Occlusive treatment in psoriasis: how does it work?
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Biomedical subjects
Publications and source records attributed to T Lotti.
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BACKGROUND: Alopecia areata (AA) is a noncicatricial alopecia with still unknown pathogenesis, but increasing evidence suggests that an immunologic process might be responsible for the disease. MATERIALS AND METHODS: Nineteen patients with AA were studied with ten of them in the progressive phase of the disease and nine in the stabilized phase. Biopsies of both affected and unaffected skin were taken. For immunohistochemistry, monoclonal antibodies directed against CD3, CD4, CD8, CD10a, CD36, and HLA-DR antigens, were used, as well as antibodies directed against adhesion molecules ICAM-1, ELAM-1 and LFA-1. For electron microscopy (EM), specimens were fixed in glutaraldehyde-sodium cacodylate buffer, post-fixed in osmium tetroxide, and stained with uranyl acetate. For statistical analysis, sections from involved and uninvolved skin of each patient for each antibody, the sign test, Fisher's F-test, and the Tukey-Kramer test were used. RESULTS: There was a rich infiltrate of CD4+ cells and CD1a+ cells, particularly in the perivascular zone of both unaffected and affected skin (here in the perivascular and in the peribulbar zone) in the progressive phase of AA. In the stabilized phase the infiltrate was scant, both in unaffected and affected skin and limited to the peribulbar area. Receptors of adhesion molecules (ICAM-2, ELAM-1, LFA-1) were strongly expressed, mainly at the microvascular level in both unaffected and affected skin in the progressive phase, but were only weakly or not at all expressed in the stabilized phase, again in unaffected and affected skin. Ultrastructural data confirmed the immunohistochemical findings and showed close contacts between infiltrating lymphocytes and Langerhans'-lineage cells mainly in the progressive phase. CONCLUSIONS: Our results suggest that: 1) an immunologic process, apparently carried out by CD4+ lymphocytes and by dendritic CD1a+ and CD36+ cells, may play a key role at least in the early phase of the disease involving primarily microvessels and later on the bulbar area; 2) the expression of adhesion molecule receptors is involved at the beginning of the disease by mediating the adherence of leukocytes to endothelial cells and subsequent trafficking into the dermis.
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Cyclosporine A (CyA), a well established treatment of psoriasis, is a highly lipophilic cyclic undecapeptide mainly used for its immunosuppressive properties and exerting a wide spectrum of biological activities including fungicidal antiproliferative and anti-inflammatory effects. Plasminogen activators (PA), urokinase (UK, M(r) 55,000) and tissue type plasminogen activators (tPA, M(r) 74,000), physiologically catalyze the conversion of the plasminogen to the wide spectrum proteinase plasmin. UK and tPA are involved in cell growth, differentiation and migration. It has recently been shown that psoriatic epidermis is provided with abnormal tPA-dependent PA activity and that in lesional epidermis elevated tPA mRNA levels are present. It has been suggested that the tPA-dependent PA activity is a marker of disease activity and is reversible with different topical and systemic treatments. In this preliminary study we investigate the effect of CyA on the tPA mRNA transcription on A431 keratinocytes cell line. Subconfluent A431 cell cultures have been treated with CyA at in vivo relevant concentrations (10, 7.5, 5 micrograms/ml) for 48 h. Northern blot analysis of total RNA extracted from cultured A431 cell line has been performed for detecting tPA mRNA. mRNA for tPA has been detected in the control samples whereas an evident decrease of tPA mRNA expression has been detected in the CyA-treated samples. These data suggest that CyA could have an effect in clearing psoriatic lesions also modulating the abnormal plasminogen activation i.e. tPA-dependent serinoproteinase activity.
A group of 25 patients with uncomplicated BPH was treated mepartricin 150,000 U (40 mg) once in the evening for 60 days and the results were compared with those obtained in 25 patients treated with mepartricin 50,000 U (13 mg) t.d.s. Efficacy and tolerance of both treatment schemes were good. In the group treated with on single dose at night some symptoms such as nocturia and pollakiuria regressed more rapidly.
Several, more or less successful, medical treatments have been proposed for idiopathic male infertility. We assessed the effect of high-dose FSH (150 IU) in patients with idiopathic oligospermia in comparison with patients given low doses. In the high-dose group, there was a significant rise in spermatozoid concentration (p < 0.0001), mobility (p < 0.0001) and morphology (p < 0.007).
The authors assessed the validity of a treatment with mepartricin in BPH at the dose of 150,000 U in a once-a-day evening administration for 6 months. The results from the controlled study were compared with those obtained in a homogeneous group of patients treated with placebo. The analysis of the data obtained would suggest a preferential opinion in favour of the group treated with mepartricin which was effective in improving the symptomatology. Some hypothesis are put forward to interpret the results.
The tunica albuginea (TA) of the penis is thought to play a major role in the erection mechanism. It functions by compressing the subalbugineae venulae, which promotes the slower venous flow during erection, and provides a fibrous frame to give an inextensible support for the vessels and nerves. It acts as the inextensible enclosing structure which contains the erectile tissue and gives the erect penis its shape. The functions of the TA result from its structure, consisting for the most part of collagenic and elastic fibers. This study investigated, with the aid of scanning electron microscopy (SEM), the microarchitecture of the TA and the spatial relation of its fibers in ten impotent patients and in six control subjects with normal erectile function. The arrangement of elastic fibers in the TA seems to account for their function, which is to prevent the overstretching of collagenic fibers during maximum intracavernous pressure. In impotent patients, a reduction in the elastic fibers in the TA appears to produce disorders in the arrangement of the collagenic fibers. These alterations in the architecture of the TA in impotent patients can give rise top erection disorders.
Neuropeptides are a heterogeneous group of more than 50 molecules that play a role in various cutaneous functions and diseases; they act as neuromodulators, neurotransmitters, neurohormones, and hormones. In the skin, neuropeptides are synthesized locally (i.e., in keratinocytes and in endothelial cells) and are transported by nerve fibers or immune cells (i.e., lymphocytes, monocytes, and polymorphonuclear cells). Specific receptors and binding sites for neuropeptides have been described in different cell lines in the skin (keratinocytes, endothelial cells, immune cells, fibroblasts). Many different biologic actions of neuropeptides have been demonstrated. Depletion of cutaneous neuropeptides (i.e., with capsaicin cream) or therapeutic use of neuropeptide agonists and/or antagonists may aid in the treatment of skin diseases.
BACKGROUND: Adhesion molecules play a major role in the pathogenesis of inflammatory skin diseases by regulating lymphocyte trafficking and homing in an inflamed area. METHODS: The expression of the lymphocyte function-associated antigen-1 (LFA-1) and of its ligand, the intercellular adhesion molecule-1 (ICAM-1) has been studied in psoriatic skin lesions of 10 patients with guttate, nummular, and palmoplantar psoriasis. In addition, the peculiar immunophenotype of infiltrating cells (CD3, CD4, CD8, CD25) and their correlation with HLA-DR expression before and after treatment with oral cetirizine, a highly selective, third generation H1-receptor antagonist has been examined using the labeled avidin biotin (LAB) system. RESULTS: Cetirizine treatment modulated in vivo the expression of adhesion molecules LFA-1/CAM-1 as shown in all cases by decreased levels of their expression on keratinocytes and on dermal endothelial cells (P < 0.001). The expression of HLA-DR on keratinocytes and endothelial cells was also inhibited after treatment. The numbers of infiltrating CD3-, CD4-, CD8-positive cells were reduced, whereas there was no significant modification of CD25-positive cells within the epidermis and the dermis. CONCLUSION: This open clinical trial suggests that cetirizine could be effective in treating psoriasis: (1) for its symptomatic control on itching; (2) for its immunopharmacologic modulation of leukocyte integrins and on the immunophenotype pattern of infiltrating and resident cells, and (3) for contributing to the clearing of the lesions clinically.
BACKGROUND: Progressive pigmented purpura (Schamberg's disease), a form of purpura pigmentosa chronica, is a lymphocytic capillaritis of unknown etiology and obscure pathogenesis. Our purpose was to assess the expression of cell membrane antigens (CD3, CD4, CD1a, CD36), of adhesion receptors (leukocyte function adhesion 1, LFA-1, endothelial leukocyte adhesion molecule 1, ELAM-1) intercellular adhesion molecule 1, ICAM-1), and the intercellular relationships in the early phase of the disease. METHODS: Quantitative immunohistochemistry and electron-microscopy were performed on specimens of five subjects, aged 45 to 63 years. These studies were repeated in two patients after treatment with topical corticosteroid (betamethasone valerate cream 0.1%) and psoralen-ultraviolet A (PUVA). RESULTS: The infiltrate consisted mainly of CD4+ lymphocytes and CD1a+ dendritic cells. Electron-microscopic investigation showed typical lymphocytes and two distinct types of dendritic cells. In the very early phase of the disease the adhesion receptors LFA-1 and ICAM-1 were expressed intensely by all infiltrating cells; the adhesion receptors ICAM-1 and ELAM-1 were expressed by endothelial cells. Close contact occurred between lymphocytes and dendritic cells. After PUVA (120 J per cm2) and topical steroid therapy the infiltrate disappeared completely. CONCLUSIONS: These data suggest that a cell-mediated immune mechanism may be important in progressive pigmented purpura and that the early endothelial expression of adhesion receptors may determine the pattern of organization of the pericapillary infiltrate.
BACKGROUND AND OBJECTIVE: The pathogenesis of leg ulcers due to chronic venous hypertension (CVH) seems to be related to perivenular fibrin-film formation due to decreased cutaneous fibrinolytic activity dependent on reduced release of tissue-type plasminogen activator that leads to tissue anoxia and ulcer formation. The purpose of the work is a spectrophotometric evaluation of urokinase (UPA) at the edge, the floor and in the periulcerous skin of leg ulcers. METHODS: We examined a group of 10 patients with chronic leg ulcers caused by CVH. The biopsies from each patient were taken: (1) from the edge of the ulcer; (2) from the perilesional skin and (3) from the floor of the ulcer. Urokinase levels were evaluated in the same areas in 10 control subjects. The UPA activity was determined spectrophotometrically at 405 nm. RESULTS: The results of our study showed that UPA is detectable in the center of the ulcer, on the edge, in the perilesional skin, as well as in the controls. Data are statistically significant. The highest levels of UPA are found at the edge of the ulcer; they were lower in the center and in the periulcerous skin. CONCLUSION: A chemoattracting effect of UPA on human keratinocytes has been documented and this study showed significantly higher levels of UPA at the edge and on the floor of the ulcers, suggesting a possible role of an UPA gradient that could promote mobilization of keratinocytes from the edge to the floor, thus inducing reepithelialization. Moreover, UPA could play some role in neoangiogenesis and fibroblast chemoattraction, thus contributing in various ways to wound healing.
The tunica albuginea of the corpus cavernosum provides the latter with a fibrous framework and plays a significant role in erectile function. Being rich in elastic fibres the tunica albuginea is able to resist overstretching of the corpus at raised levels of intracavernous pressure, compressing the sub-algunineum venous reticulum and promoting the maintenance of erection. Results are reported here on assessment of the concentration of elastic fibres in tunica albuginea in relation to frequency of nocturnal erection, tumescence and penile length and rigidity. Significant correlations were demonstrated between concentration of elastic fibres and duration of nocturnal erection (P< 0.0001), rigidity at TIP(P< 0.001), and rigidity at BASE (P< 0.001). The importance of the structural soundness of the tunica albuginea for achievement of satisfactory erection was thereby underlined.
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Vasculitis is defined as angiocentric segmental inflammation of the blood vessels and fibrinoid necrosis of the vessel wall. Classification of vasculitis is a controversial problem, because of the difficulty in incorporating globally different criteria such as histologic features, size of affected blood vessels, etiology, pathogenesis and other factors in a single classification schema. In this paper we review the principal classifications and make a novel attempt to classify vasculitis on the basis of the size of affected vessels. We hope that a new generation of basic and clinical investigators can achieve a better understanding of the pathogenesis of various vasculitis-related syndromes and that this understanding will facilitate future classification schemas.
Cutaneous necrotizing vasculitis (CNV) have been traditionally divided into "leukocytoclastic" and "lymphomonocytic" forms. The etiology and the pathogenesis of the two forms are not clear. We studied by immunohistochemistry and electronmicroscopy the infiltrate of 5 cases of leukocytoclastic form and 5 cases of lymphomonocytic form of CNV in two phases (early and late). Aim of the study was to evaluate: 1. the immunophenotypical characteristics of the infiltrate; 2. the expression of some adhesion molecules receptors; 3. the ultrastructural characteristic of the infiltrate; 4. the possible sequence of the events. Our results showed, by immunohistochemistry, a rich infiltrate of CD3+, CD4+, CD1a+ cells in both phases of lympho-monocytic vasculitis and a poor infiltrate of CD4+, CD1a+ and CD36+ cells in the early phase of leukocytoclastic vasculitis, while the perivascular infiltrate was rich of these cells in the late phase of this latter form. ICAM-1 and LFA-1 were strongly expressed in lympho-monocytic vasculitis. By electronmicroscopy, most infiltrating cells showing the ultrastructural markers of immature cells of dendritic lineage were in contact with each other and with lymphocytes and perivascular dendritic macrophages in lymphocytic form and in the late phase of leukocytoclastic form. Our results suggest that lymphocytic vasculitis might be related to a cell-mediated immune reaction and that the leukocytoclastic form of CNV, formerly considered a typical neutrophilic disease, is also maintained by a cell-mediated immune response to not yet identified endogenous antigens released in the lesional area.
Langerhans cells are members of the dendritic cell system, which reside in the skin. These cells have many immunohistochemical and ultrastructural markers (for example, they are CD1a+ and possess Birbeck granules), which consent to identify them in an infiltrate. Langerhans cells have the specific role to present the antigens to T lymphocytes and to induce the cell-mediated immune reaction. Cutaneous necrotizing vasculitis (CNV) can be divided in two major forms: a leukocytoclastic type and a lymphocytic type. The pathogenesis of the first one is presumably immune complex-mediated, while for the second one a cell-mediated immunity has been proposed. Our group investigated on the cell infiltrate of some cases of CNV, both leukocytoclastic and lymphocytic type; and for leukocytoclastic CNV two phases were studied: an early one (at the onset of the lesion) and a later one (more than 24 hours). Special attention was paid to the presence of dendritic cells in the infiltrate and to their relationship to lymphocytes, if present. By immunohistochemistry and electron microscopy we could find many Langerhans cells and T lymphocytes in lymphocytic and in the late phase of leukocytoclastic CNV. The observed pattern of the cell infiltrate suggests that a cell mediated immune response play a major role in the pathogenesis of lymphocytic vasculitis and that dendritic cells and lymphocytes contribute to self-perpetuate leukocytoclastic vasculitis, which cannot be anymore considered as simply due to infiltration of neutrophils.