Oral ulcerations are frequent lesions resulting from numerous different causes. A precise anamnesis is mandatory to direct towards the diagnosis. It includes the type of the earliest lesion (blister/vesicle or ulceration), the number of lesions (isolated or numerous), the complaints (painful or asymptomatic), the disease evolution (acute, chronic, recurrent), the duration of the ulceration (a few hours, days, weeks, months, years...), the presence of adenopathies and/or the association with clinical lesions on other mucous membranes, on skin, on nails or on scalp. A traumatism or a drug reaction are the first aetiologies to be excluded. Chronic enteropathies or lupus erythematosus or other systemic diseases, especially those leading to immunosuppression, can be responsible for oral ulcerations. These diseases must be diagnosed and treated to obtain an improvement of the oral lesions. Laboratory studies such as microbiological isolation, serology or biopsy, are performed in accordance with the suspected diagnosis resulting from anamnesis and physical examination. Aphthous stomatitis and oral herpes infection present similar features such as symptomatology, recurrences, trigger factors, etc. Differential diagnosis is mandatory to treat correctly the disease. It is easier if the primary lesion (vesicle or ulceration) is observed or if herpes simplex virus is yielded. Oral blisters are uncommon; they especially concern erythema multiforme and bullous auto-immune diseases. A single ulceration directs towards a diagnosis of cancer or chancre. Lichen planus is a frequent disease of the oral mucous membrane with numerous clinical features: erosive and ulcerated lesions are often observed. In all cases, a symptomatic treatment is necessary against pain to permit nutrition, hydratation and good speech. An etiologic treatment is associated as soon as possible.

Oral allergies represent a pathological entity not well known nor diagnosed by dental health professionals. The purpose of this work is to present an information relative to the multidisciplinary steps to be done to solve allergy problems. Three clinical examples of contact oral allergies (to mercury, or gold, or methacrylates) are presented, as to illustrate signs and symptoms of an oral allergy to the more frequent dental materials implied.We discuss the problem of oral allergies from what is known from the scientific literature. We stress the importance of a multidisciplinary approach to take into account patients with an oral allergy, with participation of specialists from dental and dermatologic fields.

Oral allergies are underdiagnosed by dental health professionals. Patients with an oral allergy complain of various symptoms such as burning or tingling sensations, with or without oral dryness or loss of taste, or of more general symptoms such as headache, dyspepsia, asthenia, arthralgia, myalgia. The signs of oral allergy include erythema, labial oedema or purpuric patches on the palate, oral ulcers, gingivitis, geographical tongue, angular cheilitis, perioral eczematous eruption, or lichenoid reactions localized on the oral mucosa. There is an increase in the prevalence of oral allergies to metals used in dental materials. Allergy to gold included in dental prosthesis has been well documented since the years eighties. Recently, titanium, used in orthopedic devices and oral implants, considered as an inert material, can induce toxicity or allergic type I or IV reactions. These reactions to titanium could be responsible for unexplained successive failure cases of dental implants in some patients (named "cluster patients"). The risk of an allergy to titanium is increased in patients who are allergic to other metals. In these patients, an evaluation of allergy is recommended, in order to exclude any problem with titanium medical devices. We stress the importance of a multidisciplinary approach to take into account patients with an oral allergy, with participation of specialists from dental and dermatologic fields.

The purpose of this work was to approach the development of a safe and validable process to grow the amounts of adult Mesenchymal Stem Cells (MSC) necessary for future biomedical applications. Using a single use Vue Life bag system integrated in a simple agitations bioreactor we constructed, we have studied the adhesion, migration and growth properties of MSC on different carriers (Cytodex and Bionoc) in comparison to other cells (endothelial/Kaposi sarcoma cells, CHO and HeLa) in relation to the expression of endogenous Metal loprotemases.

The department of dermatology has developed a broad clinical activity with a particular expertise in oncology, allergology, psoriasis and gynecological dermatology. Research has also been developed in these areas.

Iron is suspected to be involved in the induction and/or progression of various human tumors. The present study was designed to investigate the effects of iron on endothelial cells, keeping in mind that the homeostasis of microvessels plays a critical role in neo-angiogenesis. Applying a model of human dermal microvascular endothelial cell terminal differentiation and death induced by serum deprivation, we found that iron salts (iron chloride and ferric nitrilotriacetate) provided a survival advantage to endothelial cells. Using immunohistochemistry and Western Blot analysis, we found that the extended cellular life span induced by iron was paralleled by an increase of Bcl-2 protein expression. Taken together, these observations suggest that iron may give a survival advantage to endothelial cells and represent a novel mechanism through which iron may contribute to tumorigenesis.

Genital condylomata acuminata are nonmalignant human papillomavirus (HPV)-induced tumors in which HPV types 6 and 11 are most commonly found. Usual treatments for condylomata acuminata are nonspecific and are based on the destruction or removal of infected tissue. These procedures are often painful and are characterized by a high relapse rate. We report here what is to our knowledge the first double-blind, placebo-controlled study of the use of cidofovir, a nucleotide analogue, for the treatment of genital papillomavirus infections. Thirty patients were enrolled in the study; 19 received cidofovir, and 11 received placebo. The median number of warts and the median baseline wart area were comparable for both groups. Nine (47%) of 19 patients in the cidofovir group had a complete response (total healing), compared with 0 of the patients in the placebo group (P=.006). None of the patients in the cidofovir group experienced progression of the disease, compared with 5 (45%) of 11 patients in the placebo group. The side effects recorded for both groups were comparable.

Whether Kaposi's sarcoma is a true neoplasm or a reactive endothelial cell outgrowth triggered by inflammatory cytokines remains unclear. In this study, we investigated the differential invasive properties of activated endothelial cells and Kaposi's sarcoma cells in a model of de-epidermized dermis, supplying the cells with matrix barriers similar to those found in vivo. Cells derived from early "patch-stage" and from late "nodular-stage" Kaposi's sarcoma lesions exhibited similar invasive properties, which indicates that cells with an invasive potential are present in the early stages of tumor development. Slow accumulation of the cells into the extracellular matrix, together with a low proliferation index and with expression of anti-apoptotic proteins, suggest that the progression of Kaposi's sarcoma may be related to escape from cell death rather than to increased proliferation. The Kaposi's sarcoma-Y1 cell line, which is tumorigenic in nude mice, also exhibited invasive properties. By contrast to the Kaposi's sarcoma-derived spindle cells, however, which were scattered between the collagen bundles, the Kaposi's sarcoma-Y1 cell population had a higher proliferation index and displayed a multilayer arrangement. Inflammatory cytokines and Kaposi's sarcoma cell supernatant could activate and stimulate the growth of human dermal microvascular endothelial cell, but could not induce their invasion in this model, showing that activated endothelial cells do not fit all the requirements to traverse the various barriers found in the dermal extracellular matrix. These results confer to Kaposi's sarcoma cells a tumor phenotype and suggest that the in vivo dominant endothelial cell population represents a reactive hyperplasia rather than the true tumor process.

Iron is involved in several biological reactions and is essential to almost all forms of life. In contrast, iron is potentially toxic. It may participate in many dermatological disorders, including pigmentation changes, inflammation, porphyrias, infections and cancers. The involvement of iron in these disorders entails a variety of mechanisms, including among others simple deposition processes, activation or inactivation of enzymatic systems, impairment of phagocyte functions and interference with apoptosis. A better understanding of the role of iron might provide novel therapeutic strategies based on iron-chelating and/or anti-oxidant agents.

The involvement of a viral agent in the pathogenesis of Kaposi's sarcoma (KS) points to antiviral agents as possible therapeutic and/or prophylactic options in the management of the disease. In the present study we investigated the antiproliferative effects of various chemotherapeutic agents, including acyclic nucleoside phosphonates, on the growth of KS-derived cells. Nested PCR amplification demonstrated that these cells do not contain human herpesvirus 8 (HHV-8) DNA sequences. The cytotoxicity of the chemotherapeutic compounds was less pronounced in KS cells than in human dermal microvascular endothelial cells, which are considered to be the normal counterpart of KS cells. Stimulation of KS cells with basic fibroblast growth factor (bFGF) and correction of the IC50 values by the doubling times revealed that the apparent chemotherapeutic resistance of KS cells could mainly be attributed to the long doubling times of these cells. bFGF-stimulated KS cells still exhibited no particular sensitivity to the acyclic nucleoside phosphonates whose activity extends to HHV-8, which is consistent with the absence of linear HHV-8 DNA synthesis in these cells. Our data suggest that neither anti-cancer agents nor antiviral agents such as the acyclic nucleoside phosphonates can discriminate efficiently between KS cells and normal endothelial cells.

We report on a lymphoedematous form of classic Kaposi's sarcoma (KS) in which characteristic purplish lesions were surrounded by atypical oedematous, flesh-coloured papules. Histological examination of these papular lesions revealed a proliferation of grouped, rather thick-walled capillaries with inflammatory infiltrates. Hot-start PCR amplification with KS 330-233 primer sequences demonstrated the presence of human herpesvirus 8 (HHV-8) sequences. In addition, cells isolated from these oedematous papules showed morphological and immunohistochemical features similar to those reported for KS-derived spindle cells. As a whole, these results suggest that these oedematous papular lesions represent pre-KS lesions and may expand the clinico-pathological spectrum of KS. The role of oedema in their induction is discussed.

The effect of intralesional injections of cidofovir, a nucleotide analog with potent in vitro activity against human herpesvirus 8 (HHV-8), was studied in vivo in an HIV-negative patient with classical Kaposi's sarcoma (KS). After five weekly injections of the drug, no clinical, histological, immunohistological, or virological changes could be detected in comparison with saline-injected lesions. These findings suggest that, once the KS tumor has developed, active viral replication is no longer involved in the pathogenesis of the disease. Alternative hypotheses are that HHV-8 replication in blood-borne cells may foster growth of spindle cells in the skin, or that blocking HHV-8 may not affect existing lesions but may prevent new lesions from developing.

The pathogenesis of Kaposi's sarcoma (KS), a tumor of probable vascular origin, remains an enigma, It is still unclear whether KS is a true malignancy or whether it represents a reactive polyclonal process. Using both an immunohistochemical and an immunoblot approach, we found that cells derived from KS lesions express significant levels of Bcl-2, a protein known to prolong cellular viability and to antagonize apoptosis, Bcl-2 expression was found in AIDS-related KS-derived cells, as well as in cells derived from iatrogenic and sporadic KS, indicating that Bcl-2 upregulation may be important in the pathogenesis of KS regardless of its epidemiologic form, By contrast, fibroblasts and dermal microvascular endothelial, cells which are the probable vascular progenitors of KS cells, expressed low levels of Bcl-2, The expression of Bcl-2 in KS-derived cells was associated with a longterm survival in serum-deprived conditions, a situation that has been shown to induce apoptosis in various cell types. Incubation of fibroblasts or of dermal microvascular endothelial cells with KS cell-free supernatants did not enhance Bcl-2 expression, suggesting that Bcl-2 expression is not mediated by an agent released by KS cells, Analogously, KS supernatants failed to promote the viability of fibroblasts and of dermal microvascular endothelial cells cultured in serum-free conditions. Our findings suggest that the spindle cells derived from KS have a survival advantage and may adequately represent the tumor cells of KS.

The role of iron in the pathogenesis of several tumours is being increasingly investigated. In particular, its involvement in the pathogenesis of Kaposi's sarcoma (KS) is suggested by the distribution of the endemic form of KS corresponding to continental rifts and associated iron-oxide-rich volcanic clays. We investigated in vitro to what extent iron supplementation or withdrawal could affect the growth of KS-derived cells, by analysing the effects of adding iron salts (iron chloride and ferric nitrilotriacetate) and/or reducing iron by iron chelators (desferrioxamine) on KS-derived cell cultures. The addition of iron salts strongly stimulated the growth of KS cells, as reflected by increase in thymidine incorporation and cell number. Conversely, desferrioxamine and deferiprone inhibited cell growth. The inhibitory effect of iron chelation was more pronounced on rapidly dividing basic fibroblast-growth-factor-stimulated cells. These results may point to a novel therapeutic approach to KS.

Endothelial cells play a crucial role in a number of pathological conditions and in their regulation. Angiogenesis mechanisms are particularly relevant to the understanding of these different situations (1–2). Cytokines play also an important role in the regulation of pathophysiological responses of endothelial cells and in their overall behaviour.

We report two cases of labial swelling (oral and vulvar) with a granulomatous histology in patients with a history of Crohn’s disease. The differential diagnosis of granulomatous vulvitis and cheilitis, as well as the symptomatology and treatment of vulvar and oral Crohn’s disease are further discussed. To our knowledge, reported cases of vulvar and oral Crohn’s disease are quite scarce in the literature, but the disease might be underdiagnosed. We hope to contribute to an earlier recognition and a better management of the vulvar and oral mucocutaneous lesions of Crohn’s disease.