Micropore Closure Rates following Microneedle Application at Various Anatomical Sites in Healthy Human Subjects

2021 ◽  
pp. 1-15
Author(s):  
Abayomi Tolulope Ogunjimi ◽  
Christine Lawson ◽  
Jamie Carr ◽  
Krishna Kumar Patel ◽  
Nkanyezi Ferguson ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Half Life ◽  
Human Subjects ◽  
Transepidermal Water Loss ◽  
Skin Impedance ◽  
Anatomical Site ◽  
Upper Arm ◽  
Healthy Human ◽  
Closure Time ◽  
Volar Forearm

<b><i>Introduction:</i></b> The continuous availability of open micropores is crucial for a successful microneedle (MN) drug delivery strategy. However, micropore lifetime depends on intrinsic skin functional and anatomical characteristics, which vary significantly at different anatomical sites. <b><i>Objective:</i></b> This pilot study explored if differences exist in micropore closure timeframes at 3 anatomical sites – upper arm, volar forearm, and abdomen. <b><i>Methods:</i></b> Healthy subjects (<i>n</i> = 35) self-identifying as Asian (<i>n</i> = 9), Bi-/multiracial (<i>n</i> = 2), Black (<i>n</i> = 9), Latino (<i>n</i> = 6), and White (<i>n</i> = 9) completed the study. The upper arm, volar forearm, and abdomen were treated with MNs; skin impedance and transepidermal water loss (TEWL) were measured at baseline and post-MN to confirm micropore formation. Impedance was measured for 3 days to evaluate micropore lifetime. Measurements of L*, which quantifies the skin lightness/darkness, were made using a tristimulus colorimeter. Micropore lifetime was determined by comparing baseline and post-MN impedance measurements, and micropore closure half-life was predicted using mathematical modeling. <b><i>Results:</i></b> Post-MN increase in TEWL and decrease in impedance were significant (<i>p</i> &#x3c; 0.05), confirming successful micropore formation at all anatomical sites. When data were analyzed according to subject self-identified racial/ethnic groups, the mean micropore closure time at the abdomen (63.09 ± 13.13 h) was longer than the upper arm (60.34 ± 14.69 h) and volar forearm (58.29 ± 16.76 h). The predicted micropore closure half-life at anatomical sites was the abdomen (25.86 ± 14.96 h) ≈ upper arm (23.69 ± 13.67 h) &#x3e; volar forearm (20.2 ± 11.99 h). Differences were not statistically significant between groups. Objective categorization by L* showed that the darker skin may be associated with longer micropore closure time at the abdomen site. <b><i>Conclusions:</i></b> Our results suggest that anatomical site of application may not be a source of significant variability in micropore closure time. These findings may help reduce the number of physiological parameters that need to be explicitly considered when developing drug products to support MN-assisted drug delivery strategies.

scholarly journals Micropore closure time is longer following microneedle application to skin of color

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Abayomi T. Ogunjimi ◽  
Jamie Carr ◽  
Christine Lawson ◽  
Nkanyezi Ferguson ◽  
Nicole K. Brogden
Keyword(s):  
Native American ◽  
Skin Color ◽  
Human Subjects ◽  
Transepidermal Water Loss ◽  
Tristimulus Colorimetry ◽  
Drug Diffusion ◽  
Closure Time ◽  
Race Ethnicity ◽  
Objectively Measured ◽  
First Time

Abstract Microneedles (MNs) allow transdermal delivery of skin-impermeable drugs by creating transient epidermal micropores, and micropore lifetime directly affects drug diffusion timeframes. Healthy subjects (n = 111) completed the study, self-identifying as Asian (n = 32), Bi-/multi-racial (n = 10), Black (n = 22), White (n = 23), Latino (n = 23), and Native American/Hawaiian (n = 1). L* was measured with tristimulus colorimetry to objectively describe skin lightness/darkness. MNs were applied to the upper arm; impedance and transepidermal water loss (TEWL) were measured at baseline and post-MN to confirm micropore formation. Impedance was repeated for 4 days to determine micropore lifetime. Post-MN changes in TEWL and impedance were significant in all groups (p < 0.05), confirming micropore formation regardless of skin type. Micropore lifetime was significantly longer in Blacks (66.5 ± 19.5 h) versus Asians (44.1 ± 14.0 h), Bi-/multi-racial (48.0 ± 16.0 h), and Whites (50.2 ± 2.6 h). Latinos (61.1 ± 16.1 h) had significantly longer micropore closure time versus Asians (44.1 ± 14.0 h). When categorizing data according to L*, micropore lifetime was significantly longer in darker skin. We report for the first time that micropore lifetime differences are present in human subjects of different ethnic/racial backgrounds, with longer micropore lifetime in skin of color. These results also suggest that objectively measured skin color is a better predictor of micropore lifetime than self-identified race/ethnicity.

Abstract 353: Characterization Of Human Plasma Proteome Dynamics Using Deuterium Oxide

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Ding Wang ◽  
David A Liem ◽  
Edward Lau ◽  
Dominic C Ng ◽  
Brian J Bleakley ◽  
...  
Keyword(s):  
Human Plasma ◽  
Protein Turnover ◽  
Half Life ◽  
Human Subjects ◽  
Deuterium Oxide ◽  
Theoretical Method ◽  
Body Water ◽  
Healthy Human ◽  
Critical Determinant ◽  
Disease Mechanisms

Protein turnover half-life is a critical determinant of cardiac homeostasis and can reveal previously unknown disease mechanisms. We recently developed a theoretical method to quantify protein half-life in human using stable isotopes in deuterium oxide (D 2 O). Our goal in the present study is to demonstrate the immediate clinical translation potential of the method by evaluating its safety, feasibility, efficacy, and reproducibility in 10 healthy human subjects. The enrolled human subjects (4 females/6 males; age 22 - 51 y/o; body weight 51 - 108 kg) were labeled with a tailored protocol (UCLA IRB#12-000899), wherein each subject orally consumed weight-adjusted doses of (~45 mL each) 70% D 2 O daily for 14 days to enrich body water and proteins with deuterium. Throughout labeling, the subjects maintained regular food and fluid intake, and normal daily activities. Vital signs and medical health questionnaires were taken daily till 14 days post-labeling. We followed long-term physical conditions and the physiological clearance of D 2 O from body water for up to 240 days post-labeling, finding no physiological effects or signs of discomfort. To monitor label enrichment and post-labeling clearance in the subjects, we measured the D 2 O level of plasma and saliva samples with GC-MS. Both body fluids were reliable sources for monitoring label enrichment kinetics, giving consistent values of individual enrichment levels (0.9-2.2%) and rates (0.15-0.40 d −1 ) in all subjects. Post-labeling D 2 O level naturally subsided with a characteristic half-life of ~7 days (0.1 d −1 ). With LC-MS and the in-house informatics platform Proturn, we successfully characterized the turnover dynamics of >600 human plasma proteins, the largest such human dataset to-date. We detected diverse protein half-life in plasma, e.g., from albumin (18.3 d) to IGF2 (8 h). Importantly, the method can quantify protein half-life with only a single time point, suggesting it can be used to study the dynamics of one single cardiac biopsy (e.g., during heart transplant). In summary, D 2 O labeling is a safe, accessible, and effective technique for widespread clinical investigations of protein turnover dynamics. We further discuss its implications in understanding cardiac disease mechanisms.

scholarly journals Oral Intake of Glucosylceramide Improves Relatively Higher Level of Transepidermal Water Loss in Mice and Healthy Human Subjects

2008 ◽  
Vol 54 (5) ◽  
pp. 559-566 ◽  
Author(s):  
Taro Uchiyama ◽  
Yusuke Nakano ◽  
Osamu Ueda ◽  
Hiroshi Mori ◽  
Masaya Nakashima ◽  
...  
Keyword(s):  
Water Loss ◽  
Human Subjects ◽  
Oral Intake ◽  
Transepidermal Water Loss ◽  
Healthy Human ◽  
Healthy Human Subjects

DES-AA Fibrin Clearance In Healthy Human Subjects

1981 ◽  
Author(s):  
F Brosstad ◽  
T Harrbora ◽  
B Holm ◽  
H C Godal ◽  
P Kierulf
Keyword(s):  
Half Life ◽  
Human Subjects ◽  
Total Radioactivity ◽  
Test Subject ◽  
Healthy Human ◽  
Individual Molecular Species ◽  
Edta Plasma ◽  
Specific Receptors ◽  
The Individual ◽  
Decay Parameters

Plasma clearance of I125 des-AA fibrin mcncmers was studied in healthy subjects (N=7). Labelled mcnaners (fm), made fran labelled fibrinogen (F) in 2,5 M urea, pH 7,4 exposed to insoluble reptilase (Brosstad et al., Thrarto .Res. 13, 1978) vere solubilized upon addition to test-subject plasma, and subsequently injected. At intervals, citrated plasma samples ware tested for: I. Total radioactivity (Tr). II. Radioprecipitability (Rp) with trichloroacetic acid. III. Radioclottability (Rc) with plasmin-free thrcmbin (pH 6,3 1h). IV. Radiodistribution after ultrasentrifuga-ticn (Airfug, Beckmann) and V. Radiodistributicn in SDS-PAGE gels after electrophoresis of harvested EDTA-plasma clots, solubilized in urea-SDS.RESULTS: Prior to injection, plasma demonstrated: Rp = 100 %, Rc = 94 %, single peak ultracentrifuge pattern and 95 % of total radioactivity moving as F on SDS-gels. Almost identical results were obtained in all subjects. After 30 min., Tr had dropped to 50 % of Tr value at 5 min., being 10 % and 2 % after 420 min. and 48 h., correspondingly. A parallell drop in Rp and Rc scarcely noticeable at 10 min., reached a mininun of 30 % at 360 min; the Airfug and SDS-gel patterns substantiating these findings. Due to non-linearity on semilog. plots, a definite half-life of des-AA fibrin cannot be stated from decay parameters (Tr) alone, but metabolic data as outlined above (Rp, Rc, Airfug, SDS-elpho) suggest a half-life of 30-60 min .. In five subjects, I131-des-AA fibrin and I125-fibrinogen was injected simultaneously. Clearance rates characteristic of that of the individual molecular species were obtained. The extremely rapid elimination of fibrin ccnpared to that of fibrinogen suggests specific receptors on RES- cells to be involved.

Minimizing Carry-Over Effects After Treatment Failure and Maximizing Therapeutic Outcome

2014 ◽  
Vol 222 (3) ◽  
pp. 171-178 ◽  
Author(s):  
Mareile Hofmann ◽  
Nathalie Wrobel ◽  
Simon Kessner ◽  
Ulrike Bingel
Keyword(s):  
Treatment Failure ◽  
Human Subjects ◽  
Subsequent Treatment ◽  
Clinical Samples ◽  
Administration Route ◽  
Healthy Human ◽  
Negative Experiences ◽  
Analgesic Treatment ◽  
Balanced Design ◽  
Carry Over

According to experimental and clinical evidence, the experiences of previous treatments are carried over to different therapeutic approaches and impair the outcome of subsequent treatments. In this behavioral pilot study we used a change in administration route to investigate whether the effect of prior treatment experience on a subsequent treatment depends on the similarity of both treatments. We experimentally induced positive or negative experiences with a topical analgesic treatment in two groups of healthy human subjects. Subsequently, we compared responses to a second, unrelated and systemic analgesic treatment between both the positive and negative group. We found that there was no difference in the analgesic response to the second treatment between the two groups. Our data indicate that a change in administration route might reduce the influence of treatment history and therefore be a way to reduce negative carry-over effects after treatment failure. Future studies will have to validate these findings in a fully balanced design including larger, clinical samples.

Detection of Soluble Fibrin Monomer Complexes in Blood by Means of Protamine Sulphate Test

1968 ◽  
Vol 20 (01/02) ◽  
pp. 044-049 ◽  
Author(s):  
B Lipiński ◽  
K Worowski
Keyword(s):  
Human Subjects ◽  
Coronary Thrombosis ◽  
Mean Value ◽  
Healthy Human ◽  
Protamine Sulphate ◽  
Soluble Fibrin ◽  
Fibrin Monomer ◽  
Dog Plasma ◽  
The Mean ◽  
Precipitable Protein

SummaryIn the present paper described is a simple test for detecting soluble fibrin monomer complexes (SFMC) in blood. The test consists in mixing 1% protamine sulphate with diluted oxalated plasma or serum and reading the optical density at 6190 Å. In experiments with dog plasma, enriched with soluble fibrin complexes, it was shown that OD read in PS test is proportional to the amount of fibrin recovered from the precipitate. It was found that SFMC level in plasma increases in rabbits infused intravenously with thrombin and decreases after injection of plasmin with streptokinase. In both cases PS precipitable protein in serum is elevated indicating enhanced fibrinolysis. In healthy human subjects the mean value of OD readings in plasma and sera were found to be 0.30 and 0.11, while in patients with coronary thrombosis they are 0.64 and 0.05 respectively. The origin of SFMC in circulation under physiological and pathological conditions is discussed.

Chronic stress decreases circulating endocannabinoid 2-arachidonoylglycerol in healthy human subjects

2015 ◽  
Author(s):  
Buqing Yi ◽  
Igor Nichiporuk ◽  
Matthias Feuerecker ◽  
Gustav Schelling ◽  
Alexander Chouker
Keyword(s):  
Chronic Stress ◽  
Human Subjects ◽  
Healthy Human ◽  
Healthy Human Subjects

scholarly journals Integration of 3D Printed Flexible Pressure Sensors into Physical Interfaces for Wearable Robots

Sensors ◽  
2021 ◽  
Vol 21 (6) ◽  
pp. 2157
Author(s):  
Kevin Langlois ◽  
Ellen Roels ◽  
Gabriël Van De Velde ◽  
Cláudia Espadinha ◽  
Christopher Van Vlerken ◽  
...  
Keyword(s):  
Pressure Distribution ◽  
Human Subjects ◽  
Pressure Sensors ◽  
Poor Performance ◽  
Capacitive Pressure Sensor ◽  
Upper Arm ◽  
Seamless Integration ◽  
Dynamic Task ◽  
Wearable Robots ◽  
3D Printed

Sensing pressure at the physical interface between the robot and the human has important implications for wearable robots. On the one hand, monitoring pressure distribution can give valuable benefits on the aspects of comfortability and safety of such devices. Additionally, on the other hand, they can be used as a rich sensory input to high level interaction controllers. However, a problem is that the commercial availability of this technology is mostly limited to either low-cost solutions with poor performance or expensive options, limiting the possibilities for iterative designs. As an alternative, in this manuscript we present a three-dimensional (3D) printed flexible capacitive pressure sensor that allows seamless integration for wearable robotic applications. The sensors are manufactured using additive manufacturing techniques, which provides benefits in terms of versatility of design and implementation. In this study, a characterization of the 3D printed sensors in a test-bench is presented after which the sensors are integrated in an upper arm interface. A human-in-the-loop calibration of the sensors is then shown, allowing to estimate the external force and pressure distribution that is acting on the upper arm of seven human subjects while performing a dynamic task. The validation of the method is achieved by means of a collaborative robot for precise force interaction measurements. The results indicate that the proposed sensors are a potential solution for further implementation in human–robot interfaces.

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