Modelling and Control of Corticotropin Permeation from Hydrogels across a Natural Membrane in the Presence of Albumin

(1) Background: Skin is a difficult barrier to overcome, especially for molecules with masses greater than 500 Da. It has been suggested that albumin may contribute to more effective penetration of many therapeutic substances. In this study, an attempt was made to use albumin in semi-solid formulations to increase the skin penetration of another peptide—corticotropin (ACTH). (2) Methods: Hydrogels were prepared at two concentrations: 15 mg/g and 20 mg/g corticotropin, then albumin was added to them in different stoichiometric ratios. The degree of ACTH release from hydrogels, both with and without albumin addition, was investigated. For selected hydrogels the process of corticotropin permeation through a model membrane, i.e., pig skin, was examined. (3) Results: The study of corticotropin release showed that the addition of albumin, depending on its amount, may delay or increase the release process. Similarly, a study of ACTH permeation through porcine skin showed that albumin can delay or increase and accelerate ACTH permeation. (4) Conclusions: Hydrogel, applicated on the skin surface, may prove to be a beneficial and convenient solution for patients. It is an innovative way of application ACTH that bypasses the gastrointestinal tract and may result in increased availability of the peptide and its efficacy.

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A Laboratory Method to Measure Skin Surface Staining by Cigarette Smoke, Tobacco Heating Products and E-Cigarettes

Contributions to Tobacco & Nicotine Research ◽

10.2478/cttr-2021-0013 ◽

2021 ◽

Vol 30 (4) ◽

pp. 158-166

Author(s):

Annette Dalrymple ◽

Emma-Jayne Bean ◽

Jesse Thissen ◽

Holger Behrsing ◽

Steven Coburn ◽

...

Keyword(s):

Cigarette Smoke ◽

Skin Surface ◽

Laboratory Method ◽

Porcine Skin ◽

Skin Sample ◽

Side Stream ◽

Air Control ◽

And Control ◽

Skin Samples

Summary Exhaled or side-stream cigarette smoke (CS) may visually stain a consumer's skin over time. Tobacco heating products (THPs) and e-cigarettes (ECs) have reduced staining potential because they do not produce side-stream aerosols and their exhaled aerosols have significantly reduced levels of toxicants, particles and odour. Here we assess discolouration of porcine skin in vitro after exposure to particulate matter (PM) or aerosols from CS (3R4F), two THPs (glo and glo sens) and an EC (iSwitch Maxx). PM was prepared by capturing aerosols on Cambridge filter pads and eluting with dimethyl sulfoxide (DMSO). Abattoir-obtained porcine skin samples were incubated with PM or DMSO control at 37 °C between 0 and 6.0 h. For aerosol assessment, porcine skin samples were exposed to between 50 and 400 puffs of the products, or air control, using a smoking machine. Colour profiles and staining levels of each skin sample were measured at different timepoints and puff thresholds using a spectrophotometer. Staining increased with time and dose, the greatest changes being observed following exposure to aerosols and PM from CS. THP, EC and control values were significantly different from CS after 0.5 h exposure to PM or 50 puffs of aerosols. The minimal staining induced by THPs and EC was comparable to controls. These data suggest that THPs and ECs could offer hygiene benefits to consumers who switch from smoking cigarettes. Further studies are required to assess the longer-term effects of THPs and ECs on skin discoloration. [Contrib. Tob. Nicotine Res. 30 (2021) 158–166]

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Candida auris Forms High-Burden Biofilms in Skin Niche Conditions and on Porcine Skin

mSphere ◽

10.1128/msphere.00910-19 ◽

2020 ◽

Vol 5 (1) ◽

Cited By ~ 11

Author(s):

Mark V. Horton ◽

Chad J. Johnson ◽

John F. Kernien ◽

Tarika D. Patel ◽

Brandon C. Lam ◽

...

Keyword(s):

Fungal Pathogen ◽

Hospital Setting ◽

Skin Surface ◽

Skin Model ◽

Porcine Skin ◽

Candida Auris ◽

Content Type ◽

High Burden ◽

Pig Skin ◽

Invasive Infections

The emerging fungal pathogen Candida auris causes invasive infections and is spreading in hospitals worldwide. Why this species exhibits the capacity to transfer efficiently among patients is unknown. Our findings reveal that C. auris forms high-burden biofilms in conditions mimicking sweat on the skin surface. These adherent biofilm communities persist in environmental conditions expected in the hospital setting. Using a pig skin model, we show that C. auris also forms high-burden biofilm structures on the skin surface. Identification of this mode of growth sheds light on how this recently described pathogen persists in hospital settings and spreads among patients.

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Insights into the Control of Drug Release from Complex Immediate Release Formulations

Pharmaceutics ◽

10.3390/pharmaceutics13070933 ◽

2021 ◽

Vol 13 (7) ◽

pp. 933

Author(s):

Runqiao Dong ◽

James C. DiNunzio ◽

Brian P. Regler ◽

Walter Wasylaschuk ◽

Adam Socia ◽

...

Keyword(s):

Drug Release ◽

Immediate Release ◽

Liquid Penetration ◽

Central Importance ◽

Water Penetration ◽

Release Process ◽

Terahertz Pulsed Imaging ◽

And Control ◽

Kinetics Of ◽

Spray Dried

The kinetics of water transport into tablets, and how it can be controlled by the formulation as well as the tablet microstructure, are of central importance in order to design and control the dissolution and drug release process, especially for immediate release tablets. This research employed terahertz pulsed imaging to measure the process of water penetrating through tablets using a flow cell. Tablets were prepared over a range of porosity between 10% to 20%. The formulations consist of two drugs (MK-8408: ruzasvir as a spray dried intermediate, and MK-3682: uprifosbuvir as a crystalline drug substance) and NaCl (0% to 20%) at varying levels of concentrations as well as other excipients. A power-law model is found to fit the liquid penetration exceptionally well (average R2>0.995). For each formulation, the rate of water penetration, extent of swelling and the USP dissolution rate were compared. A factorial analysis then revealed that the tablet porosity was the dominating factor for both liquid penetration and dissolution. NaCl more significantly influenced liquid penetration due to osmotic driving force as well as gelling suppression, but there appears to be little difference when NaCl loading in the formulation increases from 5% to 10%. The level of spray dried intermediate was observed to further limit the release of API in dissolution.

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Evaluation of Melasma Treatment Effectiveness by Skin Biophysical Indices

Bulletin of Science and Practice ◽

10.33619/2414-2948/72/25 ◽

2021 ◽

Vol 7 (11) ◽

pp. 201-209

Keyword(s):

Treatment Effectiveness ◽

Skin Pigmentation ◽

Skin Surface ◽

Control Group ◽

Control Groups ◽

Normal Range ◽

Dry Skin ◽

Biophysical Indicators ◽

And Control ◽

Biophysical Indices

This article presents an assessment of the effectiveness of treatment of melasma according to the biophysical indicators of skin 176 patients who applied to the DIVA EFFECT private cosmetology clinic in Bishkek (Kyrgyzstan) in 2018–2020. The control group included 85 women without facial skin pigmentation. Criteria for inclusion in the study of patients: age 20–60 years, skin pigmentation for 1–12 years, residence in Kyrgyzstan, informed consent and consent to procedures for diagnosis, treatment. Amounts of sebum on skin surface, level of skin moisture and pigmentation, acid-alkaline balance of skin are determined. Despite the lack of sebum in all types of melasma, greater fat content was detected at 20–29 years old, including in the control group. The treatment helped to increase skin humidity, but with different intensities. Treatment slightly increased skin humidity, but only dry skin was characteristic of patients, both in the experimental and control groups. In patients of the control group, skin pH was from 4.1±0.5 to 4.8±0.5. The acid-alkaline balance of the skin in patients was mainly lower than normal, with the exception of the age group of 20–29 years, 30–39 years with dermal melasma. After treatment, the melanin content was within normal range at all types of melasma compared to the control group. The treatment performed reduced skin greasiness in epidermal and dermal type, acid-alkaline skin balance in dermal and mixed type. Melanin levels decreased and skin humidity increased slightly with all types.

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Cephalexin-Induced Stevens-Johnson Syndrome

Annals of Pharmacotherapy ◽

10.1177/106002809202601006 ◽

1992 ◽

Vol 26 (10) ◽

pp. 1230-1233 ◽

Cited By ~ 15

Author(s):

Kim M. Murray ◽

Michael S. Camp

Keyword(s):

Gastrointestinal Tract ◽

Lupus Erythematosus ◽

Skin Surface ◽

Skin Lesions ◽

Infectious Complications ◽

The Body ◽

Stevens Johnson Syndrome ◽

Medline Search ◽

Johnson Syndrome ◽

Macular Rash

OBJECTIVE: To report a case of cephalexin-induced Stevens-Johnson syndrome (SJS), a devastating adverse drug reaction that involves the entire skin surface and mucosal areas of the body. DATA SOURCES: MEDLINE search (key terms cephalosporins, Stevens-Johnson syndrome, erythema multiforme, and systemic lupus erythematosus) and references identified from bibliographies of pertinent articles. DATA SYNTHESIS: Clinical presentation and manifestations of SJS include the skin, eyes, gastrointestinal tract, and pulmonary system. Infectious complications are the leading cause of mortality. Early intervention is important to prevent progression of SJS. The case described is consistent with the features of this syndrome. The patient presented with fever, arthralgias, and malaise. Skin lesions included a diffuse violet macular rash with erythema and multiple bullous lesions on her neck and abdomen. The skin biopsy was consistent with SJS. Multiple mucocutaneous ulcers were found in her mouth, but no evidence of lower gastrointestinal tract involvement was documented. She remained relatively free of pulmonary complaints except for the presenting bronchitis. CONCLUSIONS: Cephalexin should be added to the list of agents to consider as iatrogenic causes of SJS.

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Sonographic Evaluation of Plantar Fasciitis and its Relation to Body Mass Index and Heel Pad Thickness

Nepalese Journal of Radiology ◽

10.3126/njr.v9i2.27427 ◽

2020 ◽

Vol 9 (2) ◽

pp. 32-39

Author(s):

Prashant Khatiwada ◽

Dinesh Chataut ◽

Kamal Subedi

Keyword(s):

Body Mass Index ◽

Body Mass ◽

Plantar Fasciitis ◽

Plantar Fascia ◽

Skin Surface ◽

Control Group ◽

Heel Pad ◽

And Control ◽

Calcaneal Tuberosity ◽

Symptomatic Side

Introduction: To study the sonographic appearance of plantar fascia in clinically suspected cases of plantar fasciitis (PFs) using both quantitative and qualitative parameters, and to establish the correlation between plantar fasciitis, body mass index (BMI) and heel pad thickness (HPT). Methods: In this case controlled analytical study, we sonographically evaluated 100 patients with clinical plantar fasciitis (unilateral: 90, bilateral: 10 with mean age 46.9yrs) and control group of 60 (120 heels) healthy volunteers with mean age 45.3yrs. Plantar Fascia Thickness (PFT), HPT, hypoechogenity, biconvexity, perifascial fluid, intrafascial calcification and subcalcaneal spurs were evaluated sonographically. PFT was measured 5mm distal to the calcaneal insertion of plantar aponeurosis. The unloaded HPT was measured from the skin surface to the nearest calcaneal tuberosity. Results: Mean Plantar Fascia Thickness (PFT) and Heel Pad Thickness (HPT) are greater on the symptomatic side for patients with unilateral and bilateral PFs than on the asymptomatic side for patients with unilateral PFs, and also control subjects (PFT values are 4.41 ± 0.59, 4.63 ± 0.55, 2.83 ± 0.36, 2.62± 0.37 mm, and HPT values 17.64 ± 1.07, 17.28 ± 1.10, 16.91 ± 1.06, 16.73 ± 1.13 mm, respectively) (p <0.0001). Mean BMI values of the case and control groups are 26.14 ± 1.9 and 24.42 ± 0.89 Kg/m2, respectively (p <0.05). We found hypoechogenicity of plantar fascia in 80 cases (72.7%), calcaneal spur in 69 cases (62.7%), biconvexity in 11 cases (10%) and perifascial fluid in 16 cases (14.5%) within the plantar fasciitis group (110 symptomatic heels). Conclusion: Increased plantar fascia thickness, increased heel pad thickness and hypoechogenicity of plantar fascia are consistent sonographic findings in plantar fasciitis. Its occurrence has significant relation to high BMI.

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Effects of pyridoxine deficiency and dl-p-chlorophenylalanine administration to rats on 5-hydroxytryptamine and noradrenaline concentrations in brain and 5-hydroxytryptamine concentration in blood

Biochemical Journal ◽

10.1042/bj1340763 ◽

1973 ◽

Vol 134 (3) ◽

pp. 763-767 ◽

Cited By ~ 4

Author(s):

Hemmige N. Bhagavan ◽

David B. Coursin

Keyword(s):

Body Weight ◽

Gastrointestinal Tract ◽

Tryptophan Hydroxylase ◽

Marked Decrease ◽

Brain Weight ◽

Pyridoxine Deficiency ◽

Weanling Rats ◽

And Control ◽

Rate Limiting ◽

The Brain

Pyridoxine deficiency in post-weanling rats caused a marked decrease in body weight and a small but significant decrease in brain weight. Although the concentration of circulating 5-hydroxytryptamine was markedly decreased, the concentrations of 5-hydroxytryptamine and noradrenaline in the brain were not affected. p-Chlorophenylalanine, an inhibitor of 5-hydroxytryptamine synthesis, decreased the 5-hydroxytryptamine content of brain to very low values in both the deficient and control animals, whereas the noradrenaline contents were not appreciably affected. The concentration of 5-hydroxytryptamine in blood, the origin of which is primarily gastrointestinal, was decreased only in the controls but not in the deficient animals after p-chlorophenylalanine treatment. These results suggest that whereas l-tryptophan hydroxylase (EC 1.14.3.2) is rate-limiting in the brain as has been reported by others, the pyridoxal 5′-phosphate-dependent enzyme 5-hydroxytryptophan decarboxylase (EC 4.1.1.28) may be more important in the gastrointestinal tract in the regulation of 5-hydroxytryptamine synthesis.

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Corticotropin Secretory Dynamics in Humans under Low Glucocorticoid Feedback

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.86.11.8046 ◽

2001 ◽

Vol 86 (11) ◽

pp. 5554-5563 ◽

Cited By ~ 24

Author(s):

J. D. Veldhuis ◽

A. Iranmanesh ◽

D. Naftolowitz ◽

N. Tatham ◽

F. Cassidy ◽

...

Keyword(s):

Negative Feedback ◽

High Dose ◽

Plasma Acth ◽

Acth Secretion ◽

Burst Frequency ◽

Feedback Controls ◽

Release Process ◽

Adrenal Axis ◽

Pituitary Adrenal Axis ◽

Acth Release

To explore the mechanisms of homeostatic adaptation of the hypothalamo-pituitary-adrenal axis to an experimental low-feedback condition, we quantitated pulsatile (ultradian), entropic (pattern-sensitive), and 24-h rhythmic (circadian) ACTH secretion during high-dose metyrapone blockade (2 g orally every 2 h for 12 h, and then 1 g every 2 h for 12 h). Plasma ACTH and cortisol concentrations were sampled concurrently every 10 min for 24 h in nine adults. The metyrapone regimen reduced the amplitude of nyctohemeral cortisol rhythm by 45% (P = 0.0013) and delayed the time of the cortisol maximum (acrophase) by 7.1 h (P = 0.0002). Attenuated cortisol negative feedback stimulated a 7-fold increase in the mean (24-h) plasma ACTH concentration, which rose from 24 ± 1.6 to 169± 31 pg/ml (ng/liter) (P < 0.0001). Augmented ACTH output was driven by a 12-fold amplification of ACTH secretory burst mass (integral of the underlying secretory pulse) (21 ± 3.1 to 255 ± 64 pg/ml; P < 0.0001), yielding a higher percentage of ACTH secreted in pulses (53 ± 3.5 vs. 92 ± 1.3%; P < 0.0001). There were minimal elevations in basal (nonpulsatile) ACTH secretion (by 50%; P = 0.0049) and ACTH secretory burst frequency (by 36%; P = 0.031). The estimated half-life of ACTH (median, 22 min) and the calculated ACTH secretory burst half-duration (pulse event duration at half-maximal amplitude) (median, 23 min) did not change. Hypocortisolemia evoked remarkably more orderly subordinate patterns of serial ACTH release, as quantitated by the approximate entropy statistic (P= 0.003). This finding was explained by enhanced regularity of successive ACTH secretory pulse mass values (P = 0.032). In contrast, there was no alteration in serial ACTH interpulse-interval (waiting-time) regularity. At the level of 24-h ACTH rhythmicity, cortisol withdrawal enhanced the daily rhythm in ACTH secretory burst mass by 29-fold, elevated the mesor by 16-fold, and delayed the acrophase by 3.4 h from 0831 h to 1154 h (each P < 10−3). In summary, short-term glucocorticoid feedback deprivation primarily (>97% of effect) amplifies pulsatile ACTH secretory burst mass, while minimally elevating basal/nonpulsatile ACTH secretion and ACTH pulse frequency. Reduced cortisol feedback paradoxically elicits more orderly (less entropic) patterns of ACTH release due to emergence of more regular ACTH pulse mass sequences. Cortisol withdrawal concurrently heightens the amplitude and mesor of 24-h rhythmic ACTH release and delays the timing of the ACTH acrophase. In contrast, the duration of underlying ACTH secretory episodes is not affected, which indicates that normal pulse termination may be programmed centrally rather than imposed by rapid negative feedback. Accordingly, we hypothesize that adrenal glucocorticoid negative feedback controls hypothalamo-pituitary-adrenal axis dynamics via the 3-fold distinct mechanisms of repressing the mass of ACTH secretory bursts, reducing the orderliness of the corticotrope release process, and modulating the intrinsic diurnal rhythmicity of the hypothalamo-corticotrope unit.

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ULTRASOUND ENHANCED SKIN OPTICAL CLEARING: MICROSTRUCTURAL CHANGES

Journal of Innovative Optical Health Sciences ◽

10.1142/s1793545810000964 ◽

2010 ◽

Vol 03 (03) ◽

pp. 189-194 ◽

Cited By ~ 5

Author(s):

XIANGQUN XU ◽

CHAOJIE SUN

Keyword(s):

Lipid Bilayers ◽

Ex Vivo ◽

Skin Surface ◽

Glycerol Solution ◽

Porcine Skin ◽

Intact Skin ◽

Sem Images ◽

Optical Clearing ◽

Better Than

Our previous studies demonstrated the ultrasound-induced skin optical clearing enhancement with topical application of optical clearing agents on in vitro porcine skin and in vivohuman skin. The objective of this study was to investigate the possible mechanisms of the enhanced skin optical clearing by ultrasound medications. Optical clearing effects of ex vivo guinea pig abdomen skin topically applied with 60% glycerol or the combination of 60% glycerol and ultrasound were studied by optical coherence tomography (OCT). Microstructure of skin surface was examined by scanning electron microscopy (SEM). Ultrasound with a frequency of 1 MHz and a power of 0.75 W over a 3-cm probe was simultaneously applied with glycerol solution for 15 min. The combination of 60% glycerol and ultrasound results in a 19% increase in OCT 1/e light penetration depth after 30 min, which is much better than 60% glycerol alone. SEM images demonstrated that changes in skin microstructure due to the tight order of the lipid bilayers in the stratum corneum disrupted and the separation of keratinocytes by the application of ultrasound contribute to the ultrasound-enhanced intact skin optical clearing effects.

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