (2D) scanning videokymography, that provides a possible alternative for evaluation of the vibratory pattern of the vocal folds. Herein, we report the application of 2D scanning videokymography for visualization of vocal fold vibration in humans and an analysis of its parameters. MATERIALS AND METHODS: Two young healthy volunteers (one man and one woman) took part in this study. The vibratory patterns of their vocal folds were evaluated using 2D scanning videokymography and laryngeal stroboscopy. RESULTS: Two-dimensional scanning videokymography provided a high-definition image of the vibratory movements of the vocal folds. In analysis of the images acquired by the device, various parameters including fundamental frequency; ratio of the vibratory phases; phase, amplitude, and glottal area symmetry; and cycle-to-cycle variability were extracted. CONCLUSIONS: Our results indicate that 2D scanning videokymography is a useful and promising tool for visualization of the vibratory movement of the vocal folds. This new technique might improve our understanding of the mechanism of vocal fold vibration and contribute to voice research as well as clinical practice.

Titanium dioxide inclusion in backing reduce the photoallergenicity of ketoprofen transdermal patch.

Ketoprofen (KP) is a widely used transdermal non-steroidal anti-inflammatory drug. However, increasing number of adverse effect case reports suggests that KP transdermal formulation can cause photoallergic reaction. The photoallergic potential of KP is attributable to the instability of KP under UV/visible light and subsequent formation of reactive degradation products. In this study, we investigated whether the inclusion of titanium dioxide (TiO(2)), a well-known mineral sunscreen agent, in the KP transdermal patch can prevent the photodegradation of KP and ultimately, can reduce photoallergic reaction. TiO(2) inclusion in fabric backing effectively decreased the UV transmission through fabric patch throughout all UVA region from 320 to 380 nm and consistently, KP patch with TiO(2) exhibited significantly increased photostability of KP. This enhanced photostability of KP resulted in reduced generation of photodegradation product as determined by HPLC-UV analysis. In a good accordance with these in vitro results, photosensitization test in guinea pig in vivo demonstrated low photoallergic reactions of KP patch with TiO(2) compared to KP patch without TiO(2), indeed. This study demonstrated that KP transdermal patch with TiO(2)-included backing can provide with improved photostability and photosafety over conventional fabric KP patch.

The fatty acid conjugated exendin-4 analogs for type 2 antidiabetic therapeutics.

Improved glucagon-like peptide-1 (GLP-1) receptor activation is considered one of the most effective targets for antidiabetic therapy. For this purpose, we modified the GLP-1 analog of exendin-4 using two fatty acids (FA) either lauric acid (LUA, C12) or palmitic acid (PAA, C16) at its two lysine residues, to produce; Lys(12)-FA-Exendin-4 (FA-M2), Lys(27)-FA-Exendin-4 (FA-M1), or Lys(12,27)-diBA-Exendin-4 (FA-Di). The structural, biological, and pharmaceutical characteristics of these exendin-4 analogs were then investigated. Biological activity tests demonstrated that LUA-M1 had well-preserved in vivo antidiabetic activity and in vitro insulinotropic activity with minimum GLP-1 receptor binding affinity loss as compared with exendin-4. Furthermore, pharmacokinetic studies in rats revealed that s.c. administration of LUA-M1 significantly enhanced pharmacokinetic parameters, such as, elimination half-life, mean residence time, and AUC values as compared with exendin-4. The protracted antidiabetic effects of LUA-M1 were also confirmed by prolonged normoglycemia observed in type 2 diabetic mice (20nmol/mouse single injection of exendin-4 or LUA-M1 induced normoglycemia for 6 or 24h, respectively). These findings suggest that FA conjugated exendin-4s should be considered potential candidates for the treatment of diabetes.

Preparation and structural, biochemical, and pharmaceutical characterizations of bile acid-modified long-acting exendin-4 derivatives.

To develop an effective long-acting antidiabetic, the GLP-1 analogue of exendin-4 was modified with three different bile acids (BAs; cholic, deoxycholic, or lithocholic acid), at its two lysine residues. The biological, pharmaceutical, and physicochemical characteristics of these exendin-4 analogues were carefully investigated. Biological activity tests demonstrated that the monobile acid substitutions of exendin-4 showed well preserved receptor binding efficacy without noticeable insulinotropic or antidiabetic activity loss. However, physicochemical and pharmacokinetic studies revealed that the albumin-binding properties and in vivo elimination half-lives of BAM1-Ex4s (Lys(27)-BA-Ex4s) were significantly enhanced by increasing the hydrophobicities of the conjugated BAs. Furthermore, the protracted antidiabetic effects of the BAM1-Ex4s were also verified by the prolonged restoration of normoglycemia in type 2 diabetic mice. Accordingly, the present study suggests that the derivatization of exendin-4 with BAs offers a means of producing long-acting GLP-1 receptor agonists for type 2 diabetic therapy.

Pharmacokinetics and pharmacodynamics of ketoprofen plasters.

Ketoprofen plasters of 70 cm(2) size using DuroTak acrylic adhesive polymers were developed either containing 30 mg (Ketotop-L) or 60 mg drug (Ketotop-P). The in vitro skin permeation profile was obtained in hairless mouse skin and showed the permeation rate of Ketotop-P to be twice that of Ketotop-L. The plasma concentration profile of ketoprofen was determined in Sprague-Dawley rats after applying a 3 x 3 cm(2) plaster. AUC(0-24h) and C(max) of Ketotop-P were 260.92 microg.h/ml and 25.09 microg/ml, respectively, which were about twice the values of Ketotop-L. The hind paw edema induced by carrageenan injection was measured for 6 h after applying a 2 x 2 cm(2) plaster, and the area under the time-response curve (AUR) value was significantly lower in Ketotop-P attached rats (180.70%.h) than in those with the Ketotop-L (298.65%.h) and the control (407.04%.h) groups, indicating a stronger anti-inflammatory action of Ketotop-P. However, the analgesic effect of the two formulations did not show a statistically significant difference. In conclusion, Ketotop-P was able to achieve higher plasma concentration of ketoprofen, thereby exhibiting higher and more constant anti-inflammatory effect compared with Ketotop-L.

Ketoprofen: experimental overview of dermal toxicity.

Ketoprofen (KP) is a widely used non-steroidal anti-inflammatory drug (NSAID). However, an increasing number of case reports suggest that in broad use, KP can cause allergic dermatitis. Most of these adverse effects have been attributed to the photoallergic potential of KP and photosensitivity. With the exception of a few reports in experimental animals, there is little evidence that KP actually causes dermal toxicity. In this study, in order to investigate the eventual underlying causes of KP dermal toxicity, we conducted primary irritation, skin cumulative, skin sensitization, phototoxicity and photosensitization tests in rodents and rabbits. Primary irritation and skin cumulative testing using New Zealand white rabbits revealed that application of KP (22, 15 and 10%) did not induce erythema or edema formation. Moreover, in skin sensitization and skin phototoxicity testing, using Hartley albino guinea pigs, there was no evidence of allergic or phototoxic potential. In the photosensitization test, KP induced skin reactions in six of eight guinea pigs with signs of erythema on the application site. Histologically, in photosensitized skin, epidermal hyperplasia, including incremental stratum granulosum, acanthosis, keratinocyte hypertrophy and dermal inflammatory cell infiltration, was observed. In this animal study, no primary irritation, cumulative irritation, skin sensitization or skin phototoxicity was observed with KP treatment. However, we identified photosensitization as the underlying cause of KP dermal toxicity.