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Study and Evaluation of Topically Applied Ceramides onto Disrupted Skin Barrier
Svobodová, Marie ; Kováčik, Andrej (advisor) ; Vraníková, Barbora (referee)
Department of Pharmaceutical Technology Author: M S b S , Ph.D. Title of diploma thesis: Study and Evaluation of Topically Applied Ceramides onto Disrupted Skin Barrier Skin is the largest organ of the human body and serves several key functions, such as protection against external influences and regulation of body temperature. Healthy skin is able to maintain the integrity and stability of the organism due to its complex structure. The skin is composed of several layers of cells, including the stratum corneum (SC), which forms the main protective barrier. Ceramides (CER) are one of the main types of barrier lipids found in the SC. These lipid molecules, along with other lipids, create a hydrophobic matrix that protects the skin from dehydration and other external influences. The lack of CER in the skin barrier leads to the disruption of its function and the worsening of the skin condition. This is associated with many diseases, such as dermatitis, psoriasis, and others. The study of CER in the SC is important to understand the mechanisms of skin protection and to develop new therapeutic approaches for the treatment of skin diseases. Topical administration of barrier lipids, especially CER, is one possible treatment route for skin diseases. Therefore, the aim of this work was to prepare...
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The study of model lipid membranes containing omega-hydroxylated ceramides
Svatošová, Linda ; Opálka, Lukáš (advisor) ; Pullmannová, Petra (referee)
Charles University, Faculty of pharmacy in Hradec Králové Department of Organic and Bioorganic Chemistry Candidate: Linda Svatošová Supervisor: PharmDr. Lukáš Opálka, Ph.D. Title of diploma thesis: The study of model lipid membranes containing omega- hydroxylated ceramides Acylceramides (EO-Cer) belong to a class of ceramides (Cer) with an ultralong acyl chain whose ω-hydroxyl group is esterified with linoleic acid. The importance of EO-Cer lies in the formation of the long periodicity phase (LPP) and the corneocyte lipid envelope (CLE), which are indispensable components for the skin functioning as a barrier. Disorders in EO-Cer biosynthesis are associated with insufficient production of CLE and LPP leading to many skin diseases, including some types of ichthyosis. One of the enzymes that is deficient in such ichthyoses is PNPLA1. Insufficient function of this enzyme disables ω-esterification with linoleic acid, and thus the formation of EO-Cer. On the contrary, their precursors, i.e. ω-hydroxylated ceramides (O-Cer), are cumulated. The aim of this thesis was to prepare model membranes containing O-Cer and to study the effects of O-Cer on the lipid organization and barrier properties of model membranes. Within this thesis, two types of membranes were prepared - the first type were membranes...
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Study and Evaluation of Topically Applied Ceramides onto Disrupted Skin Barrier
Svobodová, Marie ; Kováčik, Andrej (advisor) ; Vraníková, Barbora (referee)
Department of Pharmaceutical Technology Author: M S b S , Ph.D. Title of diploma thesis: Study and Evaluation of Topically Applied Ceramides onto Disrupted Skin Barrier Skin is the largest organ of the human body and serves several key functions, such as protection against external influences and regulation of body temperature. Healthy skin is able to maintain the integrity and stability of the organism due to its complex structure. The skin is composed of several layers of cells, including the stratum corneum (SC), which forms the main protective barrier. Ceramides (CER) are one of the main types of barrier lipids found in the SC. These lipid molecules, along with other lipids, create a hydrophobic matrix that protects the skin from dehydration and other external influences. The lack of CER in the skin barrier leads to the disruption of its function and the worsening of the skin condition. This is associated with many diseases, such as dermatitis, psoriasis, and others. The study of CER in the SC is important to understand the mechanisms of skin protection and to develop new therapeutic approaches for the treatment of skin diseases. Topical administration of barrier lipids, especially CER, is one possible treatment route for skin diseases. Therefore, the aim of this work was to prepare...
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Study of Topical Ceramide Application
Kulhánková, Roksolana ; Kováčik, Andrej (advisor) ; Vraníková, Barbora (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Technology Author: Roksolana Kulhánková Supervisor: doc. PharmDr. Andrej Kováčik, Ph.D. Title of diploma thesis: Study of topically administred ceramides The human stratum corneum (SC) is the uppermost layer of the epidermis, which is made up of several layers of corneocytes. The space between the corneocytes is filled with barrier lipids, i.e., ceramides, cholesterol, and fatty acids, which are represented in an equimolar ratio. The arrangement of intercellular lipids has a significant effect on the barrier properties of the skin. Damaged skin barrier (e.g., in atopic dermatitis) is associated with a lack of lipids in the SC lipid matrix, which is reflected in increased trans-epidermal water loss and deterioration of skin quality (e.g., severe dryness, flaking, and cracks). One of the potential ways to restore the skin barrier is the topical administration of barrier lipids, especially ceramides (Cer). The goal of this work was to study the effect of topically administered Cer (very long-chain Cer AP alone or in combination with ultra-long-chain Cer EOS) on model-damaged SC and their effect in the process of restoring barrier function. Several topically administered formulations (creams) were prepared, which...
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Synthesis of ceramides derived from 6-hydroxysphingosine
Kavuljak, Juraj ; Opálka, Lukáš (advisor) ; Matouš, Petr (referee)
Title of the Master thesis: Synthesis of ceramides derived from 6-hydroxysphingosine Candidate: Juraj Kavuljak Supervisor: PharmDr. Lukáš Opálka, Ph.D. Consultant: Mgr. Veronika Ondrejčeková Charles University, Faculty of Pharmacy in Hradec Králové Skin Barrier Research Group, Department of Organic and Bioorganic Chemistry Ceramides (Cer), belong to the group of sphingolipids naturally found in each cell. One of their principal functions is cell signaling. We can find Cer in the uppermost layer of epidermis (stratum corneum), where the concentrations of these lipids are highest in the whole human body. Cer form an intercellular multi-lamellar lipid matrix. This lipid mass is composed of cholesterol and free fatty acids as well. The major function of stratum corneum is to protect the body from the excesive transepidermal water loss, provide internal homeostasis and create a protective barrier against harmful substances from external environment. Cer are amides of long aminoalcohols with a fatty acid attached to their primary amino group. 6-hydroxysphingosine (H) is specific for human epidermis, but its function and biosynthesis in skin is still not completly understood. Some studies showed lower concentrations of 6-hydroxysphingosine-based Cer in skin of patients suffering from atopic dermatitis....
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Study of Topical Ceramide Application
Kulhánková, Roksolana ; Kováčik, Andrej (advisor) ; Vraníková, Barbora (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Technology Author: Roksolana Kulhánková Supervisor: doc. PharmDr. Andrej Kováčik, Ph.D. Title of diploma thesis: Study of topically administred ceramides The human stratum corneum (SC) is the uppermost layer of the epidermis, which is made up of several layers of corneocytes. The space between the corneocytes is filled with barrier lipids, i.e., ceramides, cholesterol, and fatty acids, which are represented in an equimolar ratio. The arrangement of intercellular lipids has a significant effect on the barrier properties of the skin. Damaged skin barrier (e.g., in atopic dermatitis) is associated with a lack of lipids in the SC lipid matrix, which is reflected in increased trans-epidermal water loss and deterioration of skin quality (e.g., severe dryness, flaking, and cracks). One of the potential ways to restore the skin barrier is the topical administration of barrier lipids, especially ceramides (Cer). The goal of this work was to study the effect of topically administered Cer (very long-chain Cer AP alone or in combination with ultra-long-chain Cer EOS) on model-damaged SC and their effect in the process of restoring barrier function. Several topically administered formulations (creams) were prepared, which...
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Quantification of skin ceramides in patients after oncological treatment
Voláková, Eliška ; Opálka, Lukáš (advisor) ; Roh, Jaroslav (referee)
Charles University, Faculty of pharmacy in Hradec Králové Department of Organic and Bioorganic Chemistry Candidate: Eliška Voláková Supervisor: PharmDr. Lukáš Opálka, Ph.D. Title of diploma thesis: Quantification of skin ceramides in patients after oncological treatment Ceramides are one of the three basic lipid components present in the stratum corneum of human skin. Alterations in the ratio of individual ceramides are associated with disruption of skin barrier function. Such changes have been observed not only in skin diseases of the non-cancerous type, but also as a consequence of cancer. The main aim of the present study was to investigate the difference in the representation of skin ceramides in the stratum corneum of healthy patients and patients after cancer. Samples were collected from five groups of patients, four of which represented cancer patients with different types of treatment: tumor resection, chemotherapy, radiation or a combination of chemotherapy and radiation. The remaining fifth group consisted of control samples from volunteers without a diagnosis of cancer. Samples were obtained by tape-stripping from an identical site on patient forearm, followed by protein determination. Cancer patient samples were compared with control samples in terms of different water loss through the...
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Synthesis of modified and labeled acylceramides
Havrišák, Tomáš ; Opálka, Lukáš (advisor) ; Pour, Milan (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Organic and Bioorganic Chemistry Candidate: Tomáš Havrišák Supervisor: PharmDr. Lukáš Opálka, Ph.D Title of diploma thesis: Synthesis of modified and labeled acylceramides Upper most layer of skin, stratum corneum is providing effective barrier which protects us from impact of environment. Extracellular lipids of stratum corneum are mostly composed of ceramides, free atty acids and cholesterol. Earlier it was suggested that these lipids are highly rigid, which enables sufficient barrier function. But presently, it is known that some structural parts of these lipids are more fluid. So far, ultralong ceramides (also known as acylceramides), lipids which are necessary for correct barrier function still remain partly unexplored. Mobility of sphingosine part and linoleic ester have already been studied, but mobility of the ultralong chain is speculative. Obtaining information about mobility of particular parts of acylceramides is difficult because of their unavailability with required labelling. Our aim was to prepare acylceramides with deuterium-labelled half of their ultralong chain between carbons C17 - C32 from commercially available perdeuterated compounds. From available options we chose 1,12-dibromodocecane and...
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Optimization of the skin barrier model with isolated ceramides of human stratum corneum
Dulanská, Lucia ; Pullmannová, Petra (advisor) ; Zbytovská, Jarmila (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Biophysics and Physical Chemistry Author: Lucia Dulanská Supervisor: Mgr. Petra Pullmannová, Ph.D Title of thesis: Optimization of the skin barrier model with isolated ceramides of human Stratum corneum Stratum corneum (SC), the uppermost layer of the skin, regulates transcutaneous water loss and protects against outer conditions and harmful substances. It consists of cornified cells - corneocytes and extracellular lipid matrix, which is responsible for the barrier functions. Corneocytes are covered with covalently bound lipids creating the corneocyte lipid envelope (CLE). CLE is considered to interconnect the extracellular lipids with corneocytes and to have a templating effect. We aimed to optimize a skin lipid model simulating also the presence of CLE. The lipidic part of the model was prepared from an equimolar mixture of isolated human skin ceramides (hCer), cholesterol and free fatty acids (FFA, either protonated or deuterated) with 5 weight % of cholesteryl sulfate. hCer were extracted from the isolated human SC and purified by the column chromatography. The composition of hCer was determined by the high- performance thin-layer chromatography. The reverse-phase and normal phase silica gel particles served as the CLE...
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Study of free sphingoid bases in skin barrier
Jarešová, Zuzana ; Kováčik, Andrej (advisor) ; Vraníková, Barbora (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Technology Author: Zuzana Jarešová Supervisor: PharmDr. Andrej Kováčik, Ph.D. Consultant: PharmDr. Lukáš Opálka, Ph.D. Title of diploma thesis: STUDY OF FREE SPHINGOID BASES IN SKIN BARRIER The skin barrier, localized in the stratum corneum (SC), consists of corneocytes and an intercellular matrix formed from three types of lipids - ceramides, free fatty acids, and cholesterol, represented in an equimolar ratio. The overall arrangement of lipids is organized and highly specialized. Ceramides are structurally formed from the fatty acid acyl attached to a sphingoid base. In minor but not insignificant amounts, free sphingoid bases can also be found in the skin barrier. Several studies show that there is an increased concentration of free sphingoid bases in skin barrier disorders, such as atopic dermatitis. Although it is assumed that the presence of free sphingoid bases affects the skin barrier, it is not elucidated the way of their participation till today. The lack of studies or their diverse results leads us to the main goal of this thesis - to clarify how free sphingoid bases influence the skin barrier. In this work, the model membranes were prepared by the isolation of human SC ex vivo. Sphingosine (S),...
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