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Biomedical subjects

R Giacomelli

Publications and source records attributed to R Giacomelli.

49 records · Page 3Linked to original sources
PubMed1989

Evidence of drug interaction between cyclosporin A and H2-receptor antagonists (cimetidine, ranitidine and famotidine) in Sprague-Dawley rats.

H2-receptor antagonists, such as cimetidine (C), ranitidine (R) and famotidine (F) seem to be effective in the prevention and treatment of stress ulcer in transplant recipients receiving cyclosporin A (CyA). The aim of this study was to detect the possible synergistic nephro- and hepato-toxicity of these drugs, assaying the serum creatinine (SC), ALT, AST levels, and the histological features of 45 young male Sprague-Dawley rats, divided into nine groups of five rats each. After 10 days of treatment the results showed: (i) serum CyA levels were increased in the group receiving daily CyA (5 mg/kg) + R(5 mg/kg) (2430 +/- 403 ng/ml; p less than 0.05 vs. controls) and in the group receiving daily CyA (5 mg/kg) +/- C (10 mg/kg) (2440 +/- 265 ng/ml; p less than 0.01 vs. controls); (ii) ALT and AST levels were increased in this latter group (ALT 223 +/- 133 UL, AST 114.67 +/- 39 UL; p less than 0.01 vs. controls); (iii) SC levels were normal; and (iv) steatosis of the liver was observed in these two groups. These findings suggest that C and R, but not F, may inhibit the hepatic cytochromes P-450 which are involved in the oxidative metabolism of the drugs. Furthermore, the high serum CyA levels seem to play a major role in the appearance of biochemical and histological damage to the liver.

Alanine Transaminase↗
PubMed1989

Polyclonal B lymphocyte activation in progressive systemic sclerosis.

In 13 women affected by progressive systemic sclerosis (PSS) the activation state of circulating B lymphocytes by use of monoclonal antibodies and the in vitro IgG, IgA, IgM synthesis by peripheral blood mononuclear cells (PBMC) cultured with or without pokeweed-mitogen (PWM) were evaluated. The total and "activated" B lymphocytes were increased. The supernatants of PBMC cultured without PWM contained increased IgG and IgA levels; only in two patients, however, were IgM levels increased. The addition of PWM augmented IgG and IgA levels only in three cases and never IgM levels. Our results indicate that the polyclonal hyperactivity of B lymphocytes is a major immunologic feature in PSS patients. The lack of increase of in vitro immunoglobulin synthesis in the presence of PWM suggests either that B lymphocytes, already maximally activated in vivo, are unresponsive to further mitogen stimulation or that a more complex imbalance of B lymphocyte responsiveness to PWM may exist.

Adult↗
PubMedDate not supplied

Piascledine modulates the production of VEGF and TIMP-1 and reduces the invasiveness of rheumatoid arthritis synoviocytes.

BACKGROUND: In rheumatoid arthritis (RA), hypertrophy of the synovial membrane generates a tumour-like pannus that invades the joint cavity and erodes cartilage and bone. Invasion of the extracellular matrix (ECM) is accompanied by angiogenesis, in which vascular endothelial growth factor (VEGF) and tissue inhibitors of metalloproteinases (TIMPs), produced by synoviocytes lining the pannus, have a primary role. Piascledine (PSD) is used in the treatment of osteoarthritis and has anti-inflammatory effects in vitro. OBJECTIVE: To study the effects of PSD on levels of VEGF and TIMP-1 and chemoinvasion in RA synoviocytes and healthy controls. METHODS: The effects of PSD 5, 10, and 20 microg/mL were evaluated, with/without interleukin-1beta (IL-1beta) and tumour necrosis factor-alpha (TNFalpha) 20 ng/mL, on synoviocytes. The levels of VEGF and TIMP-1 were assayed in the culture medium by enzyme-linked immunosorbent assay (ELISA). Chemoinvasion was measured by the Boyden chamber invasion assay. RESULTS: RA synoviocytes treated with PSD showed, compared to basal, lower levels of VEGF (41080+/-830 vs. 79210+/-920 pg/106 cells, p<0.001) and increased levels of TIMP-1 (23540+/-93.2 vs. 12860+/-42.9 ng/106 cells, p<0.001). PSD decreased dose-dependently IL-1beta and TNFalpha induced migration. CONCLUSIONS: In RA synoviocytes, and also to a lesser extent in control cells, PSD modulates VEGF and TIMP-1 and decreases chemoinvasion. PSD might have a role in the treatment of RA synovitis controlling invasiveness.

Arthritis, Rheumatoid↗
PubMedDate not supplied

T lymphocytes in the synovial fluid of patients with active rheumatoid arthritis display CD134-OX40 surface antigen.

OBJECTIVE: To assess the percentage of T lymphocytes, bearing CD134, a member of the TNF receptor superfamily, primarily found on autoreactive CD4+ T cells in the peripheral blood (PB) and synovial fluid (SF) of rheumatoid arthritis (RA) patients. METHODS: The surface expression of CD134 on SF and PB mononuclear cells was performed by flow cytometry in 25 RA patients and correlated to the disease activity. RESULTS: CD134 expression on CD3+, CD4+, CD8+ and CD25+ cells was higher in SF than in PB of RA patients (P < 0.001). No differences were observed in the percentage of CD134+/CD4+ T lymphocytes in the PB of RA patients and controls. Patients with active RA had significantly higher percentage of CD3+/CD134+, CD4+/CD 134+, CD8+/CD134+ and CD25+/CD 134+ than those with inactive disease. CONCLUSION: These findings suggest that CD134+ T cells are involved in the immunopathological process of RA synovitis, maybe mirroring some other autoimmune disease in which autoreactive T cell infiltrating the target tissues largely coexpress CD134.

Adolescent↗
PubMedDate not supplied

Combination therapy with cyclosporine and methotrexate in patients with early rheumatoid arthritis soon inhibits TNFalpha production without decreasing TNFalpha mRNA levels. An in vivo and in vitro study.

OBJECTIVE: To evaluate the ability of two different combination therapies with prednisone (PDN), methotrexate (MTX) and cyclosporine (CSA) to modulate both TNFalpha transcription and production in early rheumatoid arthritis (RA). METHODS: 24 patients with early RA received a step-down bridge therapy with MTX and PDN (group A). Twelve patients out of the 24 randomly received also CSA (group B). Blood samples and peripheral blood mononuclear cells (PBMC) were collected at different times. TNFalpha levels were measured both in sera and in PBMC supernatants. TNFalpha mRNA was assessed by use of RT-PCR. RESULTS: 10 patients in group A and 9 in group B improved. At baseline, RA patients serum TNFalpha levels were increased compared to controls (p < 0.001) and did not correlate with clinical and serological parameters. These levels decreased within the first month of therapy in both groups, the lower levels being observed in the sera of CSA treated patients. After 30 days of therapy, TNFalpha levels in group B supernatants were significantly lower than those observed in group A, both after 24 and 48 hours of PHA stimulation (p < 0.03 and p < 0.05 respectively). TNFalpha mRNA levels never differed between patients and controls, independently of both the clinical picture and the assigned therapy. CONCLUSION: The addition of CSA to a treatment regimen of PDN + MTX lowers TNFalpha production in vitro without decreasing TNFalpha mRNA expression. This effect could help to induce early immunosoppressive and therapeutic effects during RA.

Adult↗
PubMedDate not supplied

Gamma/delta T cells in placenta and skin: their different functions may support the paradigm of microchimerism in systemic sclerosis.

Increased amounts of foetal cells persisting after pregnancy could be involved in the pathogenesis of systemic sclerosis (SSc) and other autoimmune diseases. Evidence suggests a specific role for a subset of T lymphocytes showing the gamma/delta T cell receptor (TCR) at the foetal/maternal interface. gamma/delta T cells significantly increase in the early pregnancy decidua and recognize trophoblast antigens, probably a highly evolutionarily conserved molecule such as Hsp60 or Hsp60-derived peptides, and are likely to suppress the maternal anti-foetal immune response via TGFbeta production, thus contributing to pregnancy maintenance. The similarity between the presence of host gamma/delta T cells in pregnancy decidua and in SSc skin suggests that the functional activities of these cells can be differentially modulated by several mechanisms including the nature of the antigen and the involved organs. To support pregnancy, the decidual microenvironment might induce a Th2 activity of host Vdelta1 + T cells. On the contrary, either the presence of foetal cells in the skin of SSc patients or an as yet unidentified stimulus (i.e. infections), may trigger Vdelta1 + T cells toward the Th1 phenotype with the subsequent activation of cytotoxicity and modulation of the cytotoxic alpha/beta acquired T cell response. On these grounds, understanding the mechanisms which prevent the maternal immune system from rejecting a semiallogenic foetus could be helpful to understand the development of some autoimmune diseases, and potentially to develop new targeted therapeutic strategies.

Chimera↗
PubMedDate not supplied

The fibrinolytic system components are increased in systemic sclerosis and modulated by Alprostadil (alpha1 ciclodestryn).

OBJECTIVES: To evaluate urokinase plasminogen activator (u-PA), urokinase plasminogen activator soluble receptor (su-PAR), plasminogen activator inhibitor 1 (PAI-1) and tissue plasminogen activator (t-PA) plasma levels in SSc patients (pts) versus healthy controls and their modulation by intravenous alphacyclodestrine (Alprostadil). METHODS: Plasma levels of u-PA, su-PAR, PAI-1 and t-PA were measured in 40 SSc (34 lSSc and 6 dSSc) pts and in 30 healthy controls. In SSc, blood was drawn before and after 3 consecutive daily of Alprostadil infusion (60 mg in 250 cc NaCl 0.9%). RESULTS: In SSc su-PAR basal levels were higher than controls (7.48 +/- 2.5 vs 4.69 +/- 0.4 ng/ml; p = 0.001) and were significantly reduced by Alprostadil (5.93 +/- 1.7; p = 0.002), but remain higher than controls (p = 0.03). u-PA basal levels were higher than controls (3.78 +/- 1.5 vs 1.29 +/- 0.3 ng/ml; p < 0.001) and were reduced by Alprostadil (2.39 +/- 1.7; p < 0.001) to control levels. SSc PAI-1 basal levels were lower than controls (31.60 +/- 7.7 vs 48.30 +/- 6.8 ng/ml; p < 0.001) and increased by Alprostadil (34.66 +/- 5.4; p = 0.04), but lower than controls (p < 0.001). SSc t-PA basal levels were higher in respect to controls (1645.81 +/- 792.7 vs 571.95 +/- 75.5 pg/ml; p < 0.0001) and reduced by Alprostadil (1318.06 +/- 603.5; p = 0.04), but still higher than controls (p = 0.001). CONCLUSION: Fibrinolysis were increased in SSc. Infusions of Alprostadil modulate u-PA, su-PAR, PAI-1 and t-PA, restoring near normal levels. In SSc, fibrinolysis system may become a potential target for new therapies.

Aged↗
PubMedDate not supplied

[Heterogeneity of epitopes of the CD4 molecule in a female patient with idiopathic pulmonary fibrosis].

Heterogeneity of the CD4 antigen epitopes has been occasionally reported in healthy subjects, in patients affected by autoimmune diseases, such as Graves' disease and systemic lupus erythematosus (SLE), and recently also in HIV-infected subjects. A 63-year-old woman was admitted to the hospital because of dyspnea, autoimmune thrombocytopenia and serum antinuclear autoantibodies. The clinical course and X-ray films of the chest were consistent with idiopathic pulmonary fibrosis. The evaluation of peripheral blood lymphocyte subsets showed low CD4+ cells by use of OKT4 (Ortho Mune) monoclonal antibody (30%, normal range 35-45) and normal values of the same CD4+ subset by use of OKT4A (Ortho Mune) and Leu3a (Becton Dickinson) monoclonal antibodies (48%, normal range 45-55), which are specific for a different epitope of CD4 molecule. These differences indicate that the patient is heterozygous for the OKT4 epitope deficiency on CD4+ lymphocytes surface. The routine use of a panel of monoclonal antibodies, such as OKT4, OKT4A, Leu3a, which recognize different CD4 epitopes, is suggested in order to perform an accurate evaluation of CD4+ lymphocyte subset in patients affected by immune-mediated disorders other than Graves' disease and SLE.

Antibodies, Monoclonal↗
PubMedDate not supplied

The syndrome of idiopathic CD4+ lymphocytopenia.

The syndrome of idiopathic CD4+ lymphocytopenia has recently been recognized and referred to as the persistent depletion of peripheral blood CD4+ T lymphocytes below 300 cells per cubic millimeter or less than 20% of total lymphocytes in the absence of either HIV infection or other known causes of immunodeficiency. The available literature indicates that neither human retroviruses (HIV-1, HIV-2, HTLV-I, HTLV-II) nor other transmissible agents play any clear-cut role in the pathogenesis. Furthermore, the epidemiologic, immunologic and clinical features of this syndrome differ substantially from those of HIV infection. The heterogeneity of both immunologic abnormalities, in addition to CD4+ depletion, and clinical course in patients with this disorder points out no common cause although in at least a subset of patients the pathogenetic pathways could be shared with common variable immunodeficiency.

Humans↗
PubMedDate not supplied

Evaluation of the morphological and functional damage to human sperm subjected to freezing at -196 degrees C and to refrigeration at +4 degrees C.

A study was carried out on five healthy, fertile donors to evaluate refrigeration at +4 C compared to cryopreservation at -196 degrees C. These donors had produced more than two pregnancies in different women with their cryopreserved semen in an AID program. The following parameters for evaluation and comparison were used: (i) the percentage of forward sperm motility, (ii) the percentage of swollen sperm after hypoosmotic stress (swelling test) and (iii) the sperm morphology observed both with a light microscope after staining and with an electron microscope. After 48 hours of refrigeration the result obtained were comparable with those observed after one week of cryopreservation. After 72 hours of refrigeration, a sharp and significant decrease of these values was noted. Our data underlined the fact that there is an individual variability in subject response to the method of preservation employed. Our findings show the possibility of using sperm refrigerated for up to 48 hours in AIH programs.

Analysis of Variance↗