RoeKo: Phase-contrast imaging looks set for clinical use

After years in development, phase-contrast imaging is ready for clinical use,...

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from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2rNzAHE
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Deficiency of filaggrin regulates endogenous cysteine protease activity, leading to impaired skin barrier function

Summary

Background

Atopic dermatitis (AD) is a common inflammatory skin disorder, characterized by skin barrier defects and enhanced allergen priming. Null mutations in the filaggrin gene (FLG) are strongly associated with moderate to severe AD, but the pathways linking barrier dysfunction and cutaneous inflammation are still largely unknown.

Aim

To assess alteration of endogenous cysteine protease activity in FLG-deficient keratinocytes, and to determine whether the alteration in cysteine protease activity affects epidermal barrier function and associated gene and protein expression.

Methods

We established a stable FLG knockdown cell line, and reconstructed epidermal equivalents in vitro. Barrier function of the reconstructed epidermis, the barrier-associated genes and proteins, and the activity of endogenous cysteine proteases were tested. Inhibitors of cysteine proteases were used to further evaluate the role of endogenous cysteine proteases in epidermal barrier function.

Results

FLG knockdown induced impaired epidermal barrier function. Microarray, western blotting and fluorescence staining showed reduced expression of K10, ZO-1, E-cadherin, claudin-1 and occludin in FLG knockdown keratinocytes. Compared with cysteine protease activity in control cells, protease activity was dramatically enhanced in FLG knockdown keratinocytes. Furthermore, administration of cysteine protease inhibitors significantly recovered expression of K10 and tight junction proteins, and the barrier defect induced by FLG deficiency.

Conclusions

This is the first observation of elevated endogenous cysteine protease activity in FLG-deficient keratinocytes, which may play an important role in impaired barrier function in AD skin. Modulation of cysteine protease activity might be a novel therapeutic approach for AD treatment.

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Skin involvement as the first symptom of rapidly progressive ALK-positive systemic anaplastic large cell lymphoma

Summary

Systemic anaplastic large cell lymphomas (sALCLs) comprise a heterogeneous group of relatively rare T-cell non-Hodgkin lymphomas that are characterized by CD30 expression. Anaplastic lymphoma kinase (ALK)-positive ALCL is a type of sALCL that commonly involves lymph nodes and extranodal sites. Skin involvement usually presents as tumours, nodules and ulcers. We describe an unusual case of ALK-positive ALCL in an 11-year-old Chinese boy, who initially presented with skin eruption with rapid progression and poor prognosis. This case emphasizes the value of clinical factors to predict the prognosis of ALK-positive sALCL, and we recommend close collaboration between dermatologists, pathologists and haematologists/oncologists to assure the correct diagnosis and treatment.

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A recent-onset ulcerated nodular plaque on the scalp

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Preclinical pilot study monitoring topical drug penetration and dermal bioavailability of a peptidase inhibitor from different galenic formulations into pig dermis, using cutaneous microdialysis

Summary

Background

Cutaneous microdialysis (CM) is an ex vivo technique that allows study of tissue chemistry, including bioavailability of actual tissue concentration of unbound drug in the interstitial fluid of the body.

Aim

To test the penetration and dermal bioavailability of galenic formulations of the small-molecule IP10.C8, a dual-protease inhibitor of the dipeptidyl peptidase and aminopeptidase families.

Methods

Using CM, we tested the penetration and dermal bioavailability of IP10.C8 into the dermis and subcutis of pigs, and determined the tissue concentration of IP10.C8 enzymatically, using an enzyme activity assay (substrate Gly-Pro-pNA) and high performance liquid chromatography.

Results

Dermal bioavailability was enhanced by using microemulsion or the addition of the penetration enhancer oleic acid to a hydroxyethylcellulose (HEC) gel formulation. Dermal bioavailability was also enhanced when galenic formulations were prepared with higher pH (7.5 vs. 6.5) or higher drug concentration (5% vs. 1%) in HEC gel.

Conclusion

It seems possible, using CM for topical skin penetration testing in anaesthetized domestic pigs, to test the bioavailability of newly designed drugs. However, the experimental time is limited due to the anaesthesia, and is dependent on drug recovery. Validation of this technique for routine use is challenging, and more experiments are needed to validate this preclinical set-up.

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Topical capsaicin 8% for the treatment of neuropathic itch conditions

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Integration of reflectance confocal microscopy into clinical practice for the management of lentigo maligna

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