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Biomedical subjects

M Cutolo

Publications and source records attributed to M Cutolo.

At least 163 records · Page 9Linked to original sources
PubMedDate not supplied

Presence of estrogen receptors in human myeloid monocytic cells (THP-1 cell line).

OBJECTIVE: To test THP-1 cells for the presence of estrogen receptors (ER) since studies have demonstrated in vivo and in vitro, the influence of estrogens on cells involved in immune response (i.e. macrophages), and since it has been demonstrated that human myeloid monocytic THP-1 cells acquire phenotypic and functional macrophage-like features after incubation with several cytokines or pharmacological agents. DESIGN: Stimulation of THP-1 cells with phorbol myristate acetate (PMA) to prompt their differentiation into macrophage-like cells and evaluation of the possible induction of ER. METHODS: The expression of ER was analyzed by immunocytochemical assay, reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot analysis. RESULTS: After stimulation by PMA, the human myeloid monocytic THP-1 cells showed the presence of ER, together with markers of monocytic cell differentiation such as CD68, CD54 and HLA-DR. CONCLUSION: Estrogen effects may be exerted directly through ER on monocytes/macrophages. PMA-treated THP-1 cells may constitute a useful in vitro model to determine the effects of estrogens on macrophage-like cells and their implications in the inflammatory and immune processes.

Antigens, Surface↗
PubMedDate not supplied

Homocysteine and antiphospholipid antibodies in rheumatoid arthritis patients: relationships with thrombotic events.

OBJECTIVE: To investigate the possible relationships between plasma homocysteine levels and thrombotic events in a select population of rheumatoid arthritis (RA) patients with or without antiphospholipid (aPL) antibody positivity. METHODS: 168 female RA patients attending the Extra-articular Involvement RA Clinic of University of Genova and 72 female subjects matched for age and vascular diseases as controls were included in the study. 30 of the RA patients showed aPL antibody positivity and 138 aPL antibody negativity on the basis of the concomitant presence or absence of high concentrations of anticardiolipin (aCL) antibodies or the presence of lupus anticoagulant (LA). All subjects were evaluated for plasma homocysteine concentrations and for the occurrence of thrombotic events. RESULTS: Twenty-five RA patients and 5 controls reported a history of thrombotic events. Eleven and 5 of RA patients were found to have been previously affected by venous or arterial thrombosis, respectively. Plasma levels of homocysteine in aPL antibody positive patients with thrombosis were found to be significantly higher than in aPL antibody positive RA patients without thrombosis (p < 0.001). When RA patients with thromboses were analyzed, a significant increase of plasma homocysteine levels was found in aPL antibody-positive RA patients versus aPL antibody-negative RA patients (p < 0.04) and versus related controls (p < 0.003). CONCLUSIONS: The association observed between aPL antibody positivity and high levels of plasma homocysteine in RA patients may represent a possible risk factor for thrombotic events. Therefore, it is suggested that hyperhomocysteinemia might be involved in the vascular-related mortality observed in RA patients with a history of thrombosis.

Antibodies, Anticardiolipin↗
PubMedDate not supplied

Long-term treatment of patients affected by systemic sclerosis with cyclosporin A.

The aims of the present study were: 1) to verify the tolerability of long-term, low-dose treatment of patients affected by systemic sclerosis with cyclosporin A; 2) to analyze the clinical outcome of treated patients in relationship to skin, esophageal, lung, kidney and microvascular organ involvement. Nine patients affected by diffuse systemic sclerosis were treated for periods ranging from 3 to 5 years with cyclosporin A at a dosage of 2.5 mg/kg/day. Cyclosporin A treatment was variably associated or not with treatments for Raynaud's phenomenon (pentoxiphylline, defibrotide, low-dose heparin, prostacyclin analogues) in relationship to the needs of single patients. We report on patient clinical evaluations performed every year and including plicometry, esophageal pH-manometry, pulmonary spirometry, renal duplex Doppler sonography, echocardiography as well as nailfold videocapillaroscopy. The results of single tests were converted into scores. The existence of statistically significant differences between baseline mean scores and mean scores after 1, 2 and 3 years of therapy was analyzed. All patients tolerated cyclosporin A well, and no definitive withdrawals from the study were observed. Hypertricosis appeared in 3 patients, and 1 patient interrupted treatment for 6 months because of the onset of pneumonitis. No alterations of blood pressure and renal functionality were detected. Statistically significant reduction of all analyzed mean scores was observed after 2 and/or 3 years of cyclosporin A treatment with respect to baseline. The overall results suggest an encouraging clinical effect for low-dose, long-term cyclosporin A treatment in systemic sclerosis. Satisfactory tolerability and clinical improvement were observed in all the patients consecutively treated for at least 3 years.

Adult↗
PubMedDate not supplied

[Diagnostic perspectives in the rheumatologic vasculitis: the role of video-capillaroscopy].

Microvascular involvements represent one of the first step in many autoimmune diseases such as scleroderma (SSc) or antiphospholipid syndrome. Early in the disease, the peripheral microangiopathy may be well recognised and studied by nailfold videocapillaroscopy (NVC), a noninvasive and safe technique, that is reported to have both diagnostic and prognostic value, especially in the presence of Raynaud's phenomenon (RP). The classification of defined major NVC patterns in SSc might be useful in assessing the appearance and progression of the sclerodermic microangiopathy. In addition, the NVC changes might represent a morphological reproduction of the evolution of the SSc. The early appearance of giant capillaries and haemorrhages (Early pattern) is of great relevance for the early diagnosis of the SSc. Therefore, these alterations are more evident in the active phase of the disease (Active pattern). Conversely, the NVC observation of loss of capillaries, vascular architectural disorganisation and the presence of ramified/bushy capillaries (Late pattern) represents the clearest aspect of advanced SSc microvascular damages. Interesting, correlations between the NVC and clinical aspects of SSc, as well as the effects of therapeutical interventions have been observed.

Capillaries↗
PubMedDate not supplied

Methotrexate in psoriatic arthritis.

Methotrexate (MTX) is a folic acid analogue with antiproliferative and antiinflammatory effects. In the past several years, MTX has become the most commonly used agent in patients with severe, destructive psoriatic arthritis (PsA), with positive clinical results. Liver changes and serum enzyme level increases do not seem to be a major problem in PSA patients treated with MTX. In addition, PSA patients treated with low-dose MTX were not associated with pulmonary fibrosis as evaluated by means of sensitive imaging techniques and pulmonary function tests. The concomitant use of folic acid reduces both the frequency of serum liver enzyme level increases but also the efficacy of MTX by competing with the folate receptors.

Antirheumatic Agents↗
PubMedDate not supplied

Changes in fibronectin production in rat liver during cirrhotic evolution due to treatment with CCl4 and steroid hormones: correlation with plasmatic fibronectin.

Previous our studies showed that some steroid hormones, as pure crystalline Progesterone (pPc) and 17-alpha-hydroxyprogesterone capronate (17 alpha HPC) heightened the cirrhogenic action produced in rat liver by carbon tetrachloride. Medroxyprogesterone (MPA), however, did not appear to promote cirrhosis, but increased just steatosis. In the present paper, we have studied the above mentioned steroid hormones for their possible capability of inducing changes in plasma fibronectin concentration. For this purpose, the soluble plasma fibronectin level was measured in female rats 45 days after CCl4-induced cirrhosis, and it was compared with the insoluble fibronectin of liver (detected by immunostaining) and the collagen content in the organ. The results obtained show that, after treatment with CCl4 and MPA, both plasma and liver fibronectin content strongly increases, whereas liver collagen content lowers. However, after treatment with CCl4 alone or in association with the other two steroid hormones, any changes in fibronectin content is not observable, but, on the contrary, is evident a heightened collagen production associated with a cirrhotic change of liver.

17 alpha-Hydroxyprogesterone Caproate↗
PubMedDate not supplied

New roles for estrogens in rheumatoid arthritis.

Sex hormones appear to play an important role as modulators of autoimmune disease onset/perpetuation. Steroid hormones are implicated in the immune response, with estrogens as enhancers at least of humoral immunity, and androgens and progesterone (and glucocorticoids) as natural immune suppressors. Serum levels of estrogens have been found to be normal in rheumatoid arthritis (RA) patients. Synovial fluid levels (SF) of proinflammatory estrogens relative to androgens are significantly elevated in both male and female RA patients as compared to controls, which is most probably due to an increase in local aromatase activity. Thus, available steroid pre-hormones are rapidly converted to proinflammatory estrogens in the synovial tissue in the presence of inflammatory cytokines (i.e. TNF alpha, IL-1, IL-6). The increased estrogen concentrations observed in RA SF of both sexes are characterized mainly by the hydroxylated forms, in particular 16 alpha-hydroxyestrone, showing a mitogenic stimulating role. Indeed, recent studies by us indicate that 17-beta estradiol (E2) clearly enhanced the expression of markers of cell growth and proliferation, whereas testosterone (T) induced an increase in markers indicating DNA damage and apoptosis. In particular, our data further shows that the enhancing role of estrogens on the immune/inflammatory response is exerted by activating the NFkB complex. In conclusion, locally increased estrogens may exert activating effects on synovial cell proliferation, including macrophages and fibroblasts, suggesting new roles for estrogens in RA.

Adult↗
PubMedDate not supplied

Effects of DMARDs on IL-1Ra levels in rheumatoid arthritis: is there any evidence?

Recent research has shown that in the processes of rheumatoid arthritis (RA), interleukin-1 (IL-1) is one of the pivotal cytokines in initiating and driving the disease, and the body's natural response, IL-1 receptor antagonist (IL-1Ra), has been shown conclusively to block its effects. Several agents used to treat RA such as disease modifying antirheumatic drugs (DMARDs), as well as glucocorticoids (GC), affect the transcription, synthesis, release, and/or activity of cytokines, including the IL-1Ra. A higher ratio of IL-1Ra:IL-1 production by the peripheral blood mononuclear cells (PBMC) of RA patients successfully treated with methotrexate (MTX) is observed when compared with the PBMC of untreated patients or healthy controls. Recent studies have also shown a significant increase in IL-1Ra with low-dose MTX treatment of cultured monocytic cells. Antimalarials (hydroxychloroquine and chloroquine) have been found to increase the monocyte production of IL-1Ra and these changes might explain at least some of their mechanisms of action. Various studies have shown that leflunomide (LF) tends to favor the inhibition of pro-inflammatory and matrix-destructive factors over that of anti-inflammatory factors (i.e. IL-1Ra) and metalloproteinase inhibitors, thus interfering with both inflammation and tissue destruction. Further studies should investigate the effects of LF on synovial tissue/fluid expression of the IL-1Ra in treated RA patients. Regarding cyclosporin A (CyA), considerable evidence shows that the treatment of RA patients induces a decrease in IL-1Ra levels. Similar results with the inhibition of IL-1Ra mRNA and protein have been observed following RA treatment with glucocorticoids. In addition, the oral administration of cortisol to normal subjects also decreased LPS-induced IL-1Ra synthesis in cultured monocytes. The effects of different DMARDs and GC on IL-1Ra levels in RA patients, as reviewed in this paper, support the important role that selected anticytokine treatments might exert in the pathophysiology of the disease.

Antirheumatic Agents↗
PubMedDate not supplied

Is there a rationale to using leflunomide in early rheumatoid arthritis?

The efficacy of leflunomide in the treatment of early rheumatoid arthritis (RA) patients might be attributed to the fact that it acts at several levels, including the anti-inflammatory and anti-destructive pathways. This is in addition to its inhibition of the L-dihydro-orotate dehydrogenase (DHOH) enzyme and pyrimidine de novo synthesis which decreases cell proliferation and more specifically early activated CD4+ T cells, as well as monocyte interaction with T cells leading to cytokine and anticytokine production. Recent studies clearly indicate the rationale of an early administration of leflunomide in RA patients, particularly in the light of the results of previously reported clinical studies showing its rapid onset of action when compared to other DMARDs. The early efficacy and safety of leflunomide in patients with early RA is sustained over a long period, and the long-term safety profile of leflunomide does not seem to be different from that observed in phase III trials.

Anti-Inflammatory Agents↗
PubMedDate not supplied

Localized and systemic forms of scleroderma in adults and children .

Systemic sclerosis (SSc) presents a great deal of variability in the extent and severity of skin and internal organ involvement. The diagnostic and prognostic significance of autoantibodies in SSc is undisputed and the patient's autoantibody profile represents a fundamental tool for clinicians. Scleroderma is a rare condition in children. Unlike adults, localized scleroderma is more frequent than the systemic sclerosis, nevertheless it represents a disabling condition. In both conditions, no validated outcome measures and proven effective treatment is available to date.Raynaud's phenomenon (RP) is one the most common and significant clinical symptoms of SSc and therefore in patients with RP a capillaroscopic analysis should be carried out as soon as possible. The actual and select advantage of the early nailfold videocapillaroscopic (NVC) analysis is to distinguish between the primary RP and the secondary RP and to allow the early detection of SSc.

Adult↗
PubMedDate not supplied

Recommendations for the use of biologic (TNF-alpha blocking) agents in the treatment of rheumatoid arthritis in Italy.

The present report is devoted to drawing up and disseminating specific recommendations for the use of anti-TNF-alpha therapies in patients with rheumatoid arthritis (RA) in Italy. The document reports and discusses the published literature concerning the criteria for inclusion, assessment of response and for withdrawal of treatment with TNF blocking agents in RA. Several specific points concerning more sensitive warnings are discussed: tuberculosis, hepatitis, lymphoma, and cardiovascular risk and induction of autoimmunity. The recommendations are summarized in an 8-point table approved by the executive committee of the Italian Society for Rheumatology.

Antibodies, Monoclonal↗
PubMedDate not supplied

[Macroglobulin alpha-2 in synovial fluid: relationship with reactants of the acute phase of rheumatoid arthritis].

Metalloproteinases (e.g. collagenase, elastase, stromelysin) are present in large amount in synovial fluid (SF) during rheumatoid arthritis (RA) and are actively involved in articular tissue damage. alpha 2-Macroglobulin (alpha 2M) functions as a "molecular trap" for proteinases and is considered the major inhibitor of metalloproteinases. We found increased concentrations of alpha 2M in SF of RA patients, significantly related to acute phase reactants, local inflammatory parameters and joint damage. The alpha 2M ratio between, RA SF and control SF, was found higher than between RA serum and control serum, indicating a selective localization and activity of alpha 2M in inflamed joint. The relationship between alpha 2M and the inflammatory parameters, including IL-6, is discussed.

Acute Disease↗
PubMedDate not supplied

Circannual vitamin d serum levels and disease activity in rheumatoid arthritis: Northern versus Southern Europe.

BACKGROUND: Greater intake of vitamin D has been associated with a lower risk of rheumatoid arthritis (RA) and low serum vitamin D together with higher prevalence of RA seem common among North European people when compared to Southern Europe. OBJECTIVES: To evaluate serum 25-hydroxyvitamin D [25(OH)D] levels in female RA patients from North (Estonia) and South (Italy) Europe and to correlate them with the disease activity score (DAS28) during winter and summer. METHODS: Fifty-four RA Italian patients (IP) and 64 RA Estonian patients (EP) were evaluated for serum 25(OH)D levels in winter and summer time, as well as for DAS28 score. Normal female controls (C) were 35 (IC) and 30 (EC) age-matched subjects, respectively. 25(OH)D concentrations were measured by a competitive radioimmunoassay. Statistical analysis was performed by "r" Pearson correlation, "t" Student with Bonferroni correction and by repeated ANOVA measures (summer and winter) with two factors (country and clinical status). RESULTS: 25(OH)D levels were found significantly higher in IP versus EP (p = 0.0116) both in winter and in summer time. Differences were observed also in controls. The variations (increase) of 25(OH)D levels between winter and summer were found significant (p = 0.0005) in both IP and EP. Differences were observed also in controls. No significant differences were found concerning 25(OH)D levels between RA patients and their controls in either country. Interestingly, a significant negative correlation between 25(OH)D and DAS28, was found in summer only in IP (r =-0.57, p < 0.0001) and in winter in EP (r =-0.40, p < 0.05). CONCLUSION: Significantly lower 25(OH)D serum levels were observed in RA patients from North versus South Europe with a circannual rhythm in winter and summer time. In addition, 25(OH)D values showed a significant correlation (negative) with RA clinical status (DAS28) in both North and South European RA patients, suggesting possible effects of vitamin D among other factors on disease activity.

Aged↗