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Biomedical subjects

E Ruocco

Publications and source records attributed to E Ruocco.

At least 19 recordsLinked to original sources
PubMed2005

Immunomodulatory effects of a set of amygdalin analogues on human keratinocyte cells.

Peptide T (PT) is an octapeptide shown to resolve psoriatic lesions. Our previous investigations suggest that keratinocytes play an important role in conditioning the therapeutic effects of the PT in psoriasis. However, peptides are not good therapeutic agents, because they exhibit poor absorption, are easily metabolized and are immunogenic. Using computational methods, the natural product amygdalin was identified as peptidomimetic of PT. However, amygdalin exhibits a toxic profile due to its cyanide group. To overcome this deleterious effect, we synthesized analogues lacking the cyanide group. Human keratinocytes were treated with PT or with three different peptidomimetics of PT. To study its effects on the expression of HSP-70, TGF-beta, alpha-v integrin, ICAM-1 and cytokines, we analysed the protein levels by Western blot and ELISA. Our results show that the different peptidomimetics of PT tested exhibit a similar biological behaviour in regard to the overexpression of HSP-70, TGF-beta and alpha-v integrin than the native peptide. TNF-alpha is overexpressed by PT and SVT-03018; between the other two analogs, SVT-03016 do not produce any significant change in regard to the control, while SVT-03017 shows only a moderate increase in regard to control. SVT-03018 provokes a remarkable upregulation of IL-10, stronger than SVT-03016, SVT-03017 and PT. All the other three analogues reduce comparably to the PT, the expression of ICAM-1 and do not increase the release of proinflammatory cytokines. The results highlighted that the three analogues of amygdalin with the cyanide group removed exhibit the same biological effects of PT. Therefore, they can be considered peptidomimetics, suggesting their possible use in the treatment of psoriasis.

Amygdalin↗
PubMed2004

Pemphigus serum and captopril induce heat shock protein 70 and inducible nitric oxide synthase overexpression, triggering apoptosis in human keratinocytes.

BACKGROUND: Captopril is an angiotensin-converting enzyme inhibitor with sulphydryl groups in its chemical structure. It is commonly used as an antihypertensive drug. The occurrence of pemphigus vulgaris has repeatedly been reported in patients receiving captopril. The capacity of captopril and pemphigus serum to induce acantholysis, in vivo or in vitro, has been demonstrated experimentally. OBJECTIVES: To show that captopril and pemphigus serum, acting by a biochemical and immunological mechanism, respectively, trigger apoptosis. METHODS: Human keratinocyte cells were treated with 15 mmol L-1 captopril or with pemphigus serum. DNA was extracted and the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling method was used to detect apoptosis. RESULTS: DNA fragmentation occurred after 72 h of treatment. Increased expression of p53, c-myc and inducible nitric oxide (NO) synthase (iNOS) mRNA were observed by polymerase chain reaction (PCR) in the treated cells compared with the untreated ones. The increase in iNOS gene expression was associated with overproduction of NO. Moreover, the addition of 1 mmol L-1N-monomethyl-L-arginine, a structural analogue of arginine, reduced nitrite levels by about 70% in cells treated with captopril or pemphigus serum. Western blot analysis revealed an overexpression of heat shock protein 70 (hsp70) in cells treated with captopril or pemphigus serum. Finally, total inhibition of the keratinocyte transglutaminase gene was shown by PCR analysis in the same samples, compared with control cells. CONCLUSIONS: These data demonstrate the involvement of apoptosis in keratinocytes treated with captopril or pemphigus serum, with induction of the iNOS gene and hsp70 in the cascade of events leading to programmed cell death.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2003

Kaposi's sarcoma: aetiopathogenesis, histology and clinical features.

UNLABELLED: Kaposi's sarcoma (KS) represents today one of the most common skin cancers in transplanted Mediterranean subjects and, since the epidemic of human immunodeficiency virus/acquired immune deficiency syndrome, in young unmarried single men. The disease has been associated with the recent identified human herpesvirus (HHV)-8 or KS herpesvirus and its incidence in the general population shows a north to south gradient that parallels the HHV-8 increasing prevalence from Nordic countries to sub-Saharan regions. The identification of the aetiopathogenetic mechanisms (viral agents and immunodeficiency) involved in the pathogenesis of KS, are relevant for identifying susceptible subjects (HHV-8 seropositive subjects), monitoring the immune levels in iatrogenic immune suppressed patients, and developing new therapeutic approaches based on antiviral and immune modulators. LEARNING OBJECTIVE: This article should enable the reader: (i) to learn about the clinical and molecular aspects of KS in order to have a multidisciplinary approach to a tumour that shows unique features; (ii) to consider the role of viral agents and immunity; and (iii) to recognize properties of an opportunistic neoplasm. The identification of the HHV-8 role in KS pathogenesis should establish a relevant tool in the clinical management of KS patients.

AIDS-Related Opportunistic Infections↗
PubMed2003

Granuloma annulare in a site of healed herpes zoster: Wolf's isotopic response.

A case of granuloma annulare that developed in a site of healed herpes zoster is reported. Polymerase chain reaction failed to detect VZV DNA in a biopsy specimen. The occurrence of different types of cutaneous reactions in a body area previously affected by herpes virus infection is known as Wolf's isotopic response. Pathogenesis may be due to a local neuroimmune dysregulation set off by herpesvirus-induced lesions of dermal sensory nerve fibres.

Antiviral Agents↗
PubMed2001

Uptake of Malassezia furfur by human dermal fibroblasts: effect of ketoconazole and cytoskeleton inhibitors.

We showed the ability of human dermal fibroblasts to take up Malassezia furfur and the effect of ketoconazole and cytoskeleton inhibitors, including cytochalasin D and colchicine, on invasivity. Engulfment was evaluated by May Grunwald Giemsa stain and confirmed by acridine orange staining and electron microscopy. Both revealed the different steps of engulfment, including a fusion event between lysosomes and phagosomes containing M. furfur. Subinhibitory concentrations of ketoconazole (5 microg/ml) reduced the invasive capacity compared to controls (52.0+/-6.3 vs 10.0+/-1.2). M. furfur induced changes in the cytoskeleton of human dermal fibroblasts, with signs of disaggregation of actin fibres. We also studied the effect of the cytoskeleton inhibitors, cytochalasin D (1 microg/ml) and colchicine (1 microg/ml), on engulfment. Cytochalasin D, an inhibitor of actin polymers, inhibited the uptake of M. furfur by human dermal fibroblasts. Colchicine, a microtubule inhibitor, reduced the uptake of M. furfur less markedly. This suggests that the process of engulfment is F-actin-dependent, but the integrity of microtubules is also important in "non-professional" phagocytic cells such as dermal fibroblasts.

Antifungal Agents↗
PubMed2001

Malassezia furfur invasiveness in a keratinocyte cell line (HaCat): effects on cytoskeleton and on adhesion molecule and cytokine expression.

The lipophilic yeast Malassezia furfur is a member of the cutaneous microbiota, also associated with several chronic diseases such as pityriasis versicolor, folliculitis, seborrhoeic dermatitis, and some forms of atopic dermatitis, psoriasis and confluent and reticulate papillomatosis. In this study we determined the immunomodulatory and invasive capacity of M. furfur in a human keratinocyte cell culture, HaCat. At a yeast cell to HaCat ratio of 30:1, M. furfur penetration was only 30% with poor phagolysosome fusion and with cytoskeleton modification. Transglutaminase I gene expression was also inhibited, supporting the hypothesis that M. furfur causes an initial break in the barrier function of the epidermis. Moreover, we demonstrated that M. furfur modulates proinflammatory and immunomodulatory cytokine synthesis by downregulating IL-1alpha and by inhibiting IL-6 and TNF-alpha and by upregulating IL-10 and TGF-beta1. The suppressed inflammatory response induced by M. furfur may play a role in chronic disease.

Cell Division↗
PubMed2001

A possible role of catenin dyslocalization in pemphigus vulgaris pathogenesis.

BACKGROUND: Pemphigus vulgaris (PV) is an autoimmune blistering disease of the skin and mucosa due to the presence of autoantibodies against the components of desmosomes. To date, less is known about the expression levels of beta- and gamma-catenins in blistering diseases. The objective of this study was to evaluate the role of beta- and gamma-catenins in the pathogenesis of acantholysis in pemphigus vulgaris. METHODS: beta- and gamma-catenin expression was evaluated by immunohistochemistry in 30 cases of PV at various stages of the disease and, as controls, in 18 specimens of the skin/oral mucosa of healthy patients. RESULTS: Healthy skin and normal oral mucosa showed a strong beta- and gamma-catenin expression in basal and spinous layers with a prevalent cellular membrane distribution; the intensity of staining progressively decreased toward the superficial layers of epithelium. In PV patients, cytoplasmic expression of gamma-catenin was detected in 28/30 cases, and in 19/30 cases of PV for beta-catenin. Moreover, a progressive displacement of the signal toward the nucleus was found in 14/30 cases for beta-catenin, with dyslocalization toward the nucleus, particularly in areas with intense acantholysis, and in 22/30 cases of PV for gamma-catenin. CONCLUSIONS: Abnormal distribution of gamma-catenin, consequent to PV IgG, may be considered a direct consequence of Dg3 dissociation from catenin. gamma-catenin likely plays a direct role in PV pathogenesis through its dyslocalization toward the nucleus or indirectly through the beta-catenin dyslocalization toward the nucleus, which is thought to induce transcription of selected target genes, such as uPAR.

Acantholysis↗
PubMed2001

Pemphigus vulgaris: environmental factors. Occupational, behavioral, medical, and qualitative food frequency questionnaire.

BACKGROUND: There have been reports suggesting the involvement of environmental factors in the disease process of pemphigus. Factors suggested include exposure to pesticides or certain drugs. OBJECTIVE: To analyze the association of pemphigus with environmental exposure to various agents, including smoking, recreational and occupational insults, drugs, and food. DESIGN AND SETTING: In-person interviews of pemphigus patients and control subjects were conducted by trained medical investigators using a structured questionnaire. Questions included occupational, behavioral, medical, and qualitative food frequency details. The multicenter study was conducted at outpatient services of teaching hospitals in Bulgaria, Brazil, India, Israel, Italy, Spain, and the USA. PARTICIPANTS: A total of 126 pemphigus patients (55 men, 71 women; age, 54 +/- 17 years) and 173 healthy controls (87 men, 86 women; age 50 +/- 19 years) were interviewed in the period between October 1, 1999 and March 31, 2000. The diagnosis of pemphigus was based on clinical, histologic, immunohistologic, and immunohistochemical criteria. The disease duration was 2-27 years (8.4 +/- 7.2 years). Individuals with skin diseases other than pemphigus were selected as control subjects. MAIN OUTCOME MEASURE: Information on drugs, foods, and occupational, environmental, constitutional, and other possible risk factors was analyzed by t-tests and chi-squared tests as applicable. A multivariate logistic regression model was applied to the data to study simultaneously the independent relationship between each risk factor and pemphigus vulgaris. RESULTS: The risk for pemphigus vulgaris was lower for ex-smokers and current smokers than for patients who had never smoked. Exposure to pesticides and occupational exposure to metal vapor were associated with an increased risk of pemphigus. Pemphigus patients had more pregnancies than controls. There were differences in environmental factors between countries, with exposure to gardening materials and pesticides being highest among patients from Bulgaria, followed by Israel. Disease characteristics also exhibited differences between countries. Bulgarian patients less frequently had oral mucous membrane lesions: 66% compared to 92% for Israeli patients and 83% for Italians. The distribution of the disease in skin and mucous membranes was similar among patients from all countries. Exclusive skin involvement was seen in 50% of patients, mucous membranes alone in 23% of patients, and both skin and mucous membranes in 27% of patients. CONCLUSIONS: The beneficial effect of smoking on pemphigus might be explained by its effect on the immune system. In addition, smoking has an antiestrogenic effect, while pesticides have an estrogenic effect. The lower numbers of smokers among patients, the higher exposure rates to pesticides, and the higher number of female patients who had been pregnant may point to the contribution of estrogens to the disease process. It remains to be determined whether measures, such as avoiding exposure to pesticides or metal vapor, may be beneficial in the clinical context. As the present study was a survey, more definitive studies should be conducted to validate the results.

Agriculture↗
PubMed2001

Precautions and suggestions for pemphigus patients.

The onset and course of pemphigus are often the result of an interaction between predisposing genetic factors and environmental triggering agents. The latter are heterogeneous, numerous and increasing, ranging from drug intake (the commonest cause of pemphigus induction) to the exposure to physical agents (heat, UV and ionizing rays, surgical and cosmetic procedures), viral infections (especially by herpesvirus), contact dermatitis, certain diet ingredients and even emotional stress. Alerting physicians and pemphigus patients to the effects that unsuspected precipitating factors may have on the progression of the disease is an important task. In fact, avoiding or limiting deleterious habits (e.g. overindulging in unnecessary drugs) and suggesting alternative ways (e.g. substituting potentially pemphigus-inducing drugs with others considered harmless in this respect) may be a useful precaution in the management of pemphigus patients, since it can improve the efficacy of conventional treatments, reduce the risks of relapses and sometimes result in a cure.

Environmental Exposure↗
PubMed2000

In vitro tannin acantholysis.

BACKGROUND: Exogenous factors, such as certain drugs, may be involved in the induction of pemphigus. Other offenders sharing a similar chemical composition to these drugs may also play a role. Tannins with their considerable biologic activity were suggested as possible factors. To substantiate the role of tannins in the pathomechanism of pemphigus, the present study examined the acantholytic potential of tannins in vitro. METHODS: Normal human breast skin from patients without any bullous disease was cultured for 3 days in the presence of tannic acid at concentrations of 0.02, 0.05, 0.1, 0.25, 0.5, 1.0, and 2.0 mM. The effect of the tannic acid was microscopically examined in a blind fashion by three independent investigators. RESULTS: In addition to the cytotoxic effect, tannic acid caused marked acantholytic changes, with a clear suprabasal cleavage and intraepidermal acantholytic cells. The acantholytic changes were the most constant and specific effects. They were constantly observed at 1.0 and 2.0 mM, whereas lower concentrations showed changes only in some of the explants. The concentrations needed to exert this effect were notably low. There was a remarkable variability among the subjects who had provided the explants. CONCLUSIONS: The results suggest a possible role of tannin in the disease process of pemphigus. The tannin acantholytic potential was much greater than the potential of known acantholytic drugs, such as penicillamine and captopril. The interindividual variability in susceptibility to acantholysis may explain the variability in the individual potential for developing pemphigus.

Acantholysis↗
PubMed2000

Effects of lithium carbonate (Li2CO3) on in-vitro-cultured normal human skin explants.

The early morphological changes induced by lithium carbonate, a well-known psoriasis-provoking drug, were studied on cultured skin. Normal human skin from patients undergoing mastectomy was cultured in the presence of 3 mM, 6 mM and 10 mM of Li2CO3 for 4 days. The morphological changes were then evaluated by three observers in a blind manner and their reports were matched and collated. The cultured skin in the presence of Li2CO3 showed cell crowding of keratinocytes in the lower part of the epidermis, indicating epidermal hyperplasia. Another striking finding was intercellular oedema and vacuolar alteration with formation of small cavities in the upper dermis. There was no evidence of parakeratosis or any other histological characteristic of psoriasis, except hyperproliferation of the epidermis. Based on our knowledge of mechanisms of lithium action, we proposed two competitive explanations for its action on the epidermis: i) that lithium acts directly on dividing cells of the epidermis; and ii) that it acts indirectly by altering epidermal barrier function. Although we lack definite proof, we suggest that the observed morphological changes, in particular the non-specific stimulus to epidermal proliferation, are the primary events which initiate the process that will ultimately lead to the development of psoriasis in a predisposed patient.

Cells, Cultured↗
PubMed1999

Prevalence of left ventricular diastolic filling abnormalities in adult cardiac surgical patients: an intraoperative echocardiographic study.

The incidence of left ventricular (LV) diastolic abnormalities in adult cardiac surgical patients has not previously been adequately investigated. The present study was performed to characterize LV diastolic filling patterns by performing transesophageal Doppler echocardiographic (TEE) studies in patients undergoing cardiac surgical procedures and thus indirectly assess diastolic function in these patients. Doppler TEE studies were performed and transmitral flow (TMF) and pulmonary venous flow (PVF) velocities were recorded in 104 patients intraoperatively. Peak early (E) and late (A) TMF velocities and systolic (S) and diastolic (D) forward PVF velocities were assessed and deceleration time (DT) was measured in all patients. For analysis, the study patients were classified into three groups according to the ratio of the TMF E to A velocity curves: group I with E/A ratio less than 1.0, group II with E/A ratio of 1.0 to less than 2.0, and group III with E/A ratio of 2.0 or greater. A filling pattern of abnormal LV relaxation was found in 73 patients (E/A < 1.0), a normal or pseudonormal pattern was present in 27 patients (1.0 < or = E/A < or = 2.0), and restrictive filling in 4 patients (E/A > 2.0). Patients with impaired relaxation had a greater incidence of recent myocardial infarction and congestive heart failure (CHF) than those with normal or pseudonormal filling patterns. Within group II, patients with CHF had higher TMF E deceleration rates and lower PVF S/D ratios compared with those without CHF (P < .05). Doppler echocardiographic examination of TMF and PVF velocities suggests that abnormalities in diastolic function are prevalent in adult cardiac surgical patients.

Aged↗
PubMed1999

Detection of herpesvirus DNA in peripheral blood mononuclear cells and skin lesions of patients with pemphigus by polymerase chain reaction.

Pemphigus is an autoimmune disease where both endogenous (genetic) and exogenous (environmental) factors play a part. Viral infections, in particular herpesvirus infections, have been identified as a possible triggering factor for pemphigus. In this study, using the polymerase chain reaction, we studied peripheral blood mononuclear cells (PBMC) and skin biopsies from patients with pemphigus, and in some of these were able to demonstrate the presence of DNA sequences of herpes simplex virus 1/2 (50% in PBMC and 71% in skin biopsies), Epstein-Barr virus (15% in PBMC and 5% in skin biopsies) and human herpesvirus 6 (20% in PBMC only). However, the inability to detect herpesvirus DNA consistently in these cases suggests that viral infection may only be an occasional factor triggering the outbreak or exacerbation of the disease. The possible role of interferons and interleukins in the pathogenesis of virus-induced pemphigus is discussed.

Adult↗