calcipotriene and Edema

Psoriasis involving sensitive skin areas remains difficult to treat because of the side-effects of topical corticosteroids and the irritancy potential of vitamin D3 derivatives. Several clinical trials have demonstrated that calcitriol, the naturally occurring and hormonally active form of vitamin D3, is effective and safe at the dose of 3 microg g(-1) for the treatment of psoriasis affecting the trunk and limbs.. We compared the safety and efficacy of calcitriol 3 microg g(-1) ointment and calcipotriol 50 microg g(-1) ointment in a multicentre, randomized, investigator-blinded, left-right comparison in mild to moderate chronic plaque psoriasis affecting sensitive areas, defined as being the face, hairline, retroauricular and flexural areas. One pair of symmetrical and bilateral target lesions was selected from each area and assessed for perilesional erythema, oedema, and stinging/burning. Global assessment of local tolerability and global improvement were rated by the investigator, and the subjects were asked to evaluate the tolerability and efficacy of each product and to express their global preference.. In the 75 subjects, calcitriol and calcipotriol both led to clearing of at least one target lesion in 21 (28%) of the subjects each. Perilesional erythema (P < 0.001), perilesional oedema (P < 0.02) and stinging/burning (P < 0.001) were all significantly less severe with calcitriol than with calcipotriol. The subjects' evaluation of local tolerability was significantly (P < 0.0001) in favour of calcitriol. Ten treatment-related dermatological events occurred in eight subjects, including one subject who experienced skin discomfort on both sides. All other events occurred only on the calcipotriol-treated side (irritant dermatitis, six subjects; contact dermatitis, one subject). Global assessment of improvement from baseline by the investigators was significantly greater for the calcitriol-treated lesions (P < 0.02). The subjects' global preference was significantly in favour of calcitriol (P < 0.02).. In the present study, calcitriol ointment was found to be better tolerated and would appear to be more effective than calcipotriol ointment in the treatment of psoriasis in sensitive areas.

Topics: Adolescent; Adult; Aged; Axilla; Calcitriol; Dermatologic Agents; Double-Blind Method; Drug Tolerance; Ear, External; Edema; Erythema; Facial Dermatoses; Female; Humans; Male; Middle Aged; Ointments; Patient Satisfaction; Psoriasis; Treatment Outcome

Topics: Administration, Cutaneous; Antineoplastic Combined Chemotherapy Protocols; Calcitriol; Dermatologic Agents; Docetaxel; Edema; Female; Humans; Hyperpigmentation; Intestinal Neoplasms; Lower Extremity; Middle Aged; Ointments; Sclerosis; Skin Pigmentation; Treatment Outcome

In this work, a series of structurally novel benzoxaborole derivatives were designed, synthesized and biologically evaluated as PDE4 inhibitors for battling atopic dermatitis (AD). Among them, the majority exhibited superior PDE4B inhibitory activities to that of the lead compound Crisaborole, an approved PDE4 inhibitor. In particular, 72, the most potent PDE4B inhibitor throughout this series, displayed 136-fold improved enzymatic activity (IC

Topics: Animals; Boron Compounds; Calcitriol; Cyclic Nucleotide Phosphodiesterases, Type 4; Dermatitis, Atopic; Dose-Response Relationship, Drug; Drug Design; Edema; Female; Guinea Pigs; Male; Mice; Mice, Inbred ICR; Molecular Docking Simulation; Molecular Structure; Phosphodiesterase 4 Inhibitors; Rats; Rats, Sprague-Dawley; Structure-Activity Relationship; Tetradecanoylphorbol Acetate

The type 2 cytokines IL-4 and IL-13 promote not only atopic dermatitis (AD) but also the resolution of inflammation. How type 2 cytokines participate in the resolution of AD is poorly known.. Our aim was to determine the mechanisms and cell types governing skin inflammation, barrier dysfunction, and resolution of inflammation in a model of AD.. Mice that exhibit expression of IL-4, IL-13, and MCPT8 or that could be depleted of basophils or eosinophils, be deficient in IL-4 or MHC class II molecules, or have basophils lacking macrophage colony-stimulating factor (M-CSF) were treated with calcipotriol (MC903) as an acute model of AD. Kinetics of the disease; keratinocyte differentiation; and leukocyte accumulation, phenotype, function, and cytokine production were measured by transepidermal water loss, histopathology, molecular biology, or unbiased analysis of spectral flow cytometry.. In this model of AD, basophils were activated systemically and were the initial and main source of IL-4 in the skin. Basophils and IL-4 promoted epidermal hyperplasia and skin barrier dysfunction by acting on keratinocyte differentiation during inflammation. Basophils, IL-4, and basophil-derived M-CSF inhibited the accumulation of proinflammatory cells in the skin while promoting the expansion and function of proresolution M2-like macrophages and the expression of probarrier genes. Basophils kept their proresolution properties during AD resolution.. Basophils can display both beneficial and detrimental type 2 functions simultaneously during atopic inflammation.

Topics: Animals; Basophils; Calcitriol; Cell Differentiation; Cytokines; Dermatitis, Atopic; Diphtheria Toxin; Edema; Eosinophils; Female; Gene Expression; Histocompatibility Antigens Class II; Hyperplasia; Keratinocytes; Male; Mice, Inbred C57BL; Mice, Transgenic; Skin

Topics: Administration, Topical; Adolescent; Anti-Inflammatory Agents; Bandages; Calcitriol; Dermatologic Agents; Drug Therapy, Combination; Edema; Fibrosis; Humans; Kidney Failure, Chronic; Kidney Transplantation; Male; Methotrexate; Methylprednisolone; Peritoneal Dialysis; Skin Diseases; Treatment Outcome; Triamcinolone