Effects of Temperature and Humidity on the Skin Permeation of Hydrophilic and Hydrophobic Drugs.

The humidity was a well-known method to hydrate the skin; however, the published data were varied, and systemic experiments in the previous papers were few. Therefore, the in vitro permeation of excised porcine ear skin by drugs with different polarities [aminopyrine (AMP), antipyrine (ANP), methylparaben (MP), and ibuprofen (IP)] was analyzed under a constant skin surface temperature with different temperatures and humidities to reveal the effects of temperature and humidity on the skin permeation enhancement effects. Applied formulations were prepared by mixing the drug and a hydrophilic vehicle containing glycerin. The disposition-distance profiles of water and the humectant glycerin in the stratum corneum were also investigated using confocal Raman microscopy. High absolute humidity (AH) significantly contributed to the high skin penetration of the hydrophilic penetrants AMP, ANP, and MP but not the hydrophobic penetrant IP. An increase in the partition parameter and a decrease in the diffusivity parameter occurred with an increase in AH, independent of drug polarity. Moreover, we found that dew condensation induced by high AH on temperature-controlled skin surface may effectively increase water content and may provide higher glycerin distribution in the skin barrier, the stratum corneum. Increasing the amount of water and hydrophilic vehicles such as glycerin in the stratum corneum may enhance the permeation of hydrophilic penetrants AMP, ANP, and MP. These data suggested a dew condensation on the skin surface induced by high AH at a constant skin surface temperature would be important to enhance hydrophilic penetrants.

The effect of the chain length distribution of free fatty acids on the mixing properties of stratum corneum model membranes.

The stratum corneum (SC) plays a fundamental role in the barrier function of the skin. The SC consists of corneocytes embedded in a lipid matrix. The main lipid classes in the lipid matrix are ceramides (CERs), cholesterol (CHOL) and free fatty acids (FFAs). The aim of this study was to examine the effect of the chain length of FFAs on the thermotropic phase behavior and mixing properties of SC lipids. Fourier transform infrared spectroscopy and Raman imaging spectroscopy were used to study the mixing properties using either protonated or deuterated FFAs. We selected SC model lipid mixtures containing only a single CER, CHOL and either a single FFA or a mixture of FFAs mimicking the FFA SC composition. The single CER consists of a sphingoid base with 18 carbon atoms and an acyl chain with a chain length of 24 carbon atoms. When using lignoceric acid (24 carbon atoms) or a mixture of FFAs, the CER and FFAs participated in mixed crystals, but hydration of the mixtures induced a slight phase separation between CER and FFA. The mixed crystalline structures did not phase separate during storage even up to a time period of 3months. When using palmitic acid (16 carbon atoms), a slight phase separation was observed between FFA and CER. This phase separation was clearly enhanced during hydration and storage. In conclusion, the thermotropic phase behavior and the mixing properties of the SC lipid mixtures were shown to strongly depend on the chain length and chain length distribution of FFAs, while hydration enhanced the phase separation.

Observation and density estimation of a large number of skin capillaries using wide-field portable video capillaroscopy and semantic segmentation.

Significance: Skin capillaries are non-invasively observable; their structure and blood flow can reflect tissue and systemic conditions. Quantitative analysis of video-capillaroscopy images yields novel diagnostic methods. Because the capillary structure is heterogeneous, analyzing more capillaries can increase the evaluation reliability. Aim: We developed a system that can observe and quantify numerous capillaries and verified the performance on human skin. Approach: We developed a portable video-capillaroscope with a spatial resolution higher than 3.5 µm and a wide field of view (7.4 mm×5.5 mm) and a method to evaluate capillary numbers and areas using U-Net. The model was trained and tested with 22 and 11 cropped images (2.4 mm×1.9 mm) obtained from 11 participants, respectively. They were then applied to the 7.2 mm×5.3 mm images from four participants. Segmentation results were compared to ground-truth at the pixel level and capillary-region level. Results: Over 1000 capillaries were simultaneously observed using the proposed system. Although pixel-level segmentation performance was low [intersection over union (IoU) = 24.5%], the number and area could be estimated. These values differed among four participants and seven sites, and they changed after skin barrier destruction. Conclusions: The proposed system allows for observing and quantifying numerous skin capillaries simultaneously, suggesting its potential for evaluating tissue and systemic conditions.

Three-dimensional gait analysis of the effect of directional steering on gait in patients with Parkinson's disease.

INTRODUCTION: Deep Brain Stimulation (DBS) is an option to treat advanced Parkinson's Disease (PD), but can cause gait disturbance due to stimulation side efffects. This study aims to evaluate the objective effect of directional current steering by DBS on gait performance in PD, utilizing a three-dimensional gait analysis system. METHODS: Eleven patients diagnosed with PD and were implanted with directional lead were recruited. The direction of the pyramidal tract (identified by the directional mode screening) was set as 0°. Patients performed the six-meter-walk test and the time up-and-go (TUG) test while an analysis system recorded gait parameters utilizing a three-dimensional motion capture camera. The gait parameters were measured for the baseline, the directional steering at eight angles (0°, 45°, 90°, 135°, 180°, 225°, 270°, and 315°), and the conventional ring mode with 1, 2, and 3 mA. Pulse width and frequency were fixed. Placebo stimulation (0 mA) was used for a control. RESULTS: Eleven patients completed the study. No significant difference were observed between gait parameters during the directional, baseline, placebo, or ring modes during the six-meter-walk test (p > 0.05). During the TUG test, stride length was significantly different between 0° and other directions (p < 0.001), but no significant differences were observed for the other gait parameters. Stride width was non-significantly narrower in the direction of 0°. CONCLUSION: Controlling stimulation using directional steering may improve gait in patients with PD, while avoiding pyramidal side effects.

Assessment of Multidimensional Health Care Parameters Among Adults in Japan for Developing a Virtual Human Generative Model: Protocol for a Cross-sectional Study.

BACKGROUND: Human health status can be measured on the basis of many different parameters. Statistical relationships among these different health parameters will enable several possible health care applications and an approximation of the current health status of individuals, which will allow for more personalized and preventive health care by informing the potential risks and developing personalized interventions. Furthermore, a better understanding of the modifiable risk factors related to lifestyle, diet, and physical activity will facilitate the design of optimal treatment approaches for individuals. OBJECTIVE: This study aims to provide a high-dimensional, cross-sectional data set of comprehensive health care information to construct a combined statistical model as a single joint probability distribution and enable further studies on individual relationships among the multidimensional data obtained. METHODS: In this cross-sectional observational study, data were collected from a population of 1000 adult men and women (aged ≥20 years) matching the age ratio of the typical adult Japanese population. Data include biochemical and metabolic profiles from blood, urine, saliva, and oral glucose tolerance tests; bacterial profiles from feces, facial skin, scalp skin, and saliva; messenger RNA, proteome, and metabolite analyses of facial and scalp skin surface lipids; lifestyle surveys and questionnaires; physical, motor, cognitive, and vascular function analyses; alopecia analysis; and comprehensive analyses of body odor components. Statistical analyses will be performed in 2 modes: one to train a joint probability distribution by combining a commercially available health care data set containing large amounts of relatively low-dimensional data with the cross-sectional data set described in this paper and another to individually investigate the relationships among the variables obtained in this study. RESULTS: Recruitment for this study started in October 2021 and ended in February 2022, with a total of 997 participants enrolled. The collected data will be used to build a joint probability distribution called a Virtual Human Generative Model. Both the model and the collected data are expected to provide information on the relationships between various health statuses. CONCLUSIONS: As different degrees of health status correlations are expected to differentially affect individual health status, this study will contribute to the development of empirically justified interventions based on the population. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/47024.

Treatment with Synthetic Pseudoceramide Improves Atopic Skin, Switching the Ceramide Profile to a Healthy Skin Phenotype.

Little is known about the pathophysiological linkages between altered ceramide profiles in the stratum corneum (SC) of patients with atopic dermatitis and their impaired skin barrier and water-holding functions. We studied those characteristics following topical treatment with a designed synthetic pseudoceramide (pCer) and analyzed that pathophysiological linkage by microanalyzing ceramides using normal phase liquid chromatography-electrospray ionization mass spectrometry. Four weeks of treatment with pCer significantly reduced skin symptoms, accompanied by significant decreases in transepidermal water loss and increases in water content. In the SC ceramide profiles, ceramides containing nonhydroxy fatty acids and 6-hydroxysphingosines (Cer[NH]) and ceramides containing nonhydroxy fatty acids and phytosphingosines (Cer[NP]) increased, whereas ceramides containing nonhydroxy fatty acids and sphingosines (Cer[NS]) and ceramides containing a-hydroxy fatty acids and sphingosines (Cer[AS]) decreased, with larger alkyl chain lengths in Cer[NS], distinctly representing a switch from an atopic dermatitis to a healthy skin phenotype. The level of pCer that penetrated into the SC was significantly correlated with the SC water content but not with transepidermal water loss. The level and the average carbon chain length of Cer[NS] were closely correlated with the pCer level in the SC. These findings indicate that the penetrated pCer contributes to shift the ceramide profile from an atopic dermatitis to a healthy skin phenotype. Taken together, the observed clinical efficacy of treatment with pCer provides a deep insight into the pathogenesis of atopic dermatitis as a ceramide-deficient disease.

Surfactant uptake dynamics in mammalian cells elucidated with quantitative coherent anti-stokes Raman scattering microspectroscopy.

The mechanism of surfactant-induced cell lysis has been studied with quantitative coherent anti-Stokes Raman scattering (CARS) microspectroscopy. The dynamics of surfactant molecules as well as intracellular biomolecules in living Chinese Hamster Lung (CHL) cells has been examined for a low surfactant concentration (0.01 w%). By using an isotope labeled surfactant having CD bonds, surfactant uptake dynamics in living cells has been traced in detail. The simultaneous CARS imaging of the cell itself and the internalized surfactant has shown that the surfactant molecules is first accumulated inside a CHL cell followed by a sudden leak of cytosolic components such as proteins to the outside of the cell. This finding indicates that surfactant uptake occurs prior to the cell lysis, contrary to what has been believed: surface adsorption of surfactant molecules has been thought to occur first with subsequent disruption of cell membranes. Quantitative CARS microspectroscopy enables us to determine the molecular concentration of the surfactant molecules accumulated in a cell. We have also investigated the effect of a drug, nocodazole, on the surfactant uptake dynamics. As a result of the inhibition of tubulin polymerization by nocodazole, the surfactant uptake rate is significantly lowered. This fact suggests that intracellular membrane trafficking contributes to the surfactant uptake mechanism.

Protein secondary structure imaging with ultrabroadband multiplex coherent anti-Stokes Raman scattering (CARS) microspectroscopy.

Protein secondary structures in human hair have been studied with ultrabroadband multiplex coherent anti-Stokes Raman scattering (CARS) microspectroscopy. The CARS peak-shift mapping method has been developed and applied to hair samples with and without treatments by chemical reduction and mechanical extension. It clearly visualizes the treatment induced changes in protein secondary structures and their spatial distributions. Using the new imaging technique, we found a multilayered structure in the human hair cortex.

Infrared photodissociation spectroscopy of protonated ammonia cluster ions, NH4+(NH3)n (n=5-8), by using infrared free electron laser.

Infrared photodissociation action spectra of protonated ammonia cluster ions, NH(4) (+)(NH(3))(n) (n=5-8), were measured in the range of 1020-1210 cm(-1) by using a tunable infrared free electron laser. Analyses by the density functional theory (DFT) show that the spectral features observed can be assigned to the nu(2) vibrational mode of the NH(3) molecules in NH(4) (+)(NH(3))(n). Size dependence of the spectra supports structural models obtained by the DFT calculations, in which the NH(4) (+) ion is solvated by the four nearest-neighbor NH(3) molecules. For NH(4) (+)(NH(3))(5), the spectrum between 1000 and 1700 cm(-1) was measured. The nu(4) bands of the NH(3) molecules and the NH(4) (+) ion were found in the range of 1420-1700 cm(-1).