Treatment Of Different Skin Diseases Research Articles

AN AUTOMATED SKIN DISEASE DIAGNOSTIC SYSTEM BASED ON DEEP LEARNING MODEL

The use of computer technology has significantly advanced the medical sector, and many computer technologies have been used to develop healthcare, such as the patient management system, monitoring and control systems, and diagnostic systems. Technological advances in healthcare have also helped in saving numerous patients and are constantly improving our quality of life. Technology in the medical sector has also had a major effect on almost all healthcare professional techniques and practices. In order to facilitate rapid diagnosis and treatment of different skin diseases by the use of a deep learning model, this study developed a comprehensive framework to improve the decision-making of dermatologists in Nigeria in terms of the diagnosis of selected skin diseases. The developed system achieved the network accuracy of 98.44 % and the validation accuracy of the test set is 99.44 % as specified by the training results, further testing reveal that the developed system yielded rejection rate of 2.2 % and recognition accuracy of 97.8 %.

The Challenge of Nanovesicles for Selective Topical Delivery for Acne Treatment: Enhancing Absorption Whilst Avoiding Toxicity.

Acne is a common skin disease that affect over 80% of adolescents. It is characterized by inflammation of the hair bulb and the attached sebaceous gland. To date, many strategies have been used to treat acne as a function of the disease severity. However, common treatments for acne seem to show several side effects, from local irritation to more serious collateral effects. The use of topical vesicular carriers able to deliver active compounds is currently considered as an excellent approach in the treatment of different skin diseases. Many results in the literature have proven that drug delivery systems are useful in overcoming the toxicity induced by common drug therapies, while maintaining their therapeutic efficacy. Starting from these assumptions, the authors reviewed drug delivery systems already realized for the topical treatment of acne, with a focus on their limitations and advantages over conventional treatment strategies. Although their exact mechanism of permeation is not often completely clear, deformable vesicles seem to be the best solution for obtaining a specific delivery of drugs into the deeper skin layers, with consequent increased local action and minimized collateral effects.

Cannabidiol induces antioxidant pathways in keratinocytes by targeting BACH1

Cannabidiol (CBD) is a major non-psychotropic phytocannabinoid that attracted a great attention for its therapeutic potential against different pathologies including skin diseases. However, although the efficacy in preclinical models and the clinical benefits of CBD in humans have been extensively demonstrated, the molecular mechanism(s) and targets responsible for these effects are as yet unknown. Herein we characterized at the molecular level the effects of CBD on primary human keratinocytes using a combination of RNA sequencing (RNA-Seq) and sequential window acquisition of all theoretical mass spectrometry (SWATH-MS). Functional analysis revealed that CBD regulated pathways involved in keratinocyte differentiation, skin development and epidermal cell differentiation among other processes. In addition, CBD induced the expression of several NRF2 target genes, with heme oxygenase 1 (HMOX1) being the gene and the protein most upregulated by CBD. CRISPR/Cas9-mediated genome editing, RNA interference and biochemical studies demonstrated that the induction of HMOX1 mediated by CBD, involved nuclear export and proteasomal degradation of the transcriptional repressor BACH1. Notably, we showed that the effect of BACH1 on HMOX1 expression in keratinocytes is independent of NRF2. In vivo studies showed that topical CBD increased the levels of HMOX1 and of the proliferation and wound-repair associated keratins 16 and 17 in the skin of mice. Altogether, our study identifies BACH1 as a molecular target for CBD in keratinocytes and sets the basis for the use of topical CBD for the treatment of different skin diseases including atopic dermatitis and keratin disorders.

Intradermal Delivery of Synthetic mRNA Using Hollow Microneedles for Efficient and Rapid Production of Exogenous Proteins in Skin

In recent years, synthetic mRNA-based applications to produce desired exogenous proteins in cells have been gaining importance. However, systemic delivery of synthetic mRNA can result in unspecific uptake into undesired cells or organs and, thereby, fail to target desired cells. Thus, local and targeted delivery of synthetic mRNA becomes increasingly important to reach the desired cell types and tissues. In this study, intradermal delivery of synthetic mRNA using a hollow microneedle injection-based method was evaluated. Furthermore, an ex vivo porcine skin model was established to analyze synthetic mRNA-mediated protein expression in the skin following intradermal delivery. Using this model, highly efficient delivery of synthetic mRNA was demonstrated, which resulted in detection of high levels of secretable humanized Gaussia luciferase (hGLuc) protein encoded by the microinjected synthetic mRNA. Interestingly, synthetic mRNA injected without transfection reagent was also able to enter the cells and resulted in protein expression. The established ex vivo porcine skin model can be used to evaluate the successful production of desired proteins after intradermal delivery of synthetic mRNAs before starting with in vivo experiments. Furthermore, the use of microneedles enables patient-friendly, painless, and efficient delivery of synthetic mRNAs into the dermis; thus, this method could be applied for local treatment of different skin diseases as well as for vaccination and immunotherapy.

The Safety of Oral Ketoconazole in the Treatment of Skin Diseases (Single Blinded, Therapeutic, Comparative Study)

Background: Ketoconazole was introduced in 1981 as the first in a series of antifungal agents that are characterized by nitrogen-containing ring. Ketoconazole acts against many different kinds of fungi such as candida, dermatophytes and as pergillus. Also oral ketoconazole had proved its effectiveness in the treatment of cutaneous Leishmaniasis. Objective: To evaluate the safety of oral ketoconazole in the treatment of different skin diseases like cutaneous Leishmaniasis (CL), tineacapitis, tineacorporis and tineaversicolor. Patients and Methods: This is a single, blinded, therapeutic, controlled study that was carried out in the Department of Dermatology, Baghdad Teaching Hospital, Baghdad, Iraq, during the time, January 2015 to July 2016. In total, 951 patients with acute cutaneous leishmaniasis, tineacapitis, tineacorporis and tineaversicolor were enrolled in this study. The diagnosis was confirmed by smear and histopathology. Patients were divided into two groups: 51 patients in Group 1; 24 of them were treated with oral ketoconazole tablets 200 mg twice daily for 6 weeks and 27 of them were treated orally with a combination of zinc sulfate 10 mg/kg/day and ketoconazole for 6 weeks. All patients were seen regularly every 2 weeks for 6 weeks of treatment period, then monthly for the next three months as follow up period. Liver enzymes monitoring was done for every patient in this study every two weeks. Elevated liver enzymes were considered as features of hepatotoxicity in the examined patients. While group 2 included 900 patients and was divided into 3 subgroups: A: 600 patients with tineacapitis and tineacorporis, B: 100 patients with tineaversicolor, and C: 200 patients with CL. All patients in group 2 were treated with oral KC tablets 200 mg twice daily for 6 weeks. The dose of oral KC in children is 3.3 - 6.6 mg/Kg/day. All patients in group 2 were not investigated for ketoconazole biochemical side effects but watched for any clinical symptoms and signs of any side effects. Results: After six weeks, 951 patients had completed the treatment. In the first group (51 patients), only two out 27 patients (7.4%) from the combined group showed elevated liver enzymes while the ketoconazole treated group showed no increase in liver enzymes, hence only 3.9% showed elevated liver enzymes that went to normal during follow up. In the second group (900 patients) there were no clinical symptoms and signs in favor of hepatic toxicity or other related organs. Conclusion: Ketoconazole has been used tremendously in treating of different skin diseases including fungal and Leishmania infection but without side effects, accordingly this drug seems safe to be used in treatment of different skin diseases whether adults or children.

OSMOLYTIC AND ADSORPTIVE ACTIVITIES DETERMINATION IN VITRO OF OINTMENT COMPONENTS ON THE BASIS OF CO2 EXTRACT FROM SEEDS OF SCHIZANDRA CHINENSIS

There are data about positive effects from treatment of different skin diseases, sluggishly granulating wounds, and trophic ulcers with drugs based on Schizandra chinensis in literature sources. The purpose of this work is elaboration of soft external drug form – ointment on the basis of CO2 extract of Schizandra chinensis seeds. Biopharmaceutical researches in vitro were carried out to choose optimal ointment composition with osmolytic and absorptive activity. Researches on osmolytic activity determination were conducted by the common method of equilibrium dialysis through semi-permeable membrane; adsorption activity of model ointment compositions was registered on their capability to sorb coloring agent. Thus we have established that all model ointment compositions under consideration have osmolytic (by the efficiency as well as by duration) and adsorptive activity and can be used at different stages of wound process

Excimer UV Radiation in Dermatology

Ultraviolet B (UVB 290-320 nm) radiation has been used in the treatment of different skin diseases. Light sources with narrowband UVB output spectrum have been developed with the aim of increasing the rates of “beneficial to side effect” profile of the treatment. Narrowband UVB phototherapy using fluorescent lamps (TL01, 311∓2nm) has been widely adopted over the past 10 years. Monochromatic Excimer Light (MEL) represents a new source of narrow-band UVB emitting at 308 nm and guarantees a safe and effective approach to different chronic and recurrent skin diseases thanks to its potent and selective immunosuppressant action.

THU0066 Phenotypical and Functional Characteristics of in Vitro Expanded Adipose-Derived Mesenchymal Stem Cells from Patients with Systemic Sclerosis

BackgroundAdult stem cells, expecially those of mesodermal origin (MSCs), have received attention as an ideal source of regenerative capable cells because of their multipotentially and ability to replicate. Regenerative cells...

Application of HPLC-ELSD for the Quantification of 5-Aminolevulinic Acid after Penetration into Human Skin Ex Vivo

5-Aminolevulinic acid (5-ALA) has been used for treatment of different skin diseases (e.g., skin cancer, actinic keratosis (AK), psoriasis, and acne). The quality of the treatment is directly associated to the amount of 5-ALA that penetrates into skin. 5-ALA was extracted from skin samples after performing the experiment with Bronaugh cells for 4 hours. Two methods were developed by applying different column systems and mobile phase compositions: YMC-Pack Hydrosphere C18 column (250 × 4 mm, 5 µm) in series with Hichrom Hypersil H5ODS (150 × 4 mm, 5 µm), mobile phase consisted of 0.1% TFA in water with 2% of ACN (method A); ACE 3AQ column (150 × 4 mm, 3 µm) eluted with 0.05% TFA in water (method B). Exploratory fluorimetric analysis requiring pre-column or post-column derivatization did not warrant the expectations of simple and effective analysis; therefore, ELS detection for 5-ALA was considered. Parallel chromatography was applied for double-validation of the methods in order to correctly evaluate the possibility of ELSD application for 5-ALA detection and the quantification amount in skin extracts. The retention time and adequate lowest limit of quantification (LLOQ) of 5-ALA were determined in both methods: 5.5 min and 20 µg/ml (method A); 6.2 min and 8.4 µg/ml (method B). Both HPLC-ELSD methods proved to be simple, accurate, precise, reliable, and showed reproducible values in the concentration range of 20–200 µg/ml in human skin extracts.

Angelicin induces apoptosis through intrinsic caspase-dependent pathway in human SH-SY5Y neuroblastoma cells

Angelicin is structurally related to psoralens, a well-known chemical class of photosensitizers used for its antiproliferative activity in treatment of different skin diseases. To verify the activity of angelicin, we employed human SH-SY5Y neuroblastoma cells to investigate its cytotoxicity, although its mechanism of action has not yet been fully elucidated. Here, we examined the cellular cytotoxicity of angelicin by cell viability assay, DNA fragmentation by DNA ladder assay, and activation of caspases and Bcl-2 family proteins by western blot analyses. The results of our investigation suggest that angelicin increased cellular cytotoxicity in a dose- and time-dependent manner with IC(50) of 49.56 μM at 48 h of incubation. In addition, angelicin dose-dependently downregulated the expression of anti-apoptotic proteins including Bcl-2, Bcl-xL, and Mcl-1 suggesting the involvement of the intrinsic mitochondria-mediated apoptotic pathway which did not participate in Fas/FasL-induced caspase-8-mediated extrinsic, MAP kinases, and PI3K/AKT/GSK-3β pathway. Furthermore, we clarified the dose-dependent upregulation of caspase-9 and caspase-3 which indicated that angelicin-induced apoptosis is mediated primarily through the intrinsic caspase-mediated pathway. In particular, the caspase-3 inhibitor, DEVD-fmk, induced a reduction in angelicin-induced cytotoxicity which confirmed that the intrinsic caspase-dependent pathway during this apoptosis which did not prevent cytotoxicity using MAP kinases and GSK-3 inhibitor. Taken together, our data shows that angelicin is an effective apoptosis-inducing natural compound of human SH-SY5Y neuroblastoma cells which suggests that this compound may have a role in future therapies for human neuroblastoma cancer.

Increase in γ-globin mRNA content in human erythroid cells treated with angelicin analogs

The aim of the present study was to identify molecular analogs of angelicin (ANG) able to increase erythroid differentiation of K562 cells and expression of gamma-globin genes in human erythroid precursor cells, with low effects on apoptosis. ANG-like molecules are well-known photosensitizers largely used for their antiproliferative activity in the treatment of different skin diseases (i.e., psoriasis, vitiligo, eczema, and mycosis fungoides). To verify the activity of these derivatives, we employed three experimental cell systems: (1) the human leukemic K562 cell line, (2) K562 cell clones stably transfected with a pCCL construct carrying green-EGFP under the gamma-globin gene promoter, and (3) the two-phase liquid culture of human erythroid progenitors isolated from normal donors and beta-thalassemia patients. The results of our study suggest that trimethyl ANG is a powerful inducer of erythroid differentiation, compared with known inducers, such as ANG, cytosine arabinoside, mithramycin, and cisplatin. These data could have practical relevance, because pharmacologically mediated regulation of human gamma-globin gene expression, with the consequent induction of fetal hemoglobin, is considered a potential therapeutic approach in hematological disorders including beta-thalassemia and sickle cell anemia.

220-PREVENTION AND TREATMENT OF POSTSTROKE DEPRESSION WITH MIRTAZAPINE

Recently, a new therapy involving an extracorporal activation of orally administered 8-methoxypsoralen (8-MOP), photosensitizing furocoumarin, is etablished for the treatment of different skin diseases, extracorporeal photopheresis (ECP).The pharmacokinetic profile of 8-MOP has been pursued as part of a clinical study which should assess the efficacy of ECP in patients with progressive systemic sclerosis and cutaneous T-cell lymphoma.The enormous intra-individual variations proofed for plasma as well as buffy coat concentration are unfavourable for oral 8-MOP therapy. Therefore, the introduction of liquid 8-MOP formulation that allows the direct administration of the drug in to the treatment bag of the ECP device is challenging.

Efficacy of Different UV‐emitting Light Sources in the Induction of T‐cell Apoptosis¶

ABSTRACTUltraviolet B(UV‐B) radiation is a modality widely used for the treatment of different skin diseases. One of the major mechanisms of UV‐B immunosuppression in this treatment modality is thought to be an apoptosis‐inducing effect on T cells infiltrating the skin. We examined the T‐cell apoptosis induction capacities of four different UV light sources, with and without UV filters. The xenon chloride (XeCl) laser proved to be the strongest apoptosis inducer. The use of a phtalic acid filter eliminated UV radiation almost completely below 300 nm, which resulted in a severe decrease in the apoptosis‐inducing capacity of different UV‐B sources. Using the results of the measurements with polychromatic UV light sources, the wavelength dependence of UV‐B light for the induction of T‐cell apoptosis was also determined. The regression line of the action spectrum demonstrated a continuous decrease from 290 to 311 nm. The apoptosis‐inducing capacity of the XeCl laser was almost four times higher than the calculated value according to the action spectrum, which might be attributed to the high irradiance of the laser as compared with nonlaser light sources.

Efficacy of different UV-emitting light sources in the induction of T-cell apoptosis.

Ultraviolet B (UV-B) radiation is a modality widely used for the treatment of different skin diseases. One of the major mechanisms of UV-B immunosuppression in this treatment modality is thought to be an apoptosis-inducing effect on T cells infiltrating the skin. We examined the T-cell apoptosis-induction capacities of four different UV light sources, with and without UV filters. The xenon chloride (XeCl) laser proved to be the strongest apoptosis inducer. The use of a phtalic acid filter eliminated UV radiation almost completely below 300 nm, which resulted in a severe decrease in the apoptosis-inducing capacity of different UV-B sources. Using the results of the measurements with polychromatic UV light sources, the wavelength dependence of UV-B light for the induction of T-cell apoptosis was also determined. The regression line of the action spectrum demonstrated a continuous decrease from 290 to 311 nm. The apoptosis-inducing capacity of the XeCl laser was almost four times higher than the calculated value according to the action spectrum, which might be attributed to the high irradiance of the laser as compared with nonlaser light sources.

Drug Monitoring of Orally Administered 8-Methoxypsoralen in Patients Treated with Extracorporeal Photopheresis

Recently extracorporeal photopheresis (ECP), a new therapy involving extracorporeal activation of orally administered 8-methoxypsoralen (8-MOP), has been established for the treatment of different skin diseases. The pharmacokinetic profile of 8-MOP has been pursued in a clinical study which aimed to assess the efficacy of ECP in patients with progressive systemic sclerosis and cutaneous T-cell lymphoma. However, the enormous intraindividual variations in plasma as well as buffy coat concentrations affect the efficacy of oral 8-MOP therapy. Therefore, the introduction of a liquid 8-MOP formulation enabling the direct administration of the drug into the treatment bag of the ECP device is challenging.

Plasma and buffy coat concentration of 8-methoxypsoralen in patients treated with extracorporeal photopheresis

Recently, a new therapy involving an extracorporal activation of orally administered 8-methoxypsoralen (8-MOP), photosensitizing furocoumarin, is established for the treatment of different skin diseases, extracorporeal photopheresis (ECP). The pharmacokinetic profile of 8-MOP has been pursued as part of a clinical study which should assess the efficacy of ECP in patients with progressive systemic sclerosis and cutaneous T-cell lymphoma. The enormous intra-individual variations proofed for plasma as well as buffy coat concentration are unfavourable for oral 8-MOP therapy. Therefore, the introduction of liquid 8-MOP formulation that allows the direct administration of the drug in to the treatment bag of the ECP device is challenging.

Cutaneous phototoxicity reactions.

This paper reviews some potential mechanisms of cutaneous phototoxicity and discusses selected methods of predicting and ranking phototoxic reactions. Phototoxicity is a non-immunological reaction that is induced by the action of light on a photoactive chemical. The phototoxic chemical may be either exogenous or endogenous, and if exogenous may include topical or systemic agents. Examples of phototoxic agents include psoralens (e.g. 5-methoxypsoralen, 8-methoxypsoralen, as well as the isopsoralens). Psoralens are used therapeutically for the treatment of different skin diseases and psoralen-like chemicals may be present in perfumes and cosmetics. Phototoxic reactions can be evaluated visually in animals. The hairless mouse has also proved useful with skin thickening as a marker of dermal oedema and the induction of polyamine biosynthetic enzymes, as well as other biochemical changes being indicative of cutaneous phototoxicity. In vitro tests of phototoxicity include the Candida albicans assay as well as bacterial mutagenicity. For example, in the latter category different psoralens vary in their ability to induce mutagenicity in Salmonella typhimurium strains, an assay which can provide rapid screening of potential phototoxicity of chemicals. For human testing, phototoxic chemicals can be delivered topically or orally, and in conjunction with appropriate ultraviolet radiation will produce phototoxic reactions which can be evaluated for intensity of response.