In vitro effect of antigenic extract of trichophyton verrucosum on fibroblast proliferation and matrix metalloproteinase -2 activities

Trichophyton verrucosum is a zoophilic fungus with a worldwide distribution. Our aim was to investigate the proliferative effect of antigenic compounds of T. verrucosum on dermis fibro blasts and endothelial cells. T. verrucosum was cultured in SCC medium and was then transferred to a broth medium. Surface antigens of this fungus were separated using the freeze and thaw method. The sample was centrifuged and the supernatant was taken. The supernatant was homogenized and purified. The prepared antigenic extract was added to fibro blast cell lines according to a regular timetable. Cytotoxicity and cell proliferation were evaluated using zymography and densitometry in order to assay MMPs activity. Statistical analyses showed that this antigenic extract is able to enhance the MMPs activity. Trichophyton verrucosum increases the proliferation of dermis germinal layer and MMP-2 activity, which has a direct relation with wound healing process

effects of arsenic trioxide and zoledronic acid on malignant plasma cells derived from bone marrow cells of multiple myeloma patients

Multiple myeloma [MM] is a disease of plasma cells that has fatal consequences. New agents associated with molecular targets have prompted clinical investigators to design new treatment strategies initially for advanced MM and later for newly diagnosed MM, with encouraging preliminary results. We devised a project to assess the mechanisms of action of two drugs, Arsenic trioxide [ATO] and Zoledronic acid [Zometa] on Bone marrow mononuclear cells [BMMCs] derived from patients. Bone marrow samples were collected from 10 patients after receipt of formal consent. BMMCs were collected from samples. In two parallel sets of experiments, BMMCs were treated with 0.5, 2, 6 micro M ATO and 0.1, 10, 100 micro M Zometa, for 72 h. The following analyses were then performed on treated cells as compared to untreated cells [assumed as control]: cytotoxicity using Micro culture tetrazolium test [MTT assay]; matrix metalloproteinase-2 zymography; comparative gene expression analysis of IL-6, vascular endothelial growth factor [VEGF] and intercellular adhesion molecule-1 [ICAM-l]. MTT assay showed significant proliferation inhibition in ATO high dose treatment [6 uM]. However, no significant inhibitory effect of Zometa was seen. Zymography analyses showed significant decrease in gelatinolytic activity in treated cells. Analyses of gene expression using Real-Time RT-PCR methodology showed significant decrease in IL-6, ICAM-1, and VEGF genes as normalized against Hypoxanthine phosphoribosyltransferase normalizer and as compared with untreated cells. Both ATO and Zometa could significantly decrease MM cells critical phenotype and genotype. This finding could support the hypothesis that ATO or Zometa could inhibit growth and metastasis of malignant cells

Thl/Th2 cytokines in psoriasis

The aim of this study was to determine the Thl and Th2 serum cytokines, in patients with psoriasis and to compare their cytokine levels with those of normal control subjects. Serum levels of Interferon-gamma [IFN-gamma], Interleukin-2 [IL-2], Interleukin-4 [IL-4], and Interleukin-10 [IL-10] were measured by enzyme linked immunosorbent assay in 40 patients with psoriasis and in 40 normal controls. Compared with control subjects, patients with psoriasis had elevated levels of IFN-gamma and IL-2 [P<0.001]. In addition a positive correlation was found between the levels of IFN-gamma, IL-2 and disease severity. Thl secreting inflammatory cytokines may contribute to the pathogenesis of psoriasis

Arsenic trioxide compound modulates multiple myeloma phenotypes: Assessment on cell line models

Recent evidences suggest that multiple myeloma phenotypes [MMPs] are involved in the infiltration of multiple myeloma-affected marrow foci. In this study, the effects of arsenic trioxide on the invasive and angiogenic phenotypes of multiple myeloma [MM] cell line were assessed on a dose-response and time-course basis. Multiple myeloma cell line, Karpas 707, was treated with step-wise elevated concentrations of arsenic trioxide compound at 24, 48, and 72 h intervals. Cytotoxicity was assessed with a colorimetric assay. Potential antiinvasive phenotype was analyzed with MMP-2 zymography. To verify directly the anti angiogenic effect, F1 endothelial cell line was also treated with arsenic and the dose-dependent cytotoxicity was assessed with a colorimetric assay. Apoptotic properties of arsenic trioxide compound were investigated using TUNEL assay. The significant dose-dependent inhibitory effects of arsenic trioxide on MMP-2 were seen at given concentrations. Cytotoxicity analysis revealed much higher cell death than untreated cells [P< 0.01], both in Karpas 707 and F1 endothelial cell lines. Colectively, this study showed that arsenic trioxide might potentially elicit anti-invasive anti-angiogenesis properties in the treatment of myeloma dissemination process. In addition, the concurrent inhibition of MMPs activity and endothelial cell proliferation could compose the scenario of neoangiogenesis inhibition in the marrow-infiltrated foci

Effect of tindurin on immunopathogenesis mechanism of collagen-induced arthritis

Rheumatoid arthritis is a chronic inflammatory disease characterized by the sequestration of various leukocyte subpopulations within both the developing pannus and synovial space. This study was undertaken to examine the therapeutic potency of tindurin in experimental rheumatoid arthritis. Collagen-induced arthritis [CIA] was induced by intradermally immunization of Lewis rats at the base of the tail. The paws and knees were then removed for histopathology and radiography analysis. Using fibrosarcoma cell line the apoptosis process was measured by Terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labeling [TUNEL] method. Our data showed that the i.p. injection of tindurin to arthritic rats induced a significant reduction in paw edema. Histopathological assessment showed reduced inflammatory cells infiltrate, tissue edema and bone erosion in joints of treated rats. Moreover, our results in radiography were in line with histological findings as well as tindurin was found to induce apoptosis of treated cells in comparison with positive, negative and non-treated ones. Our findings revealed the therapeutic effect of tindurin in experimental model of rheumatoid arthritis in comparison with methotrexate as a choice drug