Synthesis of a New Type of Trans-Decalin Vitamin D Analogue through a Dyotropic Ring Expansion

A new vitamin D analogue with a trans-fused decalin as the CD-ring system and containing a sulphur atom in the side chain has been synthesized in our research group. The obtention of this analogue is based on a recently discovered transformation of hydrindane cores into decalins through a dyotropic ring expansion in very mild conditions.

Calcipotriene 0.005%/Betamethasone Dipropionate 0.064% Foam as a Treatment for Nail Psoriasis

Combination topical corticosteroids and vitamin D analog treatments for nail psoriasis are widely used in cream and ointment vehicles, but patients may prefer a foam vehicle due to ease of application and favorable cosmetic appearance. Calcipotriene 0.005%/betamethasone dipropionate 0.064% (Cal/BD) aerosol foam is an FDA approved therapy for plaque psoriasis, but may also be an effective treatment for nail psoriasis in a novel aerosol foam. We present a case series of 3 patients with mild to moderate nail psoriasis who responded positively to treatment with Cal/BD aerosol foam applied 1-2 times daily to affected nails for at least 6 weeks. Reduction of nail plate surface abnormalities and a decrease in inflammation of the nail folds were assessed with clinical evaluation and dermoscopy, and documented with serial photography. While further research on the efficacy and safety of Cal/BD aerosol foam as a treatment for nail psoriasis is needed, this report suggests its potential as a combination topical vitamin D analogue and high potency steroid in a foam vehicle.

Comparative Evaluation of Efficacy Between Topical Calcipotriol Used Along With Topical Clobetasol And Topical Clobetasol Monotherapy In Treatment Of Alopecia Areata: A Randomised Clinical Trial

Introduction: Alopecia Areata (AA) is a hair disorder characterised by non-scarring, patchy loss of hair from scalp and other parts of the body. For the treatment of AA, topical steroid is one of the first line therapeutic options. Topical vitamin D analogue Calcipotriol has immunomodulatory action. Vitamin D receptors (VDR) are present in the hair follicles,therefore for treatment of AA topical vitamin D analogue Calcipotriol can be considered. Aim: To comparatively evaluate the role in terms of efficacy of topical vitamin D analogue Calcipotriol when used along with topical Clobetasol in comparison to topical Clobetasol used alone for AA treatment. Materials and Methods: In this randomised, open label, clinical study, sixty patients (age 20-32 years) diagnosed with AA were randomly assigned into two groups, thirty patients in each from Sept 2019 to Feb 2020. Topical Clobetasol (0.05%) was applied on the affected area twice a day for 24 weeks by Group A patients. While both topical Clobetasol (0.05%) and topical Calcipotriol (0.005%) was applied on the affected area twice daily for 24 weeks by Group B patients. Parametery like Age, Serum Hydroxy Vitamin D (25(OH)D) and SALT Score were mesured at baseline. At regular intervals of time (i.e baseline, 6,12,24 weeks), SALT (Severity Of Alopecia Tool) score was evaluated. Mean values of the data were evaluated using student's t-test and chi-square test based on whether the data was quantitative or qualitative in nature respectively. p<0.05 was considered statistically significant. Results: With respect to age and gender distribution both the groups were comparable (p>0.05). For patients of group A and group B the mean values of SALT score at baseline were 10.45±5.25 and 9.85±4.95, respectively (p=0.65). In patients of Group A and Group B towards the end of 24 weeks the mean values of SALT score decreased to 5.98±4.32 (p=0.0007) and 3.66±3.53 (p=0.0001), with a greater decrease in SALT score seen in Group B (p=0.05) i.e., the group in which patients were treated with topical calcipotriol 0.005% along with topical Clobetasol 0.05%. Conclusion: Topical calcipotriol 0.005% lotion used along with topical Clobetasol 0.05% lotion had higher efficacy than topical Clobetasol 0.05% lotion used alone, in the treatment of AA.

Cytosolic sequestration of the vitamin D receptor as a therapeutic option for vitamin D-induced hypercalcemia

The bioactive vitamin D3, 1α,25(OH)2D3, plays a central role in calcium homeostasis by controlling the activity of the vitamin D receptor (VDR) in various tissues. Hypercalcemia secondary to high circulating levels of vitamin D3 leads to hypercalciuria, nephrocalcinosis and renal dysfunctions. Current therapeutic strategies aim at limiting calcium intake, absorption and resorption, or 1α,25(OH)2D3 synthesis, but are poorly efficient. In this study, we identify WBP4 as a new VDR interactant, and demonstrate that it controls VDR subcellular localization. Moreover, we show that the vitamin D analogue ZK168281 enhances the interaction between VDR and WBP4 in the cytosol, and normalizes the expression of VDR target genes and serum calcium levels in 1α,25(OH)2D3-intoxicated mice. As ZK168281 also blunts 1α,25(OH)2D3-induced VDR signaling in fibroblasts of a patient with impaired vitamin D degradation, this VDR antagonist represents a promising therapeutic option for 1α,25(OH)2D3-induced hypercalcemia.

Selocalcitol: Scope of inhalational formulation for prevention and cure of COVID-19 illness

Vitamin D has generated interest in the context of COVID-19 pandemic. Some authorities believe that it is beneficial; others think that without proven deficiency it should not be administered. The results of clinical trial are still awaited. Therefore nothing regarding the matter is conclusively known. In this context we believe that selocalcitol, a Vitamin D analogue if administered via inhalational route, has the potential to prevent SARS-CoV2 infection. The basis of this idea is presented here.

Effect of Vitamin D Analogue on Rosuvastatin-Induced Myopathy in Wistar Rats

Objectives. Statin-induced myopathy is one of the major causes of poor adherence and discontinuation of this medication. There are contrary results regarding association of vitamin D insufficiency with statin-induced myopathy. This study was done to determine the effect of the vitamin D3 analogue alfacalcidol on Rosuvastatin-induced myopathy in rats. Methodology. Animals were divided into six groups with 6 rats in each group. Groups I and II acted as controls, Group III and Group IV were administered Rosuvastatin 120 mg/kg/day and 160 mg/kg/day, Groups V and VI were administered alfacalcidol 0.1 μg/kg/day in addition to Rosuvastatin 120 mg/kg/day and 160 mg/kg/day, respectively. All drugs were administered orally for 15 days. Plasma creatine kinase (CK) levels were estimated on day 10 and day 15. Animals were sacrificed and muscles were sent for histopathological examination. Results. On day 10, Groups V and VI showed a statistically significant increase in plasma CK levels as compared to the control (p<0.001) and were significantly lower (p<0.001) as compared to Groups III and IV, respectively. However, on day 15, plasma CK levels in Groups V and VI were comparable to those of control groups with a nonsignificant difference (p>0.05). On comparing the histology, Groups V and VI showed a significant difference as compared to statin-only groups (Groups III and IV) as there were signs of regeneration, less splitting, and fragmentation of muscle fibres. Conclusion. The present study shows that the vitamin D analogue alfacalcidol prevents statin-induced myopathy. The serum CK levels are comparable to the control group on day 15 of vitamin D administration.