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B Seriolo

Publications and source records attributed to B Seriolo.

At least 19 recordsLinked to original sources
PubMed2006

Serum cytokines and steroidal hormones in polymyalgia rheumatica and elderly-onset rheumatoid arthritis.

BACKGROUND: Polymyalgia rheumatica (PMR) may create some difficulties in the differential diagnosis of elderly-onset rheumatoid arthritis (EORA) and of EORA with PMR-like onset (EORA/PMR). AIM: To investigate possible differences between three groups of patients, with regard to serum levels of inflammatory cytokines and steroidal hormones at baseline and after 1 month of treatment with glucocorticoids (prednisone 7.5-12.5 mg/day). PATIENTS AND METHODS: 14 patients with PMR, 15 with EORA and 14 with EORA/PMR, as well as 15 healthy, matched controls were analysed. Tumour necrosis factor alpha (TNFalpha), interleukin (IL)6, IL1 receptor antagonist (IL1Ra), cortisol, dehydroepiandrosterone sulphate (DHEAS) and 17-hydroxy-progesterone (PRG) were evaluated. RESULTS: Serum levels of both TNFalpha and IL6 were significantly higher in all three groups of patients than in controls (p<0.01). Serum IL6 levels were significantly higher in patients with both PMR and EORA/PMR than in patients with EORA (p<0.05). IL1Ra serum levels were significantly higher in patients with EORA than in controls (p<0.001) and in patients with PMR and EORA/PMR (p<0.05). DHEAS was significantly lower in patients with EORA/PMR than in those with EORA (p<0.05). PRG was significantly higher in all patient groups (p<0.05). After glucocorticoid treatment, serum TNFalpha and IL6 levels significantly decreased in all patient groups; IL1Ra significantly increased in patients with PMR and in those with EORA/PMR; cortisol, DHEAS, and PRG significantly decreased in patients with PMR and in those with EORA/PMR (p<0.05). CONCLUSIONS: Different cytokine and steroidal hormone patterns suggest that patients with PMR and those with EORA/PMR seem to be have a more intensive inflammatory reaction and are more efficient responders to glucocorticoid treatment than patients with EORA.

17-alpha-Hydroxyprogesterone↗
PubMed2005

Anti-inflammatory effects of leflunomide in combination with methotrexate on co-culture of T lymphocytes and synovial macrophages from rheumatoid arthritis patients.

OBJECTIVES: To investigate the anti-inflammatory effects of the active leflunomide metabolite A771726 (Lef-M) in combination with methotrexate (MTX) on synovial macrophages (SM) from rheumatoid arthritis (RA) patients co-cultured with an activated T cell line (Jurkat cell line). METHODS: Pro-inflammatory cytokines (TNFalpha, IL1beta, IL6), adhesion molecule ICAM-1, cyclooxygenase isoenzymes (COX1, COX2), and the nuclear factor kappaB (NF-kappaB) complex were analysed on SM co-cultured with a T cell line, as intracellular protein expression by immunocytochemistry (ICC) and western blot analysis, as extracellular protein expression by ELISA assay, and as mRNA expression by reverse transcriptase-multiplex PCR (RT-MPCR) after treatment with Lef-M (1, 10, 30 micromol/l) alone or in combination with MTX (50 ng/ml). RESULTS: The most significant intracellular decrease in cytokines was observed by ICC in SM treated with the combination of Lef-M (1, 10, 30 micromol/l) and MTX (50 ng/ml) versus untreated SM (TNFalpha 29%, 37%, 49%, IL1beta 56%, 43%, 50%, and IL6 59%, 62%, 71%, respectively). Furthermore, a significant decrease was confirmed concerning cytokine levels evaluated by ELISA in the medium of SM treated with the combination Lef-M+MTX (TNFalpha 40%, 41%, 44%; IL1beta 10%, 20%, 60%; IL6 37%, 41%, 49%, respectively). Western blot and RT-PCR analysis confirmed these results. Concordant decreased expression was observed for ICAM-1, COX1, COX2, and the NF-kappaB complex after Lef-M+MTX treatment. CONCLUSIONS: The combination of MTX and Lef-M shows additive inhibitory effects on the production of inflammatory mediators from SM co-cultured with a T cell line. These observations might support the positive results obtained in RA clinical studies by combination therapy.

Analysis of Variance↗
PubMed2005

Altered circadian rhythms in rheumatoid arthritis patients play a role in the disease's symptoms.

The circadian changes in the metabolism or nocturnal secretion of endogenous corticosteroids (reduction) observed in rheumatoid arthritis (RA) patients are responsible, in part, for the time-dependent changes that are observed in the inflammatory response and related early morning clinical symptoms of the disease. Melatonin (MLT), another circadian nocturnal hormone that is the secretory product of the pineal gland, has been implicated in the time-dependent RA inflammatory reaction with effects that are opposite to those of corticosteroids. As a consequence, altered functioning of the HPA axis (early morning reduced corticosteroid production) and of the pineal gland (night increased MLT production) found in RA patients, seem to be important factors in the appearance and perpetuation of the clinical circadian symptoms of the disease. Consistently, human proinflammatory Th1-type cytokine production (related to MLT stimulation) exhibits a diurnal rhythmicity with peak levels during the night and early morning, at a time when plasma cortisol (inducing the Th2-type cytokine production) is lowest and MLT is highest. Reduced daily light exposure as observed in northern Europe (Estonia), at least during the winter, might explain the higher and more prolonged serum MLT concentrations that were observed in northern RA patients, as well as some epidemiological features versus southern Europe patients.

Arthritis, Rheumatoid↗
PubMed2005

Estrogens, autoimmunity and the heart.

Systemic inflammatory/autoimmune rheumatic diseases are associated with a significantly increased rate of atherosclerosis and cardiovascular disease. Several mechanisms of accelerated atherosclerosis have been proposed, including abnormal lipid and lipoprotein profiles, oxidative stress, enhanced apoptosis, thrombophilia, immune complexes and increased mononuclear cell infiltration of atherosclerotic lesions, local generation of cytokines and female estrogen deficiency. However, the widely shared enthusiasm about the cardioprotective potential of hormone replacement therapy (HRT) with estrogens, has come to an abrupt halt since very recent randomized trials failed to show a cardiovascular risk reduction in postmenopausal women. Several factors might play a role in these discrepancies, in particular, parts of the striking discrepancy between observational and randomized data have been attributed to an estrogen-mediated adverse effect on inflammation (enhancement, possibly dose-related). In fact, estrogens potentially increase the inflammatory/immune response in autoimmune rheumatic diseases. New roles for estrogen peripheral metabolites (hydroxylated) and their increased formation in inflammatory sites, might partially introduce some explanations for several apparently contrasting evidences.

Animals↗
PubMed2004

Nailfold videocapillaroscopic patterns and serum autoantibodies in systemic sclerosis.

BACKGROUND: Microvascular lesions are a predominant feature in systemic sclerosis (SSc) and seem to play a central pathogenetic role. Recently, we graded scleroderma microangiopathy by nailfold videocapillaroscopy (NVC) into three NVC patterns (early, active and late). The aim of the present study was to confirm, in a larger number of SSc patients, the presence of three patterns of microvascular damage, and to detect any possible relationship between these patterns and both specific serum autoantibodies and the subsets of cutaneous involvement. METHODS: Two hundred and forty-one consecutive patients (227 women and 14 men) affected by SSc were recruited. One hundred and forty-eight patients were affected by limited cutaneous SSc (lSSc) and 93 patients by diffuse cutaneous SSc (dSSc). The ages at onset of Raynaud's phenomenon (RP) and SSc, the durations of RP and SSc, ANA and antitopoisomerase I (anti-Scl70) and anticentromere (ACA) antibodies were investigated in all patients. The SSc patients were subdivided on the basis of the NVC pattern into three groups. RESULTS: A statistically significant correlation was found between the NVC patterns and the durations of both RP and SSc (P<0.001). Enlarged and giant capillaries, together with haemorrhages, constituted the earliest NVC finding in SSc (early NVC pattern). These abnormalities were mostly expressed in the active NVC pattern. Loss of capillaries, ramified capillaries and vascular architectural disorganization were increased in the late NVC pattern. Age and the duration of both RP and SSc were lower in 24 patients complaining of RP alone. Anti-Scl70 antibodies were statistically less frequent in the early vs both the active and the late NVC pattern, whereas no significant correlation was found between the presence of anti-Scl70 antibodies and the duration of either RP or SSc. ACA positivity was more frequent in patients with longer RP duration. Patients with lSSc had shorter SSc duration and showed the early or active NVC pattern more frequently. Conversely, patients with dSSc showed longer disease duration and mostly showed the late NVC pattern. CONCLUSIONS: NVC is an appropriate tool for differential diagnosis between primary and secondary RP through the clear recognition of the early NVC scleroderma pattern. This study confirms, in a large number of SSc patients, the existence of three distinct NVC patterns that might reflect the evolution of SSc microangiopathy. The presence of anti-Scl70 antibodies seems be related to earlier expression of the active and late NVC patterns of SSc microvascular damage. The presence of ACA seems to be related to delayed expression of the late NVC pattern.

Adult↗
PubMed2004

Sex hormones influence on the immune system: basic and clinical aspects in autoimmunity.

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

Androgens↗
PubMed2003

[Rheumatoid arthritis and atherosclerosis].

Evidence continue to accumulate indicating that patients with rheumatoid arthritis (RA) present an increased risk of cardiovascular disease (and death). The risk factors for coronary artery disease (CAD) in RA are not fully understood. However, a number of possible factors have been described, but more than one may be efficient, such as homocysteine, presence of antiphospholipid antibodies, altered serum levels of selected lipoproteins, and all together may have implications for the atherogenesis observed in these patients. Other factors that may facilitate this process, include corticosteroid use, methotrexate therapy and hormonal factors. However, the relative importance of these specific risk factors for the atherogenesis in this disease is poorly known. Recent findings indicate that cardiac death is increased in RA patients when compared with subjects without arthritis and that generally, the inflammatory process may contribute to atherosclerosis. In addition, other studies indicate that serum concentration of pro-inflammatory cytokines are found elevated at baseline, among patients at risk for future coronary occlusion.

Antiphospholipid Syndrome↗
PubMed2002

Eradication of Helicobacter pylori may reduce disease severity in rheumatoid arthritis.

BACKGROUND: A triggering infectious agent has long been postulated in rheumatoid arthritis. Data on the possible role of Helicobacter pylori infection are lacking. AIM: To assess the effect of H. pylori eradication in patients with rheumatoid arthritis. METHODS: Fifty-eight adult patients with established rheumatoid arthritis and dyspeptic symptoms were recruited - 28 were H. pylori-positive and 30 were H. pylori-negative on the basis of invasive tests. All infected patients were treated successfully. We evaluated the disease activity using clinical and laboratory parameters at baseline and every 4 months during 2 years, and compared the variations in the two subgroups. RESULTS: H. pylori-eradicated rheumatoid arthritis patients showed progressive improvement over time (P < 0.0001) of all clinical indices compared with baseline, whereas H. pylori-negative rheumatoid arthritis patients remained substantially unchanged. After 2 years, H. pylori-eradicated rheumatoid arthritis patients differed significantly (P < 0.04-0.0001) from patients without H. pylori infection in terms of improvement of all clinical parameters. At the same time point, several laboratory indices (erythrocyte sedimentation rate, fibrinogen, alpha2-globulins and antinuclear antibody) showed significantly lower values (P < 0.02-0.0003) in the H. pylori-eradicated subgroup compared to the H. pylori-negative subgroup. CONCLUSIONS: Our data suggest that H. pylori infection is implicated in the pathogenesis of rheumatoid arthritis, in that its eradication may induce a significant improvement of disease activity over 24 months. H. pylori eradication seems to be advantageous in infected rheumatoid arthritis patients, but controlled studies are needed.

Adult↗
PubMed2002

Cortisol, dehydroepiandrosterone sulfate, and androstenedione levels in patients with polymyalgia rheumatica during twelve months of glucocorticoid therapy.

This paper aims to evaluate adrenal gland hormone levels in patients with polymyalgia rheumatica (PMR) during glucocorticoid (GC) therapy. A lower than expected basal production of cortisol was found in active and glucocorticoid-untreated PMR patients, particularly females. The abrupt onset of PMR with clinical features similar to those of the steroid-withdrawal syndrome or adrenal insufficiency, as well as the clinical response to GC therapy in elderly people already age-disposed to an inadequate adrenal and anti-inflammatory response, might represent the most significant pathophysiological basis of the disease.

Adrenal Cortex↗
PubMed2002

Melatonin serum levels in rheumatoid arthritis.

The pineal hormone melatonin (MLT) exerts a variety of effects on the immune system. MLT activates immune cells and enhances inflammatory cytokine and nitric oxide production. Cytokines are strongly involved in the synovial immune and inflammatory response in rheumatoid arthritis (RA) and reach the peak of concentration in the early morning, when MLT serum level is higher. Nocturnal MLT serum levels were evaluated in 10 RA patients and in 6 healthy controls. Blood samples were obtained at 8 and 12 p.m., as well as at 2, 4, 6, and 8 a.m. MLT serum levels at 8 p.m. and 8 a.m. were found to be higher in RA patients than in controls (p < 0.05). In both RA patients and healthy subjects, MLT progressively increased from 8 p.m. to the first hours of the morning, when the peak level was reached (p < 0.02). However, MLT serum level reached the peak at least two hours before in RA patients than in controls (p < 0.05). Subsequently, in RA patients, MLT concentration showed a plateau level lasting two to three hours, an effect not observed in healthy controls. After 2 a.m., MLT levels decreased similarly in both RA patients and healthy subjects. Several clinical symptoms of RA, such as morning gelling, stiffness, and swelling, which are more evident in the early morning, might be related to the neuroimmunomodulatory effects exerted by MLT on synovitis and might be explained by the imbalance between cortisol serum levels (lower in RA patients) and MLT serum levels (higher in RA patients).

Adult↗
PubMed2000

The hypothalamic-pituitary-adrenocortical and gonadal axis function in rheumatoid arthritis.

The altered cortisol and adrenal androgen (i.e., dehydroepiandrosterone sulfate = DHEAS) secretion, observed during testing in rheumatoid arthritis (RA) patients not treated with corticosteroids, should be clearly regarded as a "relative adrenal insufficiency" in the setting of a sustained inflammatory process, as shown by high serum IL-6 levels. Androgens seem implicated in the pathophysiology of autoimmune disorders, including RA, as natural immunosuppressors. Low plasma and synovial fluid testosterone concentrations are observed in male RA patients; low plasma DHEAS levels are mainly observed in female RA patients. The menopausal peak of RA suggests that estrogens and/or progesterone deficiency also play a role in the disease, and many data indicate that estrogens suppress cellular immunity, but stimulate humoral immunity (i.e., deficiency promotes cellular Th1-type immunity). Gene polymorphisms for enzymes involved in the steroidogenesis seem to further complicate the role of sex hormones in the susceptibility to autoimmunity. Acquired changes of sex steroid metabolism seem to also play a role in the peripheral sex hormone levels. In conclusion, a complex interaction between the hypothalamus-pituitary-adrenocortical and gonadal axis functions is evident in RA.

Adrenal Insufficiency↗
PubMed2000

Evidence of cerebral hypoperfusion in scleroderma patients.

OBJECTIVES: To investigate regional cerebral blood flow by (99m)Tc-hexamethylpropylenamineoxime (HMPAO) single photon emission computed tomography (SPECT) in a series of 40 patients (mean age 58.5+/-11.5 yr) affected by systemic sclerosis (SSc) in comparison with age-matched healthy controls. METHODS: Subjects affected by concomitant severe pathologies that might interfere with the interpretation of the SPECT results were excluded. SPECT findings were correlated with the severity of peripheral microvascular involvement, as assessed by nailfold videocapillaroscopy (NVC). Whenever possible, patients underwent magnetic resonance imaging (MRI) of the brain. RESULTS: Twenty-one SSc patients (52%) showed hypoperfusion in two or more regions of interest (ROIs) at the SPECT analysis. MRI was available in 14 of these patients, and was shown to be altered in eight of them (57%). One patient with both abnormal SPECT and abnormal MRI was affected by mild cognitive impairment. Transcranial Doppler sonography was normal in all but one of these patients with hypoperfusion. Nineteen patients exhibited a normal brain SPECT scan, but the MRI was shown to be altered in 3/12 of them (25%). No significant differences were found between the group of SSc patients showing hypoperfusion and those showing a normal SPECT scan regarding age, the duration of disease, the presence of vascular risk factors or damage of other organs typically involved in the disease, and the severity of peripheral microvascular involvement (NVC). CONCLUSIONS: Focal or diffuse cerebral hypoperfusion was found in more than half of the neurologically asymptomatic SSc patients studied, paralleling the incidence of altered brain MRI. The hypoperfusion was not linked to ageing and possibly reflects the cerebral location of the microangiopathic process characterizing the disease.

Adult↗
PubMed2000

The hypothalamic-pituitary-adrenal and gonadal axes in rheumatoid arthritis.

The hypothalamic-pituitary-adrenal (HPA) and the hypothalamic-pituitary-gonadal (HPG) axes involvement or response to immune activation seems crucial for the control of excessive inflammatory and immune conditions such as autoimmune rheumatic diseases, including rheumatoid arthritis (RA). However, female patients seem to depend more on the HPA axis, whereas male patients seem to depend more on the HPG axis. In particular, hypoandrogenism may play a pathogenetic role in male RA patients because adrenal and gonadal androgens, both products of the HPA and HPG axes, are considered natural immunosuppressors. A significantly altered steroidogenesis of adrenal androgens (i.e., dehydroepiandrosterone sulfate, DHEAS and DHEA) in nonglucocorticoid-treated premenopausal RA patients has been described. The menopausal peak of RA suggests that estrogens and/or progesterone deficiency also play a role in the disease, and many data indicate that estrogens suppress cellular immunity, but stimulate humoral immunity (i.e., deficiency promotes cellular Th1-type immunity). A range of physical and psychosocial stressors are also implicated in the activation of the HPA axis and related HPG changes. Chronic and acute stressors appear to have different actions on immune mechanisms with experimental and human studies indicating that acute severe stressors may be even immunosuppressive, while chronic stress may enhance immune responses. The interactions between the immunological and neuroendocrine circuits is the subject of active and extensive ongoing research and might in the near future offer highly promising strategies for hormone-replacement therapies in RA.

Animals↗
PubMed2000

[Can Helicobacter pylori infection be a risk factor for the severity of rheumatoid arthritis?].

AIM: In this study we assessed the effect of Helicobacter pylori eradication in patients with established rheumatoid arthritis (RA) in order to show a possible pathogenetic role of the infection in this disease. METHODS: We recruited 31 patients with variable RA activity. Of them, 15 were Hp-positive (12 F and 3 M, mean age 55 +/- 10.6 years) and 16 Hp-negative (13 F and 3 M, mean age 54.2 +/- 9.1 years) on the basis of the concomitant positive or negative findings of both CLO-test and histology performed on both antral and corpus biopsies. The infected group was treated and the bacterium was considered eradicated when both tests were negative a month after therapy. We have evaluated the disease activity at baseline and during a total follow-up period of 16 months with check-points every 4-months and compared clinical and laboratory findings between the Hp-negative and the eradicated groups. Both groups were being treated with NSAIDs and prednisolone (< or = 7.5 mg/die) or its equivalents. RESULTS: Hp-eradicated RA patients showed a progressive improvement overtime (p = 0.0009) of all clinical indices compared with baseline, while Hp-negative RA patients did not. At the 16-month checkpoint, the eradicated RA patients differed significantly (p < 0.006) from patients without Hp infection by all indices, except grip strength of the hands. Also all laboratory data improved significantly from baseline to the 16 month checkpoint (p < 0.03) within the Hp-eradicated group and between the two groups of eradicated and Hp-negative RA patients (p < 0.0007) except for Hb, aCL IgM and gamma-globulins. CONCLUSIONS: Our data suggest that Hp infection is implicated in the pathogenesis of RA. On the basis of our data, the eradication of Hp should be recommended in infected RA patients.

Aged↗