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Biomedical subjects

V Ruocco

Publications and source records attributed to V Ruocco.

At least 55 records · Page 3Linked to original sources
PubMed1996

Are acantholysis and transglutaminase inhibition related phenomena?

BACKGROUND: The loss of intercellular cohesion among keratinocytes (acantholysis) may be considered the histologic marker of pemphigus. Many drugs, especially thiol drugs, proved to be able to provoke in vitro acantholysis by biochemical mechanisms interfering with the disulfide and thiol group balance. As to nonthiol drugs, the pathomechanism of acantholysis is still unexplained. OBJECTIVE: To explain the molecular mechanism of enalapril-induced acantholysis a potential link between transglutaminase (TGase) activity and the effects of this drug was investigated. METHODS: TGase activity in extracts from human breast skin cultured in the presence of thiopronine, captopril and enalapril were evaluated in vitro. The acantholytic potential of cystamine, a known TGase inhibitor, was also investigated. RESULTS: Enalapril, the most powerful acantholytic drug in vitro, was found to inhibit both the purified enzyme and the TGase activity in the extracts from cultured human breast skin explants. Kinetic studies showed that enalapril inhibition was competitive with respect to the amino acceptor substrate and uncompetitive with respect to the amino donor substrate. Moreover, an acantholytic effect of cystamine on explants of normal human skin was shown. CONCLUSIONS: These results suggest that acantholysis and the inhibition of TGase activity could be two related phenomena.

Acantholysis↗
PubMed1996

A case of diet-related pemphigus.

An experimental investigation has lately shown that certain allyl compounds of garlic are able to provoke acantholysis in normal human skin cultured in vitro. The acantholytic effect has been more prominent in the samples from DR4+ donor. We here report a case of superficial pemphigus which appeared spontaneously in a DR4,14+, 49-year-old man and which ran a course that proved to be affected by dietary factors, in particular by the consumption of garlic. In the absence of a conventional treatment and on a garlic-free diet only, the disease ceased for several months. Soon after an unintentional dietary test with a strongly and presumable garlic-spiced fish meal, the pemphigus recurred. Nutritional factors should be added to the ever-growing list of exogenous factors capable of inducing or perpetuating pemphigus in genetically predisposed individuals.

Diet↗
PubMed1996

[Keratoacanthoma centrifugum marginatum. Possible etiological role of papillomavirus and therapeutic response to etretinate].

INTRODUCTION: Keratoacanthoma centrifugum marginatum is an uncommon keratoacanthoma of unknown etiology. We report a case suggesting a possible etiological role for a papillomavirus. Etretinate was an effective treatment. CASE REPORT: A 65-year-old woman had keratoacanthoma centrifugum marginatum of the antero-inferior aspect of the lower third of the right leg for 5 years. Fifteen years earlier, an infection had occurred at the same site after a trauma and was treated by oral antibiotics. Surgical exeresis was difficult due to the wide spread of the lesion. Etretinate given at an initial dose of 1 mg/kg/d for 6 weeks then reduced by half for 2 months led to nearly complete cure. DISCUSSION: Keratoacanthoma centrifugum marginatum, verrucous carcinoma and epidermal carcinoma have some histological characteristics in common, suggesting a possible common etiological agent which could be certain strains of the human papillomavirus (HPV). In our case etretinate provided cure, possibly due to its antitumoral activity and perhaps due to its antiviral activity. The presence of koilocytes suggested HPV infection which was confirmed by PCR. This test does not however provide proof of the etiological role of HPV. We are currently studying the presence of HPV in keratoacanthomas and their possible etiological role.

Aged↗
PubMed1995

Early diagnosis of multiple hamartoma and neoplasia syndrome (Cowden disease). The role of the dentist.

A typical case of Cowden disease is presented. This is rare mucocutaneous disease, genetically determined, with multiple organ system involvement in which a malignancy, particularly of breast and thyroid gland, may develop. The disease can be diagnosed in its early stages by gingival and cutaneous manifestations. We emphasize that the dentist may be the first health care professional who recognizes the syndrome, which is a crucial step to prevent and cure the predictable malignancy.

Adult↗
PubMed1995

Isotopic response.

BACKGROUND: The occurrence of a new skin disorder exactly at the site of another one, already healed and unrelated, was first described in 1955. In 1985, Wolf et al. recognized that we are dealing with a dermatologic phenomenon and established a precise definition for this phenomenon. Fifty-eight cases corresponding to the definition of this phenomenon have been reported until now. METHODS: The new phenomenon, for which the term "isotopic response" has been suggested, has been defined. Cases corresponding to the definition have been analyzed with special emphasis on the diseases involved, the time intervals, and the locations of the diseases. Eight new cases are described. RESULTS: A total of 58 cases of isotopic response have been described. The first disease in most of the patients was herpes zoster; in three cases it was herpes simplex, in two varicella, and in one, thrombophlebitis. The second disease, which appeared exactly at the site of the first, already healed disease, was in most reported cases a carcinoma (26 cases, in particular 15 cases of breast carcinoma, 5 basal cell carcinomas (BCC), 4 squamous cell carcinomas (SCC), 2 basosquamous carcinomas), or granuloma annulare (16 cases). Additional diseases were Kaposi's sarcoma (2 cases), pseudolymphoma (2 cases), sarcoid (2 cases), tinea (2 cases), tuberculoid and vasculitis granuloma (1 case), angiosarcoma, metastasis, Bowen's disease, lymphoma, leukemia cutis, and acne (1 case each). The diseases did not show any predilection for a particular location. The interval between the first and second disease was extremely variable (ranging from days to years) and showed no particular features. In the eight additional cases described in the present report, the first disease was herpes simplex (6 cases) or herpes zoster (2 cases). The second disease was viral warts (3 cases) or squamous cell carcinoma (2 cases). Additional diseases were furunculosis, contact dermatitis, and molluscum contagiosum (1 case each). CONCLUSIONS: The new term, "isotopic response," describes the occurrence of a new skin disorder at the site of another, unrelated, and already healed skin disease. It is suggested that the term "isotopic response" be included in the lexicon (glossary) of dermatology. Introducing the new term and classifying all the cases under a single key word, will make it possible to locate and collect them easily and to search for the mechanism underlying this phenomenon.

Aged↗
PubMed1995

Pemphigus and dietary factors. In vitro acantholysis by allyl compounds of the genus Allium.

BACKGROUND: Today it is generally accepted that every drug that possesses an active thiol group in its molecule is capable of inducing pemphigus in vivo and provoking acantholysis in vitro. We therefore suggested that plants, in particular those belonging to the Allium group, that contain several active compounds with stable disulfide and thiol groups in their molecule may cause the same. OBJECTIVE: To verify this hypothesis by investigating the in vitro acantholytic effect of three compounds of garlic. METHODS: Skin samples from donors were cultured in the presence of three compounds of garlic (i.e. allylmercaptan, allylmethylsulfide and allylsulfide) for 3 days. The skin samples were then processed for microscopic control for acantholysis. RESULTS: Results indicate that, indeed, the three garlic compounds tested are capable of inducing acantholysis in vitro. Focal and diffuse acantholysis was observed in the specimens from 4 out of 7 donors cultured in the presence of 6 and 9 mM of each of the allyl compounds for 3 days. Interestingly, tissues from a DR4+ donor proved to be more acantholysis prone than others, showing large blistering due to diffuse acantholysis, thus indicating that individual susceptibility plays a crucial role also in vitro. CONCLUSION: Garlic compounds with stable disulfide and thiol groups in their molecule are capable of inducing acantholysis in vitro. These findings lend further support to the theory that 'harmless' nutritional factors are capable of inducing acantholysis in vitro and possibly also in vivo. In view of these findings, it is suggested that nutritional factors should be added to the ever-growing list of exogenous factors capable of inducing pemphigus.

Acantholysis↗
PubMed1993

Imbalance between plasminogen activator and its inhibitors in thiol-induced acantholysis.

Pemphigus may be an idiopathic disease or a syndrome induced by drugs, mainly thiol drugs. Autoantibodies, always present in the idiopathic form but often lacking in the drug-induced one, may cause acantholysis by activating endogenous proteolytic enzymes. Pathogenesis of drug-induced pemphigus when antibodies are absent has not been elucidated yet. Extracts of skin tissues cultured for 4 days with penicillamine, captopril or thiopronine were assayed for the presence of plasminogen activator (PA) and plasminogen activator inhibitors (PAI) on agar fibrin plates. Moreover, uPA, tPA, and PAI-1 were identified in the extracts by immunoenzymatic assay. The results have shown progressively decreasing amounts of PAI-1 in penicillamine, thiopronine and captopril-cultured tissue extracts, respectively. This suggests that the acantholytic potential of thiol drugs is directly correlated to their capability of reducing PAI-1 in the epidermal cells leading to increased PA activity. This PA-PAI imbalance may be itself the cause of intraepidermal splitting.

Acantholysis↗
PubMed1993

Ocular involvement correlated with age in patients affected by major and intermedia beta-thalassemia treated or not with desferrioxamine.

We examined 25 patients affected from Cooley's disease and five by beta-thalassemia intermedia. The mean age was 15 +/- 6.3 years. Fifteen patients, (18 years or older) three of them affected by beta-thalassemia intermedia, presented ocular abnormalities. So it was impossible to establish a correlation between laboratory data and ocular damages; their observation, with reference to untreated beta-thalassemia subjects, suggested that ocular abnormalities cannot be only attributed to desferrioxamine treatment.

Adolescent↗
PubMed1992

Enalapril: a powerful in vitro non-thiol acantholytic agent.

Drugs containing sulfhydryl groups (thiol drugs) (e.g., penicillamine, captopril, thiopronine) can induce pemphigus in vivo and provoke acantholysis in vitro. Enalapril, like captopril, is an angiotensin-converting enzyme (ACE) inhibitor largely used as an antihypertensive drug; it has recently been reported to induce pemphigus, though it is not a thiol drug. In this study we investigated the possible in vitro acantholytic effect of enalapril on normal human skin from donors. The drug induced severe acantholytic changes of keratinocytes and complete suprabasal splitting at one tenth the concentration required by thiol drugs in similar experiments, even after a shorter period of culture. All skin samples from different donors was highly susceptible to the acantholytic effect of enalapril. In our experience, enalapril is the most powerful acantholytic drug in vitro.

Acantholysis↗
PubMed1992

"Two-step" pemphigus induction by ACE-inhibitors.

Pemphigus lesions appeared in a 58-year-old man who was taking captopril for his hypertension. Drug withdrawal resulted in complete remission of the eruption. The subsequent use of enalapril as an antihypertensive agent caused a recurrence of pemphigus lesions along with onset of itching and dermographism. Intercellular antibodies were not found. Discontinuance of enalapril therapy had no effect on the clinical course. Steroid treatment was needed to resolve the eruption. Recently repeated immunofluorescent studies disclosed intercellular IgG antibodies in the serum at a low titer. Pemphigus induction could be initially related to the thiol acantholytic property of captopril. Subsequent production of intercellular antibodies and drug-activation of the kinin system could be responsible for relapsing.

Anti-Inflammatory Agents↗
PubMed1992

Drug-triggered pemphigus in a predisposed woman.

A 31-year-old woman with three pemphigus-prone antigens in her HLA haplotype (B7, DR4, DQw7) developed the disease soon after taking a pyrazolone derivative, viz. feprazone. The pemphigus lesions persisted despite withdrawal of the drug and worsened appreciably when she used ceftriaxone (a new cephalosporin with three sulphur atoms) for a bout of acute pharyngitis. Thiol groups formed from the metabolic breakdown of ceftriaxone are thought to have promoted acantholysis via a biochemical route. Genetic predisposition alone ('the soil') may be essential, though not per se sufficient for outbreak of pemphigus; the intervention of exogenous, heterogeneous factors ('the seed') often seems decisive in triggering full-blown disease.

Adult↗