Epidemio-clinical profile of human scabies through dermatologic consultation. Retrospective study of 1148 cases

We report a retrospective study of all scabies cases collected in the department of Dermatology of Charles Nicolle Hospital during a 8 year-period (1993-2000). 148 cases of scabies were collected with a mean incidence of 144 new cases/year (65-204). Diagnosis was made clinically in all cases. Parasitological exam was done in case of doubtful diagnosis. Our purpose is to try to define an epidemio-clinical profile of scabies in Tunisia and to estimate the incidence of this parasitosis through our dermatological consultation with reviewing the literature data.     

Psoriasis: an update

Psoriasis is a frequent dermatosis observed in 2 to 3% of people. It usually begin at the second decade of age but can also affect children. Diagnosis is often easily made by clinical exam. How ether many problems characterise this pathology and are not actually resolved: problems about epidemiology, etiology, treatment and psychological effects.     

MRI findings in pituitary-hypothalamic axis Langerhans cell histiocytosis

Pituitary-hypothalamic axis Langerhans cell histiocytosis is an uncommon entity. It is a rare disease in adults. The CT and MR study provides us the best anatomo-topographic evaluation and determine the precise size of the lesion which are necessary to the treatment. We report a case of hypothalamic involvement by Langerhans cell histiocytosis accompanied by lesions in bone affecting a 31-year-old woman. The clinical, histiotological and CT/MR findings of histiocytosis X are described in this article.     

Feedback inhibition by RALT controls signal output by the ErbB network

The ErbB-2 interacting protein receptor-associated late transducer (RALT) was previously identified as a feedback inhibitor of ErbB-2 mitogenic signals. We now report that RALT binds to ligand-activated epidermal growth factor receptor (EGFR), ErbB-4 and ErbB-2.ErbB-3 dimers. When ectopically expressed in 32D cells reconstituted with the above ErbB receptor tyrosine kinases (RTKs) RALT behaved as a pan-ErbB inhibitor. Importantly, when tested in either cell proliferation assays or biochemical experiments measuring activation of ERK and AKT, RALT affected the signalling activity of distinct ErbB dimers with different relative potencies. RALT deltaEBR, a mutant unable to bind to ErbB RTKs, did not inhibit ErbB-dependent activation of ERK and AKT, consistent with RALT exerting its suppressive activity towards these pathways at a receptor-proximal level. Remarkably, RALT deltaEBR retained the ability to suppress largely the proliferative activity of ErbB-2.ErbB-3 dimers over a wide range of ligand concentrations, indicating that RALT can intercept ErbB-2.ErbB-3 mitogenic signals also at a receptor-distal level. A suppressive function of RALT deltaEBR towards the mitogenic activity of EGFR and ErbB-4 was detected at low levels of receptor occupancy, but was completely overcome by saturating concentrations of ligand. We propose that quantitative and qualitative aspects of RALT signalling concur in defining identity, strength and duration of signals generated by the ErbB network.     

Treatment of colon and breast carcinoma cells with 5-fluorouracil enhances expression of carcinoembryonic antigen and susceptibility to HLA-A(*)02.01 restricted,CEA-peptide-specific cytotoxic T cells in vitro

Cancer vaccines directed against tumor associate antigen (TAA) have produced encouraging results in preclinical models but not in cancer patients. A major limitation of this strategy is the relative degree of tolerance to these antigens and the low and heterogeneous tumor cell expression of TAA and major histocompatibility complex (MHC). Previous studies have shown that 5-fluorouracil (5-FU) can upregulate the expression of membrane-associated carcino-embryonic antigen (CEA), and MHC molecules in colon and breast carcinoma cell lines. We have investigated whether this drug can also enhance their sensitivity to the lytic effects of CEA-peptide specific Cytotoxic T cell lymphocytes (CTL). The CEA peptide-specific CTLs generated in our laboratory from normal HLA-A(*)02.01(+) donor PBMCs, were able to kill HLA-A(*)02.01(+)/CEA(+) breast (MCF-7-T103) and colon (HLA-A(*)02.01 gene-transfected HT-29 and C22.20) carcinoma cells in HLA-A(*)02.01 restricted manner. The treatment of target cells with 5-FU, enhanced their CEA expression and susceptibility to CTL-mediated lysis. Cold competition assays confirmed these results, thus supporting the hypothesis that immune target cell lysis and 5-FU mediated enhancement were dependent on CEA peptide presentation by cancer cells. 5-FU treatment of functionally "mature" CTL after in vitro expansion, did not reduce their cytolytic activity against MT-2 target cells but, when the anti-metabolite was added during the immune-sensitization phase, CTL generation was significantly inhibited. These results provide a rationale for investigating a possible new role of 5-FU as an immuno targeting amplifier agent in breast and colorectal cancer patients immunized with CEA-directed cancer vaccines.     

Induction of metallothionein is correlated with resistance to auranofin, a gold compound, in Chinese hamster ovary cells

Metallothioneins (MTs) are low molecular weight, thiol-rich, metal-binding proteins. Auranofin (AF) is a gold compound active in the treatment of rheumatoid arthritis. The effects of AF on regulation of MT gene expression in Chinese hamster ovary cells were studied. AF-resistant cells accumulated substantial amounts of MT mRNA and protein, whereas no induction was observed in AF-sensitive cells. Cells capable of inducing MT in the presence of AF were much less sensitive to AF-mediated cytotoxicity. Induction of MT by low concentrations of Cd protected cells from subsequently administered doses of AF. The level of protection correlated with the level of induced MT. These findings indicate that MT plays a central role in the mechanisms underlying cellular resistance to gold compounds.     

Epidemiological and clinical features of giant cell arteritis in Tunisia

BackgroundGiant cell arteritis (GCA) is a systemic vasculitis of the elderly that could result in vision loss or even be life threatening. Unlike western countries, this disease is considered exceptional in Tunisia.ObjectiveThe aims of this study were to determine epidemiological and clinical features of GCA in Tunisian population and to identify management difficulties.Patients and methodsA multicentric study of 96 patients in whom GCA was diagnosed between 1986 and 2003. All patients fulfilled the ACR criteria for classification of GCA.ResultsThe majority of cases (77%) were diagnosed since 1994. The male/female ratio was 0.88 and the mean age at the time of diagnosis was 70.8 ± 7.7 years. Clinical features were characterized by gradual onset in 64.4% of cases. The most frequent clinical manifestations were headache (91.7%), abnormalities in temporal arteries (85.4%), severe ischemic manifestations (80.2%), constitutional symptoms (75%), and polymyalgia rheumatica (56.3%). Biological inflammatory syndrome was noted in all patients. Temporal artery biopsy established histological diagnosis in 73% of cases. All patients were treated by corticosteroids. Remission was obtained in 45.6%. Relapses occurred in 40.4% of cases and 30 patients were still receiving corticosteroids at the time of study. Four patients died and irreversible ischemic complications were noted in 15.6% of cases. Steroid adverse effects occurred in 56 patients.ConclusionGCA is not exceptional to Tunisia. It occurs amongst elderly patients with no female predominance noticed. Clinical features are similar to those reported in other series.     

Inhibition of Bcl-xL expression sensitizes normal human keratinocytes and epithelial cells to apoptotic stimuli.

The epidermis is continually exposed to harmful mutagens that have the potential to cause DNA damage. To protect the skin from accumulating mutated cells, keratinocytes have developed a highly regulated mechanism of eliminating damaged cells through apoptosis. Bcl-xL is a well-described cell survival protein that when overexpressed in skin can protect keratinocytes from UV radiation-induced apoptosis. To begin to unravel the complex mechanisms that keratinocytes use to survive, we wanted to characterize the role of endogenous Bcl-xL in protecting cells from death. In this study, we describe the development and characterization of an antisense inhibitor to Bcl-xL. We show that this inhibitor reduces Bcl-xL RNA and protein in a concentration-dependent, sequence-specific manner. Furthermore, treatment of keratinocytes and epithelial cells with this inhibitor sensitizes these cells to UV-B radiation and cisplatinum treatment-induced apoptosis. Thus, these results offer direct evidence that Bcl-xL is critical in the protection of skin and epithelial cells from apoptosis and provide a basis for the role of Bcl-xL in keratinocyte and epithelial cell survival.     

In vitro activities of voriconazole in combination with three other antifungal agents against Candida glabrata

Candida glabrata has recently emerged as a significant pathogen involved in both superficial and deep-seated infections. In the present study, a checkerboard broth microdilution method was performed to investigate the in vitro activities of voriconazole (VOR) in combination with terbinafine (TRB), amphotericin B (AMB), and flucytosine (5FC) against 20 clinical isolates of C. glabrata. Synergy, defined as a fractional inhibitory concentration (FIC) index of < or = 0.50, was observed in 75% of VOR-TRB, 10% of VOR-AMB, and 5% of VOR-5FC interactions. None of these combinations yielded antagonistic interactions (FIC index > 4). When synergy was not achieved, there was still a decrease in the MIC of one or both drugs used in the combination. In particular, the MICs were reduced to < or = 1.0 microg/ml as a result of the combination for all isolates for which the AMB MIC at the baseline was > or = 2.0 microg/ml. By a disk diffusion assay, the halo diameters produced by antifungal agents in combination were greater that those produced by each drug alone. Finally, killing curves showed that VOR-AMB exhibited synergistic interactions, while VOR-5FC sustained fungicidal activities against C. glabrata. These studies demonstrate that the in vitro activity of VOR against this important yeast pathogen can be enhanced upon combination with other drugs that have different modes of action or that target a different step in the ergosterol pathway. Further studies are warranted to elucidate the potential beneficial effects of such combination regimens in vivo.