Τετάρτη 18 Νοεμβρίου 2020

Mutations in 3β‐hydroxysteroid‐δ8, δ7‐isomerase paradoxically benefit epidermal permeability barrier homeostasis in mice

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Abstract

Inherited or acquired blockade of distal steps in the cholesterol synthetic pathway results in ichthyosis, due to reduced cholesterol production and/or the accumulation of toxic metabolic precursors, while inhibition of epidermal cholesterol synthesis compromises epidermal permeability barrier homeostasis. We showed here that 3β‐hydroxysteroid‐δ8, δ7‐isomerase‐deficient mice (TD), an analog for CHILD syndrome in humans, exhibited not only lower basal transepidermal water loss rates, but also accelerated permeability barrier recovery despite the lower expression levels of mRNA for epidermal differentiation marker‐related proteins and lipid synthetic enzymes. Moreover, TD mice displayed low skin surface pH, paralleled by increased expression levels of mRNA for sodium/hydrogen exchanger 1 (NHE1), and increased antimicrobial peptide expression, compared to wild type (WT) mice, which may compensate for the decreased differentiation and lipid synthesis. Additionally, in com parison with WT controls, TD mice showed a significant reduction in ear thickness following challenges with either phorbol ester or oxazolone. However, TD mice exhibited growth retardation. Together, these results demonstrate that 3β‐hydroxysteroid‐δ8, δ7‐isomerase deficiency does not compromise epidermal permeability barrier in mice, suggesting that alterations in epidermal function depend on which step of the cholesterol synthetic pathway is interrupted. But whether these findings in mice could be mirrored in humans remains to be determined.

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Topical Application with Conjugated Linoleic Acid Ameliorates 2, 4‐dinitrofluorobenzene‐Induced Atopic Dermatitis‐like Lesions in BALB/c Mice

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Abstract

Atopic dermatitis (AD) is a multifactorial chronic inflammatory skin disease characterized by skin barrier dysfunction, eczematous lesions, pruritus, and abnormal immune responses. In this study, we assessed the therapeutic effect of topical applied conjugated linoleic acid (CLA) on a murine AD model that was developed by repetitive applications of 2, 4‐dinitrofluorobenzene (DNFB). 2% or 5% CLA could markedly ameliorate AD‐like skin lesions, scratching behavior and skin inflammation as evidenced by the reduced inflammatory blood cells, IgE and Th2‐related cytokine levels, and the infiltration of mast cells and inflammatory cells to the dermal tissues. Moreover, topical application with CLA modulated skin barrier repair including maintaining a balanced skin pH and increasing skin hydration, partially mediated by upregulating skin barrier‐related protein, filaggrin (FLG). In addition, topical CLA significantly dose‐dependently inhibited pro‐inflammatory cytokin es including interleukin (IL)‐6, IL‐1β, tumor necrosis factor (TNF)‐α, and pro‐inflammatory enzyme expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase‐2 (COX‐2) in inflamed mice skin. Its anti‐inflammatory effect was associated with the inhibition of DNFB stimulated IκBα and NF‐κB p65 phosphorylation in mouse skin. Taken together, our results suggest that locally applied CLA exerts potentially protective effects against AD lesional skin at least in part, due to regulation of skin barrier function and inflammatory response.

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Laminins and interaction partners in the architecture of the basement membrane at the dermal‐epidermal junction

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Abstract

The basement membrane at the dermal‐epidermal junction keeps the epidermis attached to the dermis. This anatomical barrier is made up of four categories of extracellular matrix proteins: collagen IV, laminin, nidogen and perlecan. These proteins are precisely arranged in a well‐defined architecture through specific interactions between the structural domains of the individual components. Some of the molecular constituents are provided by both fibroblasts and keratinocytes, while others are synthesized exclusively by fibroblasts or keratinocytes. It remains to be determined how the components from the fibroblasts are targeted to the dermo‐epidermal junction and correctly organized and integrated with the proteins from the adjacent keratinocytes to form the basement membrane.

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The Therapeutic Potential of Cannabinoids for Integumentary Wound Management

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Abstract

The increasing legalization of Cannabis for recreational and medicinal purposes in the United States has spurred renewed interest in the therapeutic potential of cannabinoids (CBs) for human disease. The skin has its own endocannabinoid system (eCS) which is a key regulator of various homeostatic processes, including those necessary for normal physiologic wound healing. Data on the use of CBs for wound healing is scarce. Compelling pre‐clinical evidence supporting the therapeutic potential of CBs to improve wound healing by modulating key molecular pathways is herein reviewed. These findings merit further exploration in basic science, translational and clinical studies.

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Superior mediastinal paraganglioma initially suspected of being a mediastinal thyroid goiter

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Publication date: Available online 17 November 2020

Source: Auris Nasus Larynx

Author(s): Ryosuke Takahashi, Hiroaki Kawabe, Nobuaki Koide, Akihisa Tasaki, Kazuchika Ohno, Yosuke Ariizumi, Daisuke Kobayashi, Takahiro Asakage

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Τρίτη 17 Νοεμβρίου 2020

Clival Meningioma Removal through a Suboccipital Retrosigmoid Approach: Operative Video and Technical Nuances

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J Neurol Surg B Skull Base
DOI: 10.1055/s-0040-1705163

Background Clival meningiomas are challenging lesions that need to be managed according to the displacement of the adjacent structures. Lateral skull base approaches are needed to achieve their radical removal; however, they are associated with significant morbidity, especially when the tumor involves the basilar artery, its perforators, brainstem, and lower cranial nerves. Design This is a case of a 79-year-old female patient, diagnosed with a large lower clival meningioma after suffering from headaches. It was offered a conservative treatment but on serial MRI, an increase in the meningioma's size was observed, so it was decided to remove the meningioma using a left suboccipital retrosigmoid approach. Settings On a left three-quarter prone position, with facial nerve, auditory brainstem response, lower cranial nerves, and motor-evoked potentials and somatosensory-evoked potentials neurophysiologic monitoring, a right suboccipital retrosigmoid craniotomy with opening of the foramen magnum was performed, giving enough lateral visualization of the tumor. Broad base tumor pushing backward and aside the vertebral and basilar arteries, cranial nerves (7th–12th), and the brainstem was exposed and removed. Results Near total resection of the meningioma was achieved, leaving a microscopic residual in the entry points of the low cranial nerves without complications. There was no neurological deficit after the surgery. Postoperative MRI revealed no signs of residual tumor. Conclusion: In this case, the regular retrosigmoid approach, extended into the foramen magnum was enough for the removal of this pure clival meningioma.The link to the video can be found at: https://youtu.be/3d6Uj4gjmDU.
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Article in Thieme eJournals:
Table of contents  |  Abstract  |  open access Full text

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IBCC chapter & cast – Ventilator Associated Pneumonia (VAP)

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VAP is a perennial riddle in the intensive care unit.  There are numerous murky diagnostic tests, but no single gold-standard diagnostic test.  Consequently, we are usually left wondering whether or not the patient truly has a VAP.  This makes VAP an unsatisfying diagnosis, as we are continually walking a blurred line between undertreatment and overtreatment. […]

EMCrit Project by Josh Farkas.

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