Assessment of serum concentrations of matrix metalloproteinase 1, matrix metalloproteinase 2 and tissue inhibitors of metalloproteinases 1 in atopic dermatitis in correlation with disease severity and epidermal barrier parameters.

INTRODUCTION: Matrix metalloproteinases (MMPs) are a group of proteolytic enzymes, conditioning the integrity of skin cells, however, their role in the inflammatory process of atopic dermatitis (AD) and the direct effect on the epidermal barrier parameters remain unexplained. AIM: To assess MMP-1, MMP-2, tissue inhibitors of metalloproteinases (TIMP)-1 concentrations in blood serum in the context of transepidermal water loss (TEWL) and stratum corneum hydration in AD. Moreover, serum levels of MMPs and TIMP-1 were analysed in relation to the Eczema Area and Severity Index (EASI). MATERIAL AND METHODS: Forty-three AD patients and 22 control group subjects have been investigated. Serum concentrations of MMP-1, MMP-2, and TIMP-1 have been evaluated with ELISA. TEWL and stratum corneum hydration have been assessed with a TM300 Tewameter and a CM825 Corneometer. Skin lesions in patients with AD have been evaluated with the Eczema Area and Severity Index. RESULTS: MMP-1 and MMP-2 serum concentrations were significantly higher in the AD group. The results of TIMP-1 serum concentration were similar for both groups. The correlation between the serum concentration and the EASI was demonstrated only for MMP-2 for patients with severe and moderate AD. Patients with AD and TIMP-1 serum concentration greater than MMP-1 presented lower TEWL and higher epidermal hydration. CONCLUSIONS: The results of this study warrant further investigation. The predominance of TIMP-1 over MMP-1 in blood serum can potentially limit TEWL and maintain the proper water content of the epidermis. Future work is necessary to establish how reliable the role of MMP-2 concentration is as an indicator of the severity of AD.

Evaluation of the effect of the interleukin-25 serum concentration on the intensity of the symptoms of atopic dermatitis and epidermal barrier.

INTRODUCTION: Interleukin 25 (IL-25) is a cytokine with proinflammatory and anti-inflammatory effects, and its biological function of reciprocal epidermal hyperplasia and of inhibiting the filaggrin synthesis points to an essential role connecting the inflammatory process with damage to the epidermal barrier in the course of atopic dermatitis (AD). AIM: To assess the IL-25 in serum concentration in AD patients and to analyse its possible correlation with the disease intensity and selected epidermal barrier parameters such as transepidermal water loss (TEWL). MATERIAL AND METHODS: The study involved 43 patients with AD and 22 healthy volunteers. The IL-25 concentration was measured using the ELISA method. The intensity of disease symptoms was investigated using W-AZS and EASI indicators. The epidermal barrier was evaluated using a Tewameter TM300 and Corneometer CM825. RESULTS: The concentration of IL-25 in serum was higher in the study group than in the control group. IL-25 serum concentration correlates with W-AZS/EASI in patients with a severe and moderate course of AD. The concentration of IL-25 affects the TEWL within the affected, evaluated skin surface. CONCLUSIONS: An elevated IL-25 concentration in serum is characteristic for patients with moderate and severe AD intensity. The IL-25 concentration in serum correlates with TEWL and with the moisture level in the affected area. However, further studies are necessary to determine the role played by IL-25 in the course of the disease and how it affects the functional parameters of the epidermal barrier.

Increased number of endothelial progenitor cells in the blood of patients with psoriasis vulgaris.

Introduction: Psoriasis vulgaris (PsV) is a common dermatosis characterized by excessive activation of neovascularization. Latest research has shown that endothelial progenitor cells (EPCs) are a crucial factor involved in the repair of endothelial injury and formation of new blood vessels, in a process termed postnatal vasculogenesis. However, the exact mechanism of creating psoriatic skin patches and the involvement of EPCs in this process remains unknown. Aim: To evaluate the number of EPCs in the blood of patients with PsV, characterized by the expression of specific cell surface markers, including CD45-, CD31+, CD34+ and CD133+. Material and methods: A total of 49 patients suffering from PsV and 40 healthy volunteers were enrolled in the study. The number of EPCs in each of the volunteers' whole blood samples was measured with a FACSCalibur flow cytometer using monoclonal antibodies directed against antigens specific for EPCs. Results: The number of EPCs was significantly higher in patients with psoriasis compared with the controls (p = 0.0007) and inversely correlated with disease severity assessed by PASI score (R = -0.2935, p = 0.0407). Statistical analysis did not show significant relations between the count of EPCs and age, body mass index, gender, disease duration, blood pressure, extent of itching, severity and frequency of pruritus, presence of bruises, vitamin D supplementation and smoking habit. Conclusions: The results of our studies indicate that patients with psoriasis showed an increased mobilization of EPCs compared with healthy individuals which correlated negatively with disease severity.

Expression of CD1a, CD207, CD11b, CD11c, CD103, and HLA-DR receptors on the surface of dendritic cells in the skin of patients with atopic dermatitis.

INTRODUCTION: Atopic dermatitis (AD) is a chronic skin disorder of unknown etiopathogenesis. Its development is based on the influence of environmental factors, genetic and immunologic disorders. Undoubtedly, an important role is played by changes in quantitative and qualitative information on dendritic cells. AIM: Assessment of CD1a, CD207, CD11b, CD11c, CD103, and HLA-DR receptors on the surface of dendritic cells in the skin of patients with atopic dermatitis. MATERIAL AND METHODS: The study group consisted of 45 patients with clinically diagnosed AD from whom biopsies were taken from the lesions. The control group was the material of 20 healthy people. To carry out the study the method of indirect immunofluorescence double staining reaction was used. RESULTS: Studied receptors gave positive reactions in both groups. The number of cells in healthy individuals was significantly lower than in patients. They also differed in appearance and location of the skin. CONCLUSIONS: The CD1a/CD207 and CD1a/CD11c, CD1a/HLA-DR cell density was higher in AD patients compared to controls. There were differences in the location and appearance of the cells of AD patients compared to controls. All cells in the epidermis identified with antibodies CD1a, CD11c and CD207 were dendritic cells.

Overall clinical and trichoscopic analysis performed in patients who underwent pressurized intraperitoneal aerosol chemotherapy (PIPAC) treatment for peritoneal carcinomatosis - initial trial preliminary report.

INTRODUCTION: Cutaneous adverse events are among the remaining problematic issues of current oncology. The term peritoneal carcinomatosis (PC) refers to the advanced cancer stage. The innovative treatment of PC includes the use of pressurized intraperitoneal aerosol chemotherapy (PIPAC). AIM: To present a preliminary report from an initial trial aimed at an overall clinical and trichoscopic analysis performed in patients who underwent PIPAC treatment due to PC. MATERIAL AND METHODS: For all steps of this study we obtained the consent of the local bioethics commission #KB 196/2018. Three different hair assessment methods were used in our study: 1) general clinical and patient self-feeling assessment; 2) hair pull test; 3) and trichoscopic analysis. RESULTS: No hair or scalp disorders were noted in the observation period. In the self-feeling test assessment the vast majority recognized their hair as being of comparable quality or even better in quality compared to previous forms of chemotherapy they had undergone. In all patients we observed a reduction of hair loss in the pull test in the hospitalization period. In trichoscopic analysis we found all determinants and signs of hair disorders in the assessed group. CONCLUSIONS: The PIPAC is safe and is not a burdensome or aggressive form of therapy, especially according to the very important factors influencing the potential quality of hair and hair loss. The authors, however, realize that to obtain comprehensive results and evaluate this novel and promising method we need to perform more research without any limitations like those in our study.

Investigation of oxidative stress in patients with alopecia areata by measuring the levels of malondialdehyde and ceruloplasmin in the blood.

INTRODUCTION: Alopecia areata (AA) is a chronic, inflammatory and autoimmune disease, presenting with non-scarring hair loss. Although the precise etiopathogenesis of AA remains unknown, oxidative stress is thought to play a role. AIM: To investigate the role of oxidative stress in AA by measuring the levels of plasma and erythrocyte malondialdehyde (MDA) and the ceruloplasmin (CER) in serum. MATERIAL AND METHODS: The study included 24 AA patients and a control group consisting of 24 age- and sex-matched healthy volunteers. The levels of MDA and CER were measured and compared between groups. RESULTS: Plasma MDA levels were significantly higher (p < 0.05) in patients with AA compared with controls. No significant difference was observed in MDA erythrocyte levels (p = 0.990) between the study group and the control group. Ceruloplasmin level was higher in the AA group, but this increase was not statistically significant (p = 0.156). CONCLUSIONS: Patients with AA displayed significant plasma MDA levels, which could lead to damage in erythrocytes exposed to high concentrations of free radicals. These results demonstrate the presence of an imbalance in the oxidant-antioxidant system and support the concept of a possible role of oxidative stress in AA etiopathogenesis.

Abnormal plasma lipids profile in women with post-adolescent acne.

INTRODUCTION: Acne vulgaris is a multifactorial chronic inflammatory disease that is increasingly recognized in adult women. AIM: To investigate a relationship between plasma lipids profile and acne in women and a correlation between selected clinical features of acne (severity, age of onset, location of lesions and the presence of comedones) and lipids profile. MATERIAL AND METHODS: Sixty-four adult women with post-adolescent acne and 20 healthy controls were included in the study. Plasma total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) levels were determined in all the subjects. RESULTS: Adult women with acne had statistically significantly increased levels of TC, TG and LDL-C compared to healthy controls (p < 0.05). The level of HDL-C did not differ between the two groups. There was no relationship between higher levels of TC, TG and LDL-C and a clinical picture of acne. CONCLUSIONS: Acne in adult women is likely to be associated with increased levels of TC, TG and LDL-C. This abnormality seems to be important in the pathogenesis of adult acne and could be a result of high fatty acid diet. Performing a lipid profile examination in women with acne should be taken into account when screening patients and followed by appropriate dietary recommendations.

Nanoparticle as a novel tool in hyperthermic intraperitoneal and pressurized intraperitoneal aerosol chemotheprapy to treat patients with peritoneal carcinomatosis.

The treatment of peritoneal surface malignances has changed considerably over the last thirty years. Unfortunately, the palliative is the only current treatment for peritoneal carcinomatosis (PC). Two primary intraperitoneal chemotherapeutic methods are used. The first is combination of cytoreductive surgery (CRS) and Hyperthermic IntraPEritoneal Chemotherapy (HIPEC), which has become the gold standard for many cases of PC. The second is Pressurized IntraPeritoneal Aerosol Chemotheprapy (PIPAC), which is promising direction to minimally invasive as safedrug delivery. These methods were improved through multicenter studies and clinical trials that yield important insights and solutions. Major method development has been made through nanomedicine, specifically nanoparticles. Here, we are presenting the latest advances of nanoparticles and their application to precision diagnostics and improved treatment strategies for PC. These advances will likely develop both HIPEC and PIPAC methods that used for in vitro and in vivo studies. Several benefits of using nanoparticles will be discussed including: 1) Nanoparticles as drug delivery systems; 2) Nanoparticles and Near Infrred (NIR) Irradiation; 3) use of nanoparticles in perioperative diagnostic and individualized treatment planning; 4) use of nanoparticles as anticancer dressing's, hydrogels and as active beeds for optimal reccurence prevention; and 5) finally the curent in vitro and in vivo studies and clinical trials of nanoparticles. The current review highlighted use of nanoparticles as novel tools in improving drug delivery to be effective for treatment patients with peritoneal carcinomatosis.

Changes of Langerhans cells during skin ageing.

INTRODUCTION: During the process of skin ageing, changes occur in all skin layers and all cells, including the Langerhans cells. AIM: To assess whether any quantitative difference in the number of CD1a+ LC cells/mm2 and HLA-DR+ LC cells/mm2 as well as in their morphological features can be observed during the course of different types of skin ageing. MATERIAL AND METHODS: The study was conducted in a group of 60 women, which was divided into three independent groups: group I with symptoms of menopausal skin ageing, group II with symptoms of photoageing, group III with symptoms of chronological ageing. Skin biopsy samples were taken from the pre-auricular region from all of the participants. The number of CD1a+ LC cells/mm2 and HLA-DR+ LC cells/mm2 as well as their morphological features were evaluated. RESULTS: The frequency of CD1a+ LC and HLA-DR+ LC in all the studied groups was diverse. In groups I and III, the LC with large cell bodies and long, multi-branched processes were the majority. In group II, the LC had small cell bodies and their processes were mainly short and unbranched. CONCLUSIONS: The obtained results indicate the presence of quantitative and morphological changes of the CD1a+ LC and HLA-DR+ LC during the course of different types of skin ageing.

Air pollution, UV irradiation and skin carcinogenesis: what we know, where we stand and what is likely to happen in the future?

The link between air pollution, UV irradiation and skin carcinogenesis has been demonstrated within a large number of epidemiological studies. Many have shown the detrimental effect that UV irradiation can have on human health as well as the long-term damage which can result from air pollution, the European ESCAPE project being a notable example. In total, at present around 2800 different chemical substances are systematically released into the air. This paper looks at the hazardous impact of air pollution and UV and discusses: 1) what we know; 2) where we stand; and 3) what is likely to happen in the future. Thereafter, we will argue that there is still insufficient evidence of how great direct air pollution and UV irradiation are as factors in the development of skin carcinogenesis. However, future prospects of progress are bright due to a number of encouraging diagnostic and preventive projects in progress at the moment.

The use of stem cells in aesthetic dermatology and plastic surgery procedures. A compact review of experimental and clinical applications.

The aim of this paper was to collect currently available data related to the use of stem cells in aesthetic dermatology and plastic surgery based on a systemic review of experimental and clinical applications. We found that the use of stem cells is very promising but the current state of art is still not effective. This situation is connected with not fully known mechanisms of cell interactions, possible risks and side effects. We think that there is a big need to create and conduct different studies which could resolve problems of stem cells use for implementation into aesthetic dermatology and plastic surgery.

The possible role of diet in the pathogenesis of adult female acne.

Acne in adults is a chronic, increasingly common disease, especially among women. It differs in pathogenesis and clinical presentation from adolescent acne. Acne in adults is associated with Western diet, defined as high consumption of milk, high glycemic load and high calorie intake. Metabolic signals of this diet result in a significant increase in insulin/insulin growth factor 1 serum level and consequently in the molecular interplay of mammalian target of rapamycin complex 1 kinase (mTORC1)/forkhead box protein 1 (FoxO1) mediated nutrient signaling, leading to increased proliferation of keratinocytes, increased lipogenesis and sebum production and finally to aggravation of acne.

Use of Adipose-Derived Stem Cells to Support Topical Skin Adhesive for Wound Closure: A Preliminary Report from Animal In Vivo Study.

The aim of this study was to determine the local and systemic effects of adipose-derived stem cells (ADSCs) as a component of topical skin adhesive in an animal artificial wound closure model. In presented study the cosmetic effects, histological analysis, mechanical properties, and cell migration have been assessed to evaluate the usefulness of ADSCs as supporting factor for octyl blend cyanoacrylate adhesive. The total of 40 rats were used and divided into six groups. In the Study Group, ADSCs were administered by multipoint injection of the six surrounding intrawound areas with additional freely leaving procedure of the cells between the skin flaps just before applying adhesive to close the wound. Five control groups without using ADSCs, utilizing different types of standard wound closure, were created in order to check efficiency of experimental stem cell therapy. In our study, we proved that ADSCs could be used effectively also as a supportive tool in topical skin adhesive for wound closure. However we did not achieve any spectacular differences related to such aspects as better mechanical properties or special biological breakthroughs in wound healing properties. The use of stem cells, especially ADSCs for wound closure can provide an inspiring development in plastic and dermatologic surgery.

Is mTOR Inhibitor Good Enough for Treatment All Tumors in TSC Patients?

Tuberous sclerosis complex (TSC) is an autosomal dominant and multi-system genetic disorder in humans. TSC affects around 25,000 to 40,000 individuals in the United States and about 1 to 2 million individuals worldwide, with an estimated prevalence of one in 6,000 newborns. TSC occurs in all races and ethnic groups, and in both genders. TSC is caused by defects or mutations in two genes, TSC1 and TSC2. Loss of TSC1/TSC2 leads to dysregulation of mTOR, resulting in aberrant cell differentiation and development, and abnormal enlargement of cells. TSC is characterized by the development of benign and/or malignant tumors in several organs including renal/liver angiomyolipomas, facial angiofibroma, lymphangiomyomatosis, cardiac rhabdomyomas, retinal astrocytic, renal cell carcinoma, and brain subependymal giant cell astrocytomas (SEGA). In addition, TSC disease causes disabling neurologic disorders, including epilepsy, mental retardation and autism. Particularly problematic are the development of renal angiomyolipomas, which tend to be larger, bilateral, multifocal and present at a younger age compared with sporadic forms. In addition, SEGA block the flow of fluid within the brain, causing a buildup of fluid and pressure that leads to blurred vision and seizures. In the current review, we describe the pathology of TSC disease in key organs and summarize the use of mTOR inhibitors to treat tumors in TSC patients.

Anti-proliferative and cytotoxic activity of rosuvastatin against melanoma cells.

INTRODUCTION: Statins are considered potential candidate agents for melanoma chemoprevention. Statin-induced mevalonate pathway inhibition leads to reduction of cholesterol synthesis and also to decreased cellular levels of non-steroidal isoprenoids, geranylgeranyl pyrophosphate and farnesyl pyrophosphate. This results in the impairment of protein prenylation which affects carcinogenesis. AIM: To analyze anti-proliferative and cytotoxic activity of rosuvastatin against melanoma cells. MATERIAL AND METHODS: Melanoma cell lines (A375 and WM1552C) and normal fibroblasts (BJ) were used as the primary research material. Cells were treated with rosuvastatin at concentrations ranging from 0.01 µM to 10 µM. Cell viability was analyzed with the use of an MTT assay. Expression of proliferation marker Ki67 was assessed on the basis of immunofluorescence staining. RESULTS: Rosuvastatin reduced A375 and BJ cell viability in a time- and dose-dependent manner. After 72 h incubation, the IC50, half maximal inhibitory concentration, was 2.3 µM for melanoma cells and 7.4 µM for normal fibroblasts. In turn, rosuvastatin exhibited relatively lower activity against WM1552C cells. A significant reduction of Ki67 expression was also noted for BJ fibroblasts after prolonged incubation with the tested drug. CONCLUSIONS: The results indicate that the anti-melanoma properties of rosuvastatin are highly dependent on the tumor cell line assessed. However, the concentrations required to decrease melanoma cell viability in vitro exceed the plasma concentrations reached in patients treated with rosuvastatin at well-tolerated doses. What is more disturbing, reduction of proliferation and viability observed in BJ fibroblasts indicated that rosuvastatin at high doses may be toxic for normal cells.

Keratinization Disorders and Genetic Aspects in Palmar and Plantar Keratodermas.

Palmoplantar keratoderma (PPK) is a heterogeneous group of hereditary and acquired disorders characterized by abnormal thickening of the palms and soles. There are three clinical patterns: diffuse, focal, and punctuate. Palmoplantar keratodermas can be divided into the following functional subgroups: disturbed gene functions in structural proteins (keratins), cornified envelope (loricrin, transglutaminase), cohesion (plakophilin, desmoplakin, desmoglein 1), cell-to-cell communication (connexins) and transmembrane signal transduction (cathepsin C). Unna-Thost disease is the most common variety of hereditary PPK. Mutations in keratin 1 have been reported in Unna-Thost disease. We report 12 cases in which Unna-Thost disease was diagnosed. Genealogical study demonstrated that the genodermatosis was a familial disease inherited as an autosomal dominant disorder. Dermatological examination revealed yellowish hyperkeratosis on the palms and soles. Oral mucosa, teeth, and nails remained unchanged. Histopathological examination of the biopsy sample taken from the soles of the patients showed orthokeratotic keratosis, hypergranulosis, and acanthosis without epidermolysis.

The prevalence of mutations in the gene encoding filaggrin in the population of Polish patients with atopic dermatitis.

INTRODUCTION: The genetic background of atopic dermatitis (AD) is complex, involves many genes and their participation varies in varied populations, and depends on the intensity and course of a disease. Changes in the nucleotide sequence of the FLG gene and a reduced number or a deficit of the functional product of processed profilaggrin can be one of risk factors for atopic dermatitis. AIM: To determine the prevalence of R501X and 2282del4 mutations of the FLG gene in patients with AD. MATERIAL AND METHODS: The studied group included 60 patients with clinically diagnosed AD, and the control group included 61 healthy volunteers. The study protocol included collection of biological material for tests, DNA isolation and evaluation of its quality and quantity, and PCR amplification of the isolated genetic material. RESULTS: In the studied group, both changes in the nucleotide sequence of the FLG gene were detected and in the control group no tested mutations were detected. In 18 (30%) patients with AD, 22 mutations (4 heterozygous and 1 homozygous ones of R501X and 10 heterozygous and 7 homozygous ones of 2282del4) were detected. CONCLUSIONS: A high rate of mutations of the FLG gene in patients with clinically diagnosed AD and pathologically dry skin was observed in the studied population. The 2282del4 mutation occurred more often than R501X.