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Vered Molina

Publications and source records attributed to Vered Molina.

8 recordsLinked to original sources
PubMed2006

Immunomodulation of experimental pulmonary fibrosis by intravenous immunoglobulin (IVIG).

OBJECTIVES: To assess the immunomodulatory effect of intravenous immunoglobulin (IVIG) using an experimental model of bleomycin-induced pulmonary fibrosis. METHODS: Pulmonary fibrosis was induced in C57BL/6 mice by direct intratracheal injection of bleomycin. Mice were treated with IVIG 1 week prior to (prevention protocol), or 10 days following bleomycin injection, when the disease was in progress. The controls used in the study included mice given phosphate buffered saline (PBS) and mice subjected to a commercial individual-IgG. Collagen-I deposits in the affected lungs were detected by Sirius red staining of paraffin embedded lung sections. The collagen-I content was measured by employing the hydroxyproline assay. RESULTS: Prevention of bleomycin-induced pulmonary fibrosis by IVIG has been demonstrated by reduced expression of collagen-I protein in the affected lungs. The hydroxyproline levels in the lungs of the IVIG-treated mice were 214.33 +/- 13.56 microg/1 g tissue, compared to the higher levels in lungs of IgG treated mice (342.44 +/- 35.60 microg/1 g tissue) or untreated controls 328.00 +/- 45.55 microg/1 g tissue, (p < 0.0001). Effective treatment of bleomycin-induced pulmonary fibrosis by IVIG has been demonstrated by the reduced expression of collagen-I protein in the affected lungs, detected by sirius red histological staining. The hydroxyproline levels in the lungs of the IVIG-treated mice were 261.00 +/- 18.81 microg/1 g tissue, in comparison to the higher levels in the lungs of the IgG treated mice (342.43 +/- 32.89 microg/1 g tissue) and of untreated controls (344.33 +/- 49.85 microg/1 g tissue), (p < 0.001). CONCLUSIONS: Based on these preliminary studies, we conclude that IVIG may have a beneficial effect in the down regulation of collagen-I levels in the lungs of mice with bleomycin-induced pulmonary fibrosis.

Animals↗
PubMed2005

Infection, vaccines and other environmental triggers of autoimmunity.

The etiology of autoimmune diseases is still not clear but genetic, immunological, hormonal and environmental factors are considered to be important triggers. Most often autoimmunity is not followed by clinical symptoms unless an additional event such as an environmental factor favors an overt expression. Many environmental factors are known to affect the immune system and may play a role as triggers of the autoimmune mosaic.Infections: bacterial, viral and parasitic infections are known to induce and exacerbate autoimmune diseases, mainly by the mechanism of molecular mimicry. This was studied for some syndromes as for the association between SLE and EBV infection, pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection and more. Vaccines, in several reports were found to be temporally followed by a new onset of autoimmune diseases. The same mechanisms that act in infectious invasion of the host, apply equally to the host response to vaccination. It has been accepted for diphtheria and tetanus toxoid, polio and measles vaccines and GBS. Also this theory has been accepted for MMR vaccination and development of autoimmune thrombocytopenia, MS has been associated with HBV vaccination. Occupational and other chemical exposures are considered as triggers for autoimmunity. A debate still exists about the role of silicone implants in induction of scleroderma like disease.Not only foreign chemicals and agents have been associated with induction of autoimmunity, but also an intrinsic hormonal exposure, such as estrogens. This might explain the sexual dimorphism in autoimmunity.Better understanding of these environmental risk factors will likely lead to explanation of the mechanisms of onset and progression of autoimmune diseases and may lead to effective preventive involvement in specific high-risk groups. So by diagnosing a new patient with autoimmune disease a wide anamnesis work should be done.

Animals↗
PubMed2005

Intravenous immunoglobulin and fibrosis.

Fibrosis is a pathological process that includes scar formation and overproduction of extracellular matrix by the connective tissue as a response to tissue damage. Pathologies include pathological scarring as colloid and hypertrophic scars in the skin, cirrhosis of liver and gallbladder, pulmonary and bone-marrow fibrosis, and scleroderma. The molecular process is not different from normal formation of connective tissue and extracellular matrix in the normal organs. Major profibrotic agents are type 2 CD4-positive lymphocytes, CD40 receptor and ligand interaction, and the cytokines interleukin-4, transforming growth factor-beta, and platelet-derived growth factor. The major antifibrotic agent is interferon-gamma. Fibrosis was considered an irreversible process, at least clinically, and is still usually treated by anti-inflammatory and immunosuppressive agents. No proven antifibrotic therapy has shown efficacy in ameliorating clinical fibrosis. Intravenous immunoglobulin has a very good safety profile, and was found to be an ameliorating agent for several fibrotic diseases, and hence could be a drug of choice to these patients and improve their quality of life.

Animals↗
PubMed2003

Inhibition of ras by farnesylthiosalicylate significantly reduces the levels of autoantibodies in two animal models of the antiphospholipid syndrome.

BACKGROUND: Stimulation and proliferation of lymphocytes require activation of Ras. S-farnesylthiosalicylic acid (FTS) is a synthetic substance that detaches Ras from the inner cell membrane and induces its rapid degradation. Antiphospholipid antibodies (aPL) are a heterogeneous group of antibodies detected in patients with antiphospholipid syndrome (APS), which is associated with thrombosis, pregnancy losses, and thrombocytopenia. OBJECTIVE: To examine the effect of FTS treatment on aPL levels in a genetic autoimmune model (the MRL/lpr mice) and in an induced model of APS. METHODS: Female Balb/C mice immunized once with beta2-glycoprotein I (beta2-GPI) in complete Freund's adjuvant (CFA) and female MRL/lpr mice were treated intraperitoneally with either FTS (5 mg/Kg/day) or saline 3-5 times a week. aPL and anti-beta2-GPI antibodies were measured by ELISA. RESULTS: FTS treatment 3 times a week resulted in significant decreases of aPL and anti-beta2-GPI antibodies in both animal models. In contrast, more frequent treatment (5 times a week) had no significant effect on autantibody levels in both animal models. We further compared 2 protocols in the induced APS model, one for alternate day treatment and the other for daily treatment on the first 3 days each week, and found a decrease in autoantibody levels only in the alternate day protocol. CONCLUSIONS: Inhibition of Ras activation by FTS is effective in decreasing autoantibody levels in models of APS. The differential modulation of immune function by alternate day compared to daily treatment may provide better understanding of the role of Ras activation in this system.

Animals↗
PubMed2002

[Fibrotic diseases].

Fibrosis is a pathologic process, which includes scar formation and over production of extracellular matrix, by the connective tissue, as a response to tissue damage. The molecular process is not different from normal formation of connective tissue and extracellular matrix in the normal organs. The context, the environment and the over production make the difference. Fibrosis formation includes interaction between many cell types and cytokines, and when the balance becomes profibrotic, there is fibrosis formation. Major profibrotic agents are type 2 CD4 positive lymphocytes, CD40 receptor and ligand interaction, and the following cytokines: IL-4, transforming growth factor b, platelet derived growth factor. The major antifibrotic agent is interferon gamma. Pathologies include: in the skin pathologic scarring as colloid and hypertrophic scar, cirrhosis of liver and gallbladder, in the heart and the kidneys, pulmonary and bone-marrow fibrosis, and scleroderma. Scleroderma is chronic connective tissue disease, expressed clinically by systemic sclerosis and diffuses fibrosis of the skin and viscera. This is a progressive degenerative disorder of the blood vessels, skin, lungs, kidneys, heart and GI tract and for this reason this disease plays a major role in fibrosis research. Fibrosis is considered an irreversible process, at least clinically, and is usually treated by anti-inflammatory and immunosuppressive agents. This kind of therapy was not proven successful and sometimes it harms more than cures. Many patients suffer from fibrotic diseases and the aim is to develop anti-fibrotic agents, targeted to the pathologic molecular process. Progressing step by step in this issue has direct clinic affect.

Cytokines↗
PubMedDate not supplied

Autoantibodies and prediction of reproductive failure.

PROBLEM: To determine which autoantibodies are associated with reproductive failure. METHOD OF STUDY: Sera from 269 patients with autoimmune disease and/or reproductive failure were analyzed for anti-phospholipid (aPL), anti-annexin-V, anti-lactoferrin, anti-thyroglobulin, anti-thyroid peroxidase, anti-prothrombin, anti-nuclear, and anti-saccharomycetes cerevisiae antibodies (ASCA), by enzyme-linked immunosorbent assay. Patients were classified as: recurrent pregnancy loss (RPL), infertility, and autoimmune diseases. The results were compared with those of 120 healthy volunteers. RESULTS: In autoimmune diseases, the prevalence of anti-prothrombin, anti-annexin, anti-phospholipid and anti-nuclear antibodies was significantly higher than in the control group, OR 11.0 [CI, 3.5-35.2], 33 [CI, 7.2-174.2], 13 [CI, 1.4-309.7], and 16.1 [CI 2.4-122], respectively. In infertility, the antibodies with significantly higher levels than controls were: aPL OR, 5.11 [CI 1.2-25.4], and anti-prothrombin antibodies, OR, 5.15 [CI, 2.1-12.7]. In RPL, ASCA, anti-prothrombin and aPL were more prevalent than in controls, OR 3.9 [CI, 1.5-10.6], 5.4 [CI, 2.4-12.5] and 4.8[CI, 1.2-22.2] for each antibody, respectively. Anti-prothrombin antibodies and aPL were more significantly associated with late pregnancy losses than early losses. CONCLUSION: ASCA antibodies have not previously been described in RPL. Nor are anti-prothrombin antibodies usually assessed in infertility or RPL. If these results are confirmed in further studies, these antibodies might be assessed routinely in reproductive failure.

Abortion, Spontaneous↗