Fractional Carbon Dioxide Laser is Effective in Amelioration of Pruritus in Primary Cutaneous Amyloidosis: A Clinical and Biochemical Study.

BACKGROUND AND OBJECTIVES: Primary cutaneous amyloidosis (PCA) is a pruritic disease characterized by amyloid deposition in the skin. Interleukin-31 (IL-31) is a pruritus-mediating cytokine. Fractional carbon dioxide (CO2 ) laser has shown efficacy in the treatment of PCA regarding the clinical appearance, histological pattern, and pruritus. The aim of this study is to assess the effect of fractional CO2 laser on pruritus associated with PCA, and analyze whether this effect is related to IL-31 and IL-31 receptor (R) expression. STUDY DESIGN/MATERIALS AND METHODS: The study included 24 patients with PCA and 24 healthy controls. Each patient received four fractional CO2 laser sessions, 4 weeks apart, using the superficial ablative mode. Skin biopsies were taken from patients before and after treatment, as well as controls, for assessment of IL-31 and IL-31R by real-time polymerase chain reaction. RESULTS: Treatment resulted in significant improvement of all clinical parameters, including pruritus (P < 0.001). Patients before treatment had significantly higher IL-31 and IL-31R than controls (P = 0.000 for both). In addition, there was a statistically significant decrease in IL-31 and IL-31R after treatment than their values before treatment (P = 0.000 for both). CONCLUSION: This study confirms the therapeutic efficacy of fractional CO2 laser in treatment of PCA. Reduction of IL-31 and its receptor seems to be one of the involved mechanisms; however, its relation to improvement of pruritus is still not clear. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

Flavonoids of Salvadora persica L. (meswak) and its liposomal formulation as a potential inhibitor of SARS-CoV-2.

Several studies are now underway as a worldwide response for the containment of the COVID-19 outbreak; unfortunately, none of them have resulted in an effective treatment. Salvadora persica L. (Salvadoraceae), commonly known as meswak, is one of the popular plants used by Muslims as an oral hygiene tool. It is documented that the meswak possesses antiviral activity, but no report discusses its use for coronavirus treatment. Herein, a mixture of 11 flavonoids prepared from the aqueous plant extract and its liposomal formulation were shown to inhibit SARS-CoV-2 in an in vitro A549 cell line culture and a RT-PCR test almost as well as the FDA-approved anti-COVID-19 agent, remdesivir. Encapsulation within liposomal formulation led to a highly significant increase in the percentage of inhibition of viral replication from 38.09 ± 0.83 to 85.56 ± 1.12% in a flavonoid mixture and its liposomal preparation, respectively, and this figure approached that obtained for remdesivir (91.20 ± 1.71%). Preliminary tests were also performed, including a total flavonoid assay, a molecular docking study, a 3CL-protease inhibition assay and a cytotoxicity study. It was worthy to find a cheap, readily available, safe natural source for promising anti-SARS-CoV-2 agents, that leak their phytochemicals into the aqueous saliva during regular use as a brushing agent.

Molecular docking reveals the potential of Salvadora persica flavonoids to inhibit COVID-19 virus main protease.

In December 2019, an outbreak of coronavirus disease 2019 (COVID-19) commenced in Wuhan, China and affected around 210 countries and territories in a matter of weeks. It has a phylogenetic similarity to SARS-CoV and it was named coronavirus 2 (SARS-CoV-2) and caused severe acute respiratory syndrome that could lead to death. One of the promising therapeutic strategies for virus infection is the search for enzyme inhibitors among natural compounds using molecular docking in order to obtain products with minimal side effects. COVID-19 virus main protease plays a vital role in mediating viral transcription and replication, introducing it as an attractive antiviral agent target. Metabolic profiling of the aqueous extract of Salvadora persica L. (Salvadoraceae) aerial parts dereplicated eleven known flavonol glycosides using LC-HRESIMS. All the annotated flavonoids exhibited significant binding stability at the N3 binding site to different degrees, except isorhamnetin-3-O-ß-d-glucopyranoside, when compared with the currently used COVID-19 main protease inhibitor, darunavir. Structural similarity between the identified flavonoids enabled the study of the relationship between their structure and interactions with the receptor in the N3 binding site of the COVID-19 main protease. The results indicate that the basic flavonol nucleus possesses activity itself. Moreover, the presence of a rutinose moiety at the 3 position of ring C and absence of an O-methyl group in ring B of the flavonol structure could increase the binding stability. This study provides a scientific basis for the health benefits of the regular use of S. persica as it leaches bioactive flavonoids in the aqueous saliva.

Apocytolysis, a proposed mechanism of blister formation in epidermolysis bullosa simplex.

Epidermolysis bullosa simplex (EBS) is caused by keratin 5 and 14 mutations. In vitro studies revealed that susceptibility to caspase 8-mediated apoptosis is increased in keratin 14 mutated keratinocytes. We aimed to investigate the role of apoptotic/inflammatory pathways in the pathogenesis of EBS by studying the expression of caspase 8 in lesional and non-lesional skin compared to controls. Ten EBS patients proved by electron microscopy and five age and sex matched healthy volunteers were the subjects of this case control study. Caspase 8 expression was studied by immunohistochemistry. Caspase 8 expression in lesional and non-lesional skin was significantly higher than in controls (p < 0.01 and p = 0.013, respectively) with no significant difference between lesional and non-lesional skin. Lesional skin had significantly higher density of dermal infiltrate (p = 0.02). Caspase 8 expression in lesional skin was significantly correlated with the extent of the disease, rate of blistering, and density of dermal infiltrate (r = 0.835; p = 0.003, r = 0.889; p = 0.001 and r = 0.776; p = 0.008 respectively). Caspase 8-mediated apoptosis is an integral component of an orchestra of events conducted by keratin mutation. Apo-cytolysis is proposed to better describe the mechanism of blistering in EBS. The small number of cases is a limitation.

Study of T helper 1 and T helper 2 responses in pemphigus vulgaris patients receiving interferon alpha 2a injections in addition to a standard protocol therapy: a randomized controlled trial.

T helper (Th)1 insufficiency was recently found to be related to the pathogenesis of pemphigus vulgaris (PV). Decreased Th1 response was particularly noticed in the early stages of PV. Therefore, administration of interferon alpha in the early stages of aggressive PV may lead to rapid control of the acute stage of the disease. Our aim was to evaluate the role of interferon alpha in the treatment of PV. 30 patients with acute severe PV (>60 % affection) and 30 age and sex-matched healthy subjects were included in this RCT. Patients were randomly divided into two groups (A and B). Group B patients received interferon retard (one subcutaneous injection/week for 4 weeks) in addition to our protocol for the treatment of PV (systemic pulse corticosteroids/cyclophosphamide in combination with sulphasalazine and pentoxifylline) that was administered to all the included patients. IFN-γ and IL-4 were estimated by ELISA before treatment, after 4 weeks and at the end of the study duration (12 weeks). Clinical assessment was done by PAAS on a biweekly basis. All PV patients showed significantly (P < 0.001) elevated levels of IL-4 and significantly (P < 0.001) depressed mean concentration of IFN-γ as compared with healthy controls. Twelve weeks after therapy both groups showed significant improvement in their mean PAAS being more evident and more rapid in group B. IFN-γ was elevated significantly and IL-4 was dropped significantly in group B patients in comparison to group A (P < 0.001). As a conclusion, interferon therapy in severe PV could achieve a more prompt and better clinical response.