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Biomedical subjects

Eleonora Ruocco

Publications and source records attributed to Eleonora Ruocco.

At least 19 recordsLinked to original sources

Quinine sulfate inhibits invasion of some bacterial skin pathogens.

BACKGROUND: As some of the many patients who receive antimalarials for the treatment of noninfective inflammatory diseases (lupus erythematosus, collagen vascular diseases, rheumatoid arthritis, and others) are also immunosuppressed because of their disease and/or treatments, and may have concomitant bacterial infections, we investigated the effect of these drugs on the growth and invasion of several bacteria that are commonly associated with skin and soft tissue infections to determine whether they could protect against such conditions and obviate the need for an additional antibiotic drug. METHODS: The effect of quinine sulfate (QS) at concentrations of 50 and 100 microm on the entry process of Enterobacter agglomerans, Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumoniae into Caco-2 cells was studied during the infection period. The invasive efficiency was expressed as the number of viable internalized bacteria obtained by counting the colony-forming units (CFUs). RESULTS: The invasive ability of E. agglomerans and S. aureus was significantly inhibited by 50 and 100 microm QS in a dose-dependent manner when the drug was added to Caco-2 cell monolayers during the infection period; however, QS had no significant effect on the internalization of P. aeruginosa or K. pneumoniae. DISCUSSION AND CONCLUSIONS: Antimalarial drugs are currently widely used to treat patients with autoimmune dermatologic and rheumatologic diseases, and have also been recently proposed as additional therapy for patients with human immunodeficiency virus (HIV) infection. These patients, who are often immunocompromised, may receive a secondary advantage from these antimalarials, which may provide some protection against staphylococci (amongst the most important human pathogens causing many superficial and systemic infections) and E. agglomerans.

Adenocarcinoma↗

The putative role of apoptosis in the induction of pemphigus.

The apoptotic cell has recently been shown to play a central role in tolerizing B cells and T cells to both tissue-specific and ubiquitously expressed self-antigens, and to possibly drive the autoimmune response in systemic lupus erythematosus, an autoimmune disease which bears many similarities to pemphigus. We now propose a similar mechanism in the induction of pemphigus, namely, that a dysregulation in apoptosis expressed as an impairment of normal programmed cell death of epidermal keratinocytes and/or deficient and inadequate clearance of apoptotic material (specifically, desmoglein) may render it antigenic with the consequent production of autoantibodies. The fact that some thiol-containing compounds which are well-known inducers of acantholysis in vitro and pemphigus in vivo were shown to inhibit apoptosis might support our hypothesis.

Apoptosis↗

Vascular structures in skin tumors: a dermoscopy study.

OBJECTIVES: To describe the different vascular structures seen by dermoscopy and to evaluate their association with various melanocytic and nonmelanocytic skin tumors in a large series of cases. DESIGN: Digital dermoscopic images of the lesions were evaluated for the presence of various morphologic types of vessels. SETTING: Specialized university clinic. PATIENTS: From a larger database, 531 excised lesions (from 517 patients) dermoscopically showing any type of vascular structures were included. MAIN OUTCOME MEASURES: The frequency and positive predictive value of the different vascular structures seen in various tumors were calculated, and the differences were evaluated by the chi2 or Fisher exact test. RESULTS: Arborizing vessels were seen in 82.1% of basal cell carcinomas, with a 94.1% positive predictive value (P<.001). Dotted vessels were generally predictive for a melanocytic lesion (90.0%, P<.001), and were especially seen in Spitz nevi (77.8% of lesions). In melanoma, linear-irregular, dotted, and polymorphous/atypical vessels were the most frequent vascular structures, whereas milky-red globules/areas were the most predictive ones (77.8%, P = .003). The presence of erythema was most predictive for Clark nevus, whereas comma, glomerular, crown, and hairpin vessels were significantly associated with dermal/congenital nevi, Bowen disease, sebaceous hyperplasia, and seborrheic keratosis, respectively (P<.001 for all). CONCLUSIONS: Different morphologic types of vessels are associated with different melanocytic or nonmelanocytic skin tumors. Therefore, the recognition of distinctive vascular structures may be helpful for diagnostic purposes, especially when the classic pigmented dermoscopic structures are lacking.

Adult↗

Possible role of Malassezia furfur in psoriasis: modulation of TGF-beta1, integrin, and HSP70 expression in human keratinocytes and in the skin of psoriasis-affected patients.

BACKGROUND: Psoriasis is a disease characterized by an abnormal pattern of keratinocyte growth and differentiation. Malassezia furfur forms part of the normal human skin flora. It may also be involved in the pathogenesis of psoriasis. To define the role of M. furfur in the pathogenesis of psoriasis, we investigated how M. furfur regulates molecules involved in cell migration and proliferation. The experiments were performed using human keratinocytes and skin biopsies from M. furfur-positive and -negative psoriasis-affected patients. In addition, we examined the signal transduction mechanisms involved. MATERIALS AND METHODS: Western blot analysis was performed on human keratinocytes lysates treated or untreated with M. furfur and on biopsies from healthy and psoriasis patients. Signal transduction mechanisms involved were evaluated by electrophoretic mobility shift assay using the AP-1 inhibitor curcumin. RESULTS: We found that M. furfur up-regulates transforming growth factor-beta1 (TGF-beta1), integrin chain, and HSP70 expression in human keratinocytes via AP-1-dependent mechanism. In the biopsies of M. furfur-positive psoriasis-affected patients, an increase in TGF-beta1, integrin chains, and HSP70 expression was found. CONCLUSION: Our data suggest that M. furfur can induce the overproduction of molecules involved in cell migration and hyperproliferation, thereby favoring the exacerbation of psoriasis.

Blotting, Western↗

Noninvasive imaging of skin tumors.

In this article, the authors review different approaches to the diagnosis of skin tumors using noninvasive diagnostic tools, which are becoming increasingly reliable and, as a consequence, increasingly popular among physicians and patients. Especially in the realm of pigmented skin lesions, dermoscopy and sonography may add useful information to the clinical constellation, improving the diagnostic performance for early diagnosis of melanoma and for differentiating various melanocytic and nonmelanocytic pigmented lesions. More recently, confocal scanning laser microscopy was introduced as a novel technique that enables the in vivo study of the skin at a nearly histologic resolution, being of diagnostic value in various skin disorders, including basal cell carcinoma and pigmented skin lesions. These modalities have various other potential applications besides diagnosis, including lesion's selection for biopsy, determination of appropriate therapeutic modalities, verification of treatment efficacy, and decision of surgical margins. Finally, a hint to the use of cytodiagnosis for basal cell carcinoma is provided.

Basal Cell Carcinoma↗

Three-point checklist of dermoscopy. A new screening method for early detection of melanoma.

BACKGROUND: Dermoscopy used by experts has been demonstrated to improve the diagnostic accuracy for melanoma. However, little is known about the diagnostic validity of dermoscopy when used by nonexperts. OBJECTIVE: To evaluate the diagnostic performance of nonexperts using a new 3-point checklist based on a simplified dermoscopic pattern analysis. METHODS: Clinical and dermoscopic images of 231 clinically equivocal and histopathologically proven pigmented skin lesions were examined by 6 nonexperts and 1 expert in dermoscopy. For each lesion the nonexperts assessed 3 dermoscopic criteria (asymmetry, atypical network and blue-white structures) constituting the 3-point method. In addition, all examiners made an overall diagnosis by using standard pattern analysis of dermoscopy. RESULTS: Asymmetry, atypical network and blue-white structures were shown to be reproducible dermoscopic criteria, with a kappa value ranging from 0.52 to 0.55. When making the overall diagnosis, the expert had 89.6% sensitivity for malignant lesions (tested on 68 melanomas and 9 pigmented basal cell carcinomas), compared to 69.7% sensitivity achieved by the nonexperts. Remarkably, the sensitivity of the nonexperts using the 3-point checklist reached 96.3%. The specificity of the expert using overall diagnosis was 94.2% compared to 82.8 and 32.8% achieved by the nonexperts using overall diagnosis and 3-point checklist, respectively. CONCLUSION: The 3-point checklist is a valid and reproducible dermoscopic algorithm with high sensitivity for the diagnosis of melanoma in the hands of non-experts. Thus it may be applied as a screening procedure for the early detection of melanoma.

Adult↗

Quinine sulfate and HSV replication.

Although antimalarial drugs have been developed primarily to treat malaria, they are also beneficial for many dermatological, immunological, and rheumatological diseases, for which they are mostly used today in the Western world. The aim of the present study was to investigate the effect of quinine sulfate (QS) on the multiplication and adsorption of herpes virus type I (HSV-1). When Vero cells (African green monkey kidney) are infected with HSV-1 in the presence of QS, the viral adsorption is reduced, as demonstrated by a decrease of the number of microscopic plaques of the virus. When the virus-infected Vero cells are incubated in the presence of QS, the multiplication of HSV-1 is also reduced, and the diameter of the plaque are visibly smaller. The practical implications of the antiviral action of antimalarial drugs might be especially important to immunosuppressed patients who receive these drugs for autoimmune collagen-vascular diseases or as additional therapy for AIDS.

Animals↗

Quinine sulfate and bacterial invasion.

BACKGROUND: As many patients who receive antimalarial drugs for treatment of noninfectious, inflammatory diseases are also immunosuppressed and might have a concomitant bacterial infection, we studied the effectiveness of these drugs against bacterial infections, to find out whether they could protect against (and even treat) such conditions and obviate the need for an additional antibiotic drug. METHODS: Effect of QS on bacterial growth: Escherichia coli (E. coli) HB101 pRI203 were cultured overnight at 37 degrees C in TSB and inoculated (approx 1 x 10(7) cells/ml) in MEM in the presence of QS at various concentrations (0, 50 and 100 microM).The effect of QS at concentration of 50 and 100 microM on the entry process of E. coli HB101 pRI203 into HeLa cells was studied under different experimental conditions: 1. QS was incubated with 3 x 10(5) HeLa cells for 60 min at 37 degrees C prior to infection. 2. QS was added to HeLa cell monolayers during the infection period. RESULTS: QS showed no antibacterial activity after 24 h of incubation. The invasive efficiency of the bacteria was significantly inhibited at a dose-dependent manner, when QS was added to HeLa cells for 60 min at 37 degrees C prior to infection (condition 1), and to a lesser extent when added during the period of infection (condition 2). CONCLUSIONS: Although the antimalarials are generally regarded as being inactive against most extracellular bacterial species, our results indicate that QS significantly inhibited the internalization/invasion efficacy of E. coli in the host cells.

Journal Article↗

Corticosteroid-sparing effect of intravenous immunoglobulin therapy in patients with pemphigus vulgaris.

BACKGROUND: Pemphigus vulgaris (PV) is a rare, potentially fatal autoimmune mucocutaneous blistering disease. The prolonged use of systemic corticosteroids, though clinically effective in high doses, can result in multiple debilitating adverse effects. Immunosuppressive agents, used as adjuvants and as corticosteroid-sparing agents, are not effective in all patients and are contraindicated in some. Therefore, alternative treatment modalities are needed to provide effective control of PV in such patients. OBJECTIVE: To demonstrate the corticosteroid-sparing effect of intravenous immunoglobulin (IVIg) therapy in patients with moderate to severe PV. DESIGN: A retrospective analysis in a cohort of 15 patients with moderate to severe PV who were treated with IVIg therapy. All 15 patients were corticosteroid dependent, and the use of other systemic conventional immunosuppressive agents was contraindicated. The patients were followed up over a mean period of 6.2 years. SETTING: Ambulatory tertiary medical care facility of a university-affiliated hospital. INTERVENTION: All 15 patients received an IVIg dose of 1 to 2 mg/kg per cycle. MAIN OUTCOME MEASURES: The following information was documented in each of the 15 patients before and after the initiation of IVIg therapy: total dosage and total duration of prednisone therapy and number of relapses. Also, the highest dosage and adverse effects of prednisone therapy, as well as the total duration of observation, were recorded. RESULTS: All 15 patients had a satisfactory clinical response to IVIg therapy. The use of systemic prednisone was gradually discontinued over a mean period of 4.3 months. A statistically significant difference was noted in the total dose of prednisone (P =.004), total duration of prednisone therapy (P =.003), and number of relapses (P<.001) before and after the initiation of IVIg therapy. CONCLUSIONS: Intravenous immunoglobulin therapy has a demonstrable corticosteroid-sparing effect. It is a safe and effective alternative treatment modality in patients with PV who are dependent on systemic corticosteroids or who develop significant adverse effects as a result of their use.

Adult↗

Isotopic response after herpesvirus infection: an update.

The term postherpetic isotopic response describes the occurrence of a new, unrelated disease that appears at the same location as a previously healed herpetic infection. When dealing with the pathogenetic mechanism involved in the isotopic response, several possibilities should be considered: a viral origin, an immunologic origin, a vascular origin, and a neural origin. The aim of this article is to review and discuss the different pathogenetic mechanisms with particular attention to new information related to the possible neural origin of this abnormal response of the skin.

Herpesviridae Infections↗

Lymphedema: an immunologically vulnerable site for development of neoplasms.

Lymphedema is the result of accumulation of protein-rich interstitial fluid (lymph stasis) caused by a failure of lymph drainage in the face of a normal capillary filtration. Whether the origin is congenital or acquired from infection, radiation, trauma, or surgery, chronic lymph stasis impairs local immune surveillance by disrupting trafficking of the immunocompetent cells in the lymphedematous district and stimulates vicarious angiogenesis by promoting development of a collateral lymphatic and hematic network in the lymphedematous district. When the local mechanisms of immune surveillance begin to fail, the lymphedematous region becomes an immunologically vulnerable area, predisposed to malignancy, chiefly vascular tumors such as Stewart-Treves syndrome and Kaposi's sarcoma, because of the continual angiogenic stimulus.

Female↗

Cytokine pattern in blister fluid and sera of patients with pemphigus.

BACKGROUND: Pemphigus is a chronic auto-immune blistering disease with four main variants, i.e. pemphigus vulgaris (PV), foliaceus (PF), erythematosus (PE) and vegetans. The common histological feature of this disease is acantholysis. OBJECTIVE: The aim of this study was to compare levels of some cytokines in blister fluid and sera of patients with pemphigus, using as control blister fluid of patients with bullous pemphigoid (BP) and bullous contact dermatitis (BCD). METHODS: Using an immuno-enzymatic assay (ELISA), we tested 16 sera and 6 blister fluids of patients with various forms of pemphigus (13 with PV, 1 with PF, 2 with PE), the sera of 16 healthy control subjects, 5 blister fluids of patients with BP and 5 blister fluids of patients with BCD, for the presence of some cytokines (IL-10, IL-8 and IFN-gamma). Intercellular antibodies were searched for and titred; desmoglein 1 and 3 antibody levels were independently evaluated to compare them with the severity of both cutaneous and oral involvement. RESULTS: The levels of IL-10 in the sera of patients with pemphigus were below the detection limits. IL-8 was significantly increased only in 4 samples of sera from pemphigus patients compared with controls, while IFN-gamma was detected at low levels in almost all patients compared with sera of controls. The cytokine levels in blister fluid of patients with pemphigus were significantly higher than in the sera. There was a difference between the expression of cytokines in blister fluid of control patients with BP and BCD compared with those of pemphigus patients. CONCLUSION: This report discusses the anti-inflammatory role played by IL-10 in the chronic form of pemphigus and the hypothesis of a possible role of IL-8 in neutrophil and lymphocyte-monocyte recruitment.

Adolescent↗

Life-threatening bullous dermatoses: Pemphigus vulgaris.

Pemphigus vulgaris (PV) is a rare autoimmune bullous dermatosis with a high mortality rate if untreated. The disease results from autoimmunity to normal components of keratinocyte cell membrane (desmogleins 3 and 1) belonging to the cadherin supergene family. Standard therapy for PV is based on a combined administration of high-dosed glucocorticoids and immunosuppressive drugs. In patients with severe, life-threatening, or recalcitrant PV, stronger therapeutic options should be considered, such as 'pulse-therapy' with discontinuous intravenous infusion of megadoses of immunosuppressive drugs over a short-time, plasmapheresis, and extracorporeal immunoadsorption of pathogenic autoantibodies using the extracellular domain of the PV main antigen (desmoglein 3) produced by baculovirus or, more recently, a tryptophan-linked polyvinyl alcohol adsorber.

Autoimmune Diseases↗