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An introduction to skin and skin disease
Published in Rashmi Sarkar, Anupam Das, Sumit Sethi, Concise Dermatology, 2021
The cells of the epidermis are mainly keratinocytes containing keratin tonofilaments, which originate in the basal generative compartment and ascend through the Malpighian layer to the granular cell layer. The keratin tonofilaments belong to the group of subcellular structures known as intermediate filaments. They consist of polypeptides and their molecular weight ranges from 40 to 65 kD. It is thought that they provide a semi-rigid endoskeleton, and because of their connection to the desmosomal apparatus, they give strength to the epidermis as a whole. They are joined to the neighbouring keratinocytes by specialized junctions known as desmosomes. These are visible as ‘prickles’ in formalin-fixed sections but as alternating light and dark bands when viewed by transmission electron microscopy. In the granular layer, they transform from a plump oval or rectangular shape to a more flattened profile and lose their nucleus and cytoplasmic organelles. In addition, they develop basophilic granules containing a histidine-rich protein known as filaggrin and minute, lipid-containing, membrane-bound structures known as membrane-coating granules of lamellar bodies.
An introduction to skin and skin disease
Published in Ronald Marks, Richard Motley, Common Skin Diseases, 2019
The cells of the epidermis are mainly keratinocytes containing keratin tonofilaments, which are born in the basal generative compartment and ascend through the Malpighian layer to the granular cell layer. The keratin tonofilaments belong to the group of subcellular structures known as intermediate filaments. They consist of polypeptides and range in molecular weight from 40 to 65 kD. It is thought that they provide a semi-rigid endoskeleton and because of their connection to the desmosomal apparatus give strength to the epidermis as a whole. They are joined to neighbouring keratinocytes by specialized junctions known as desmosomes. These are visible as ‘prickles’ in formalin-fixed sections but as alternating light and dark bands when viewed by transmission electron microscopy. In the granular layer, they transform from a plump oval or rectangular shape to a more flattened profile and lose their nucleus and cytoplasmic organelles. In addition, they develop basophilic granules containing a histidine-rich protein known as filaggrin and minute lipid-containing, membrane-bound structures known as membrane-coating granules or lamellar bodies.
Cells in Lymph
Published in Waldemar L. Olszewski, Lymph Stasis: Pathophysiology, Diagnosis and Treatment, 2019
Histology of the skin showed typical changes of hyperkeratosis, abundant fibroblasts, dense bundles of collagen fibers, and infiltrates (see Figure 20) of lymphatic “lakes” with borders not lined by cells. These “lakes” (see Figure 21) were empty of cells but did contain proteinaceous fluid. The same kit of moabs (monoclonal antibodies) was used for labeling skin as for lymph cells, but only some skin cell populations were stained with antibodies which stained lymph cells; others remained negative. Few mononuclear cells with microscopic appearance of lymphocytes, including those in perivascular infiltrates, were CD3 positive. Some scattered CD4- and CD8-positive cells were seen in the Malpighian layer of skin. Also, no B (CD19), transferrin, C3bR, and IL 2-R-positive cells were detected. This arrangement is in keeping with patterns described for normal skin. The CD 1-positive cells were found in epidermis in greater numbers than in healthy epidermis (see Figure 22), with some around skin blood vessels.
Nanotechnological interventions in dermatophytosis: from oral to topical, a fresh perspective
Published in Expert Opinion on Drug Delivery, 2019
Riya Bangia, Gajanand Sharma, Sunil Dogra, Om Prakash Katare
The viable arthrospores or hyphae get deposited on the surface of the vulnerable individual. After the introduction in the skin of host, certain suitable conditions cause the infection to establish and progress through the stages known as adherence, penetration, and retention. The myriad mechanisms and host factors, including the ability to adapt to human body, number and activity of sebaceous glands in a particular region of the body (as sebum exhibits an inhibitory effect on dermatophytes), break in the skin barrier, macerated skin and increased hydration can enable certain fungi to adhere to particular host [17]. There is not much information available related to the factors that facilitate the adherence of dermatophytes. However, it has been hypothesized that proteases secreted by dermatophytes mediate their adherence. T. rubrum is able to adhere to epithelial cells due to carbohydrate-specific adhesins expressed on the surface of arthroconidia (infectious agent) [18]. After the arthroconidia adhere to the keratinized tissue, their germination and growth progress radially in multiple directions [18,19]. The proteases in the dermatophytes aim at digesting the network of keratin to oligopeptides or amino acids. After establishment, the spores germinate and penetrate the stratum corneum layer. This penetration is accompanied by the keratinases found in the dermatophytes. The metabolic products of fungi diffuse through the malpighian layer leading to responses in the form of erythema, vesicle formation, and pruritis [17]. The penetration is followed by the retention phase in which after the stratum corneum is invaded and infected by the dermatophytes, they reside in this layer and hardly penetrate beyond the epidermal surface and its appendages [20].
Guselkumab for the treatment of palmoplantar pustulosis
Published in Expert Opinion on Biological Therapy, 2020
The pathomechanism/pathogenesis of PPP remains unclear; there have been few relevant reports, in part because of the lack of any animal model. The existing data were derived from human histopathological examinations, blood tests, and trial results. Several histopathological studies have suggested that the acrosyringium may be involved in PPP [22,23]. Lesions initially show unilocular vesicle formation in the lower Malpighian layer, followed by the development of a granular layer and orthokeratosis above the vascular space. Pustules then fill the unilocular space that contacts the neutrophil-rich stratum corneum. Histologically, the shoulders of well-delineated pustules resemble those of the micro-pustules of Kogoj often evident in generalized PP [24,25]. The antimicrobial peptide hCAP-18/LL-37 contributes to PPP pathogenesis: vesicular LL-37 inflames lesional skin[26]. TLN-58, derived from hCAP18, is present in skin PPP lesions [27]. This antimicrobial peptide contributes to neutrophil recruitment to lesional skin and also upregulates the production of proinflammatory cytokines in surrounding lesional keratinocytes, thus inducing inflammation. The proinflammatory cytokines involved in PPP have been explored in a small number of patients [28]. The mRNAs encoding IL-17, IL-22, IL-23, and IL-8 were upregulated in lesional skin compared to healthy control skin [28]. IL-8 is a major chemokine implicated in a number of inflammatory diseases characterized by neutrophil activation; thus, IL-8 may thus be critical in the pustulation of PPP lesions [29,30]. A phase 2 clinical trial of HuMab 10F8, a novel, fully human monoclonal antibody binding to a discontinuous IL-8 epitope that overlaps the receptor-binding site, thus effectively neutralizing IL-8-dependent human neutrophil activation and migration, concluded and represented a great step forward[30]. The drug significantly reduced clinical disease activity, with a ≥ 50% reduction seen in fresh pustule formation. IL-8 thus plays a critical role in PPP. However, no phase 3 trial has been performed.
Nanocrystal: a novel approach to overcome skin barriers for improved topical drug delivery
Published in Expert Opinion on Drug Delivery, 2018
Viral Patel, Om Prakash Sharma, Tejal Mehta
Epidermis forms the outermost layer of the skin, which is broadly divided into different layers, stratum corneum, stratum lucidum, stratum granulosum, stratum spinosum, and stratum germinativum [28]. The outermost covering of the epidermis is made up of dead cells, known as corneocytes, which have lost their cellular components including nucleus due to the deposition of protein, keratin. Corneocyte are tightly arranged; thus, they act as a major barrier restricting the entry of foreign particles/materials through the skin [29]. This layer of epidermis is known as stratum corneum. The stratum corneum is having protein bricks and lipid mortar-like structure. The protein bricks are created by the crosslinking of proteins through disulfide bond surrounding the corneocytes providing biomechanical strength [30]. While the lipid mortar plays a significant role as a functional barrier. The stratum corneum is much thicker in some parts of the body. The skin surface of palms of hand and foot soles bear vertically stacked corneocytes with average thickness of 400–600 µm and are known as stratum lucidum. The keratinocytes in this layer are dead, densely packed, transparent in appearance and provide barrier to water. The keratinocytes gradually become flatter, their cell membrane thickens, and the protein keratin gets accumulated as lamellar granules within the cells. This layer containing granular cells is called as stratum granulosum. Below stratum granulosum lies the stratum spinosum. This layer appears spiny due to protruding cell structures called desmosomes. The desmosomes create an interlock with each other, thereby strengthening the bond between the adjacent cells. Keratin and water repelling glycolipid which prevents water loss through skin are synthesized by the keratinocytes present in the stratum spinosum. The deepest layer of epidermis is stratum germinativum. The cells in this layer form bonds with dermis by intertwining with collagen fiber. It is composed of one to two layers of basal cells. These basal cells are precursors of keratinocytes and hence are stem cells with cuboidal shape. As new cells are formed by mitosis, the existing keratinocytes are pushed superficially toward the stratum corneum. The basal and the spinous cells are collectively called as Malpighian layer [29,31–35].