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V Ruocco

Publications and source records attributed to V Ruocco.

At least 37 records · Page 2Linked to original sources

Effects of gemfibrozil on in vitro cultured normal human skin explants.

BACKGROUND: Several lipid-lowering agents, when given topically, show a profound effect on skin morphology. Because of low bioavailability of these drugs for keratinocytes, the incidence is extremely low clinically. The most appropriate way to study the effect of hypolipidemic drugs on keratinocytes is by artificial exposure of the skin to high drug concentrations. OBJECTIVE: To study the effects of gemfibrozil on the morphology of in vitro cultured normal human skin explants. As gemfibrozil induces barrier disruption by inhibiting epidermal sterologenesis, essential for a competent permeability barrier, it is interesting to investigate the morphologic changes associated with this phenomenon. Studying the epidermal changes induced by lipid-lowering agents is important, not only because it might lead to a better understanding of the effects of these drugs on keratinocytes, but as it might also unlock the door to a wider knowledge of the pathomechanism of disorders of cornification. METHODS: Normal human skin from patients undergoing mastectomy was cultured in the presence of 2, 5, and 10 mM of gemfibrozil for 4 days The morphologic changes were evaluated by three blinded observers. Their reports were matched and collated. RESULTS: The cultured skin in the presence of gemfibrozil showed cell crowding of keratinocytes in the lower part of the epidermis, indicating epidermal hyperplasia and increased proliferation. Intercellular edema with the formation of small cavities in the epidermis, intracellular edema, and vacuolar alteration of keratinocytes in the upper portion of the epidermis were also observed. The intensity of these changes tended to parallel the gemfibrozil concentration. Some dermo-epidermal detachments did not correlate with the gemfibrozil concentration, but rather with tissue characteristics peculiar to each explant. CONCLUSIONS: The morphologic changes caused by gemfibrozil to normal human skin were not characteristic of psoriasis, and included intracellular and intercellular edema in the upper portion of the epidermis and cell crowding, indicating epidermal hyperplasia in the lower portion of the epidermis. The present experimental study gives further support to the hypothesis that hypolipidemic drugs cause an initial break in the barrier function of the epidermis, followed by a physiologic epidermal response, aimed at barrier restoration. This rather nonspecific stimulus to epidermal proliferation may trigger psoriasis in predisposed patients.

Cells, Cultured↗

Common human leukocyte antigen alleles in pemphigus vulgaris and pemphigus foliaceus Italian patients.

Pemphigus refers to a group of autoimmune blistering skin diseases, mainly identified as pemphigus vulgaris and pemphigus foliaceus, both characterized by the presence of autoantibodies against keratinocyte adhesion molecules, leading to loss of cell-cell adhesion with consequent blister formation. Pemphigus vulgaris is reported to be associated with human leukocyte antigen DR4 and/or DR6 whereas no data are available on pemphigus foliaceus, except for the endemic Brazilian form (fogo selvagem), which is reported to be associated with DR1 and DR4. We here report human leukocyte antigen molecular typing on a total of 87 patients, 61 with pemphigus vulgaris and 26 with pemphigus foliaceus, versus 128 healthy matched controls. Generic typing showed an increase of DRB1*04 and DRB1*14 and a decrease of DRB1*07 in both pemphigus vulgaris and pemphigus foliaceus patients. Molecular subtyping of DR4+ and DR14+ subjects showed a highly significant association between the DRB1*1401 and both pemphigus vulgaris (p < 0.0001) and pemphigus foliaceus patients (p < 0.0001) together with a significant increase of the linked DQB1*0503 (pemphigus vulgaris p < 0.0001; pemphigus foliaceus p < 0.0001). Moreover, whereas the association between DRB1*0402 and pemphigus vulgaris (p < 0.0001) has been confirmed, no significant association between a specific allele of the DR4 group and pemphigus foliaceus, has been found. Therefore, at least in Italian patients, pemphigus vulgaris and pemphigus foliaceus share DRB1*1401 and DQB1*0503, as susceptible human leukocyte antigen alleles, whereas DRB1*0402 is only found associated with pemphigus vulgaris. The observation that both diseases, pemphigus vulgaris and pemphigus foliaceus, carry the same susceptible human leukocyte antigen alleles has been interpreted as a common genetic background predisposing to pemphigus as, like in other autoimmune disorders, it is not sufficient to explain the onset of the disease on the basis of the sole aforementioned alleles. Other linked genes and/or environmental factors should play a facilitating role in the outbreak of pemphigus, either pemphigus vulgaris or pemphigus foliaceus.

Alleles↗

Different patterns of in vitro acantholysis in normal human skin samples explanted from different sites of the body.

BACKGROUND: The factors that contribute to a preferential anatomic localization of pemphigus lesions are not well known. In particular, the question arises as to whether certain skin areas may be more acantholysis-prone than others. OBJECTIVE: To verify whether, in pemphigus patients, a different susceptibility to acantholysis exists among different cutaneous regions, the technique of tissue cultures was used. METHODS: Normal human skin explants from two distinct anatomic regions (back and buttocks) of two former pemphigus patients were cultured in vitro in the presence of enalapril (6 mM) or cystamine (10 mM), two substances with a proven biochemical acantholytic effect. After 4 days of culture, the tissues were processed for standard histology. RESULTS: Diffuse acantholysis, with large intraepidermal splits, was observed in the explants taken from the backs of both subjects and cultured with either enalapril or cystamine. Mild to moderate acantholytic changes were detected in the explants taken from the buttocks of both subjects and cultured with either enalapril or cystamine. No structural changes were seen in the control cultures. CONCLUSIONS: Pemphigus patients present different thresholds of acantholysis in different areas of their bodies. This might explain, at least in part, certain preferential anatomic localizations of pemphigus lesions.

Acantholysis↗

Vitamin E: the radical protector.

Since its discovery and isolation the importance of vitamin E in maintaining normal physiologic processes and its value in treating various disease states have been the subject of much controversy. It was our intention to review and highlight some of the arguments and problems regarding the usefulness of vitamin E and to try to put them into proper perspective. The major area of interest concerning vitamin E lies essentially in its role in preventing damage caused by free radicals. The latter are now known to play an important role in radiation induced carcinogenesis, photoaging and photosensitization. The chemistry of vitamin E, its physiological function as a major antioxidant and its interaction with other antioxidants are described by the sum of animal studies, in vitro research and epidemiological investigations. In preparing the current data, it appeared that despite the controversy and conflicting results the body of literature as a whole judges vitamin E to be useful as an antioxidant. Although, in principle, the use of vitamin E can be quite advantageous, the manner of its administration, especially regarding topical application, remains unclear.

Animals↗

Gaining more insight into the pathomechanisms of thiol-induced acantholysis.

Acantholysis is considered the initial and the main pathogenetic event of pemphigus. The first step in drug-induced acantholysis (biochemical and/or immunological) involves binding of the drug to the cell membrane and the formation of 'drug-cysteine' instead of 'cysteine-cysteine' bondings. We suggest that the reaction of D-penicillamine with cystine disulfides that results in cysteine-penicillamine disulfides is not a terminal reaction, but rather a primary initiating step of a chain reaction. It is reasonable to consider that the cysteine-penicillamine disulfide is continuing to be enzymatically reduced by various thiol reductants, in particular glutathione reductase, thereby generating a 'new' penicillamine molecule which, in turn, reacts with other cystine disulfides and does so in an unending cycle. A chain reaction is thus created in which the drug is repeatedly generated so that one molecule of the drug may attack thousands of cystine disulfide bonds. It is highly possible that normal individuals have their own endogenous means of controlling this deleterious chain reaction, whereas pemphigus-prone individuals lack the ability to stop this potentially damaging reaction. Drug-induced pemphigus should thus be added to the ever-growing list of adverse drug reactions related to pharmacogenetic disorders in drug metabolism.

Acantholysis↗

Oral pemphigus: clinical significance of esophageal involvement: report of eight cases.

The extension of the blisters of pemphigus to the esophagus is relatively uncommon, especially in patients treated with corticosteroids who appear to be in clinical remission. The aim of this study was to evaluate the esophagus in eight patients affected by oral pemphigus in various stages of the disease. Upper gastrointestinal endoscopy revealed esophageal involvement in five patients (two men and three women); three had blisters or erosions in the upper esophagus, whereas two showed red longitudinal lines along the entire organ. Direct immunofluorescence was positive in all eight patients. It is suggested that endoscopic examination of esophageal mucosa is an objective criterion by which to judge the success of therapy of pemphigus vulgaris.

Adrenal Cortex Hormones↗

The in vitro effect of hydroxychloroquine on skin morphology and transglutaminase.

BACKGROUND: Antimalarials are some of the most notorious drugs which may induce psoriasis, with 25% of all reported cases being associated with them. Antimalarials do not induce psoriasis de novo, but trigger subclinical psoriasis. In a previous report, we suggested that antimalarials exert their effect by interfering with the epidermal transglutaminase (TGase) activity. OBJECTIVE: To verify this hypothesis by examining the effect of hydroxychloroquine sulfate (HCQS) on cultured human skin and on TGase activity in vitro. MATERIALS AND METHODS: Skin samples from normal donors were cultured in the presence of HCQS for 4 days, and then processed for microscopic examination. TGase activity was assayed in the presence of HCQS and compared with blanks. RESULTS: Significant changes in epidermal morphology were seen in all explants cultured in the presence of HCQS at all concentrations employed. Areas of enhanced and irregular keratinization were observed in the upper epidermis, while a loss of cell polarity, with keratinocyte crowding and disarray, was seen in the lower epidermis. In addition, we observed intraepidermal splitting at different levels and dermo-epidermal detachments. HCQS showed a concentration-dependent inhibition of TGase activity. CONCLUSIONS: We suggest that HCQS causes an initial break in the barrier function of the epidermis by inhibiting TGase activity; this is followed by a physiologic response of the epidermis aimed at barrier restoration. This rather nonspecific stimulus to epidermal proliferation is probably sufficient to trigger psoriasis in predisposed individuals or aggravate it in psoriatic patients.

Antimalarials↗

Isotopic response.

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Herpes Zoster↗

Immunocytochemical detection of autoantibody deposits in Tzanck smears from patients with oral pemphigus.

Eighteen patients, ten affected by pemphigus vulgaris and four affected by herpes simplex of the oral mucosa, together with four healthy patients as controls, were investigated by cytologic examination of Papanicolaou stained smears obtained by scraping the oral mucosa. In all cases additional smears were immunostained with the alkaline phosphatase-anti-alkaline phosphatase (APAAP) technique using monoclonal antibodies against human heavy IgG chains and lambda light chains. The results have shown that, for a cytological diagnosis of pemphigus, this technique can be used as an easy substitute for the immunofluorescence test and does not require any specialized training or equipment. The findings are clearly detectable by light microscopy and allow, together with the immunostaining, an adequate visualization of cell morphology.

Adult↗

Antiviral therapy for recurrent herpes simplex reconsidered.

The purpose of this paper is to present our long-time concern about the safety of using antiherpetic drugs over extended periods of time as a preventive therapy for recurrent herpetic attacks. It has been shown that when herpes simplex virus (HSV) is inactivated and has thus lost its cytolytic activity by exposure to certain chemicals or ultraviolet irradiation, it can cause neoplastic changes in mammalian cells. Therefore, substances that inhibit (but not absolutely eliminate) HSV replication for prolonged periods of time might be of potential danger for the development of cancer. It becomes incumbent upon us to ask ourselves whether the prolonged inhibitory effect of prophylactic antiviral drugs might not carry with it the same risks as has been proposed for other substances known to inhibit viral replication.

Animals↗