[show abstract][hide abstract] ABSTRACT: Fibromyalgia (FM) is characterized by the presence of chronic widespread pain throughout the musculoskeletal system and diffuse tenderness. Unfortunately, no laboratory tests have been appropriately validated for FM and correlated with the subsets and activity. The aim of this study was to apply a proteomic technique in saliva of FM patients: the Surface Enhance Laser Desorption/Ionization Time-of-Flight (SELDI-TOF). For this study, 57 FM patients and 35 HC patients were enrolled. The proteomic analysis of saliva was carried out using SELDI-TOF. The analysis was performed using different chip arrays with different characteristics of binding. The statistical analysis was performed using cluster analysis and the difference between two groups was underlined using Student's t-test. Spectra analysis highlighted the presence of several peaks differently expressed in FM patients compared with controls. The preliminary results obtained by SELDI-TOF analysis were compared with those obtained in our previous study performed on whole saliva of FM patients by using electrophoresis. The m/z of two peaks, increased in FM patients, seem to overlap well with the molecular weight of calgranulin A and C and Rho GDP-dissociation inhibitor 2, which we had found up-regulated in our previous study. These preliminary results showed the possibility of identifying potential salivary biomarker through salivary proteomic analysis with MALDI-TOF and SELDI-TOF in FM patients. The peaks observed allow us to focus on some of the particular pathogenic aspects of FM, the oxidative stress which contradistinguishes this condition, the involvement of proteins related to the cytoskeletal arrangements, and central sensibilization.
[show abstract][hide abstract] ABSTRACT: In our previous study, we observed that the presence of autoimmune thyroid disease worsens fibromyalgia (FM) symptoms. The aims of this study are to evaluate whether there is a predisposition for the development of FM in patients with Hashimoto's thyroiditis (HT) with or without subclinical hypothyroidism (SCH) and in patients with SCH alone and what is the weight of antithyroid antibody positivity and SCH on FM comorbidity. Fifty-two patients, 39 affected by HT with or without SCH and 13 by SCH, were matched with 37 patients affected by FM and 25 healthy subjects. Blood samples were collected from all study subjects for the determination of serum TSH, free triiodothyronine, free thyroxine, antithyroperoxidase antibody (TPOAb), antithyroglobulin antibody (TgAb) and non-organ-specific autoantibodies. Clinical assessment of patients and controls included the "Fibromyalgia Impact Questionnaire" (FIQ), while pain severity was evaluated using a visual analogue scale (VAS). Patients and controls were also characterized by the presence of diffuse pain, fatigue, paresthesiae, muscle spasms, non-restful sleep, tension headache and presence of mood disorders. FM comorbidity resulted in twelve HT subjects (31%) and none in SCH patient. In particular, FM comorbidity in HT patients without SCH was 33.3% and in HT patients with SCH was 28.5%. Based on our data, we speculate that maybe there is more than a hypothesis regarding the cause-effect relation between thyroid autoimmunity and the presence of FM, thus suggesting a hypothetical role of thyroid autoimmunity in FM pathogenesis.
Rheumatology International 11/2010; 32(2):335-41. · 2.21 Impact Factor
[show abstract][hide abstract] ABSTRACT: Increasing evidence has been accumulated for treating rheumatoid arthritis (RA) with TNF-α blocking agents. The formulation and definition of an early indicator of patient's reactivity during therapy may be extremely simplified by a mathematical model of clinical response. We analyzed the most significant clinical and laboratory parameters of response of 35 homogeneous patients (30 women, 5 men mean age ± SD: 52.31 ± 12.30 years) treated with adalimumab 40 mg every 2 weeks associated with methotrexate (MTX) 10-15 mg/week and with a stable dosage of steroids for 30 weeks. The over time trend of the studied parameters showed a linear response, which has allowed the realization of a simple mathematical model. The formula derived from this mathematical model was then applied and therefore validated in a group of 121 patients previously treated with several anti-TNF-alpha agents for at least 6 months. We drafted a mathematical model (early response indicator, ERI) that, by using a simple calculation, allows us to identify a high percentage of responder patients after only 2 weeks of treatment. ERI identified a high percentage (88%) of patients responding after only 2 weeks, as was confirmed at weeks 30; the use of ERI calculation after 6 weeks increases the proportion of responding patients to 92% with a percentage of false negatives of only 12%. ERI could be a useful tool to early differentiate the responder from the non-responder patients.
Rheumatology International 11/2010; 32(2):349-56. · 2.21 Impact Factor
[show abstract][hide abstract] ABSTRACT: The aim of this study was to investigate the clinical features of stomatognathic dysfunction in patients with rheumatoid arthritis (RA). The study sample consisted of 40 patients with RA (34 female, 6 male), mean age 44 years, recruited at the Rheumatology Division of the Department of Internal Medicine, University of Pisa, Italy. The inclusion criteria were diagnosis of RA according to the criteria of the American Rheumatism Association (ARA). In the study, 82.5% (n=33) of patients affected by RA satisfied at least the criteria of one diagnosis of temporomandibular disorders (TMD), according to the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD). The results are in agreement with the literature and the prevalence of such involvement ranges between 53% and 94% of patients. Several studies reported an involvement of the stomatognathic system in RA. In fact, RA can affect the temporomandibular joint as much as any other synovial joint. A more thorough analysis is required for a multidisciplinary approach to gnathological patients, including assessment by a rheumatologist. This issue and its epidemiologic relevance need further scientific research. Dentistry has a fundamental role in this process since patients who present with a systemic disease such as RA can be recognized and intercepted and referred to medical specialists, i.e., rheumatologists, to provide a diagnosis and therapy.
Cranio: the journal of craniomandibular practice 07/2010; 28(3):181-6. · 1.11 Impact Factor
[show abstract][hide abstract] ABSTRACT: In the last few years, serum and joint synovial fluid have been extensively analyzed for the proteomic research of rheumatoid arthritis (RA) biomarkers. Nonetheless, to date, there have been no studies investigating salivary biomarkers in this condition. Therefore, aim of this study is to investigate the presence of potential biomarkers of RA in human whole saliva.
We combined 2-DE and MS to analyze the whole saliva protein profile of 20 RA patients in comparison with 20 sex- and age-matched healthy subjects.
Eight salivary proteins resulted differentially expressed, namely calgranulin A, calgranulin B, apolipoprotein A-1, 6-phosphogluconate dehydrogenase, peroxiredoxin 5, epidermal fatty acid-binding protein, 78 kDa glucose-regulated protein precursor (GRP78/BiP), and 14-3-3 proteins. It is particularly interesting that chaperone GRP78/BiP showed the greatest increase in RA patients. This finding was validated by Western Blot analysis and the over-expression of GRP78/BiP appear to be distinctive of RA and drugs treatment independent.
This study provides a rationale for further studies aimed at evaluating any correlation between GRP78/BiP and different clinical/serological aspects of the disease in order to improve the diagnostic algorithms of RA.
[show abstract][hide abstract] ABSTRACT: To evaluate the role of spasmophilia (SP) in fibromyalgia syndrome (FM).
Three hundred and fourteen patients (280 F, 34 M) with a diagnosis of FM or FM and spasmophilia (FM+SP) were recruited. Clinical assessment of patients and controls included the Questionnaires FIQ, HAQ and the tender point (TP) count. Life-time or ongoing psychiatric aspects were evaluated by trained psychiatrists by means of the classic scales: Structured Clinical Interview (SCID) for DSM-IV. The following analysis were evaluated: cytokine (IL1, IL2, IL6, IL8, IL10), TNF-α, cortisol, GH, ACTH, IGF1, 5HT, intracellular Mg, plasma calcium p(Ca), PTH, (25(OH)D) and thyroid functionality. Some typical symptoms were investigated.
Eighty-one patients resulted positive for spamophilia (FM+SP), while 233 resulted negative for spasmophilia (FM). The mean TP number resulted higher in the FM group (15.33±3.88) with respect to FM+SP (12.88±6.17, p=0.016), while FIQ and HAQ did not differ between the two studied groups. FM patients exhibited a higher frequency of psychiatric disorders with respect to FM+SP patients (72% FM vs. 49% FM+SP, p<0.01). In particular the frequency of depression was 65.5% FM vs. 35% FM+SP (p<0.01).
The presence of spasmophilia seems to influence psychiatric comorbidity which was less prevalent in FM+SP patients. FM is indeed characterised by an abnormal sensory processing of pain that seems to result from a combination of interactions between neurotransmitters, stress, hormones and the nervous system; spasmophilia would seem to be more linked to a dysfunction at the neuromuscular level.
[show abstract][hide abstract] ABSTRACT: Objective: to investigate how therapeutic mas-sage, combined with stretching, can really con-tribute to the treatment of fibromyalgia (FM) symptoms. Design: Feasibility study. Setting: A single center. Participants: Twenty women hav-ing a preexisting diagnosis of FM based on American College of Rheumatology criteria were recruited. Intervention: Subjects received a total of 18 sessions of light massage administered by a physical therapist twice a week and then per-formed passive stretching exercises. Main out-come measures: heart rate (HR) and Heart Rate variability (HRV), the assessment of joint flexi-bility through elettrogoniometer, the Fibromyal-gia Impact Questionnaire (FIQ), the Pittsburgh Sleep Quality Index (PSQI), and the Borg scale or Rating of Perceived exertion (RPE). Evalua-tions were conducted at the screening visit (T0), immediately at the end of the session of mas-sage (T1) and after completion of 18 sessions (T2). Results: HRV showed an improvement in terms of decreased sympathetic tone and in-crease of parasympathetic tone at the end of treatment. Also joint flexibility showed a sig-nificant improvement at T2 compared with the screening. FIQ, PSQI, RPE did not change. Conclusions: the findings highlight the excel-lent compliance of FM patients to the combined therapy of massage and stretching, showing an amelioration of muscle stiffness and an im-provement of autonomic nervous system with a decrease of sympathetic tone and an increase of parasympathetic tone. The questionnaires did not show any ameliorations, probably because in these patients the perception of quality of life is distorted compared with more objective pa-rameters, such as muscle rigidity, the articular mobility and the autonomic nervous system.
[show abstract][hide abstract] ABSTRACT: The aim of the present study was to evaluate the concentration of cell-free DNA (cf-DNA) in the plasma of patients with systemic sclerosis (SSc) and to examine the correlation of cf-DNA with clinical variables of the disease. The study population consisted of 122 SSc patients and 16 healthy controls. Epidemiological and clinical data were collected by direct assessment. The beta-globin gene was used to determine the total amount of DNA in the plasma by real-time quantitative PCR analysis. cf-DNA was found in all patients (mean concentration 1,420.7 copies/ml) and controls (mean concentration 1,462.5), with no significant difference. In SSc patients, no correlation was found between cf-DNA and the type of organ involvement, but patients with active disease presented significantly higher cf-DNA concentrations than those with inactive disease (p < 0.05). Our data suggest that cf-DNA could provide a useful biomarker for the assessment of disease activity in SSc patients.
[show abstract][hide abstract] ABSTRACT: Rheumatoid arthritis (RA) patients are characterized by increased arterial stiffness, an independent predictor of cardiovascular risk. It has been suggested that osteopontin (OPN), a cytokine involved in RA pathogenesis, might have vascular effects. To study a possible relationship between OPN and arterial stiffness, aortic pulse wave velocity (PWV) was measured by tonometry in 69 patients (41 with RA, 28 with systemic sclerosis [SSc]) and 18 healthy controls. Plasma OPN levels, oxidative stress markers, and endothelin 1 (ET-1) were assessed. OPN levels were significantly (P < 0.05) higher in RA (median 9.93, range 4.36-47.80 ng/mL) than in SSc (4.3, 2.1-19.7 ng/mL) or controls (5.2, 4.1-9.4 ng/mL). In RA patients, log-OPN was related to log-C-reactive protein (log-CRP) (r = 0.30, P < 0.05), age (r = 0.38, P < 0.01), Health Assessment Questionnaire (HAQ) (r = 0.58, P < 0.0001), and inversely related to total cholesterol (r = -0.33, P < 0.05) and apolipoprotein A (apoA) (r = -0.58, P < 0.001), but not to oxidative stress markers and ET-1. PWV was similar in RA (median 8.1, range 4.7-16.4 m/s) and SSc (median 8.7, range 7.1-13.1 m/s), but significantly greater (P < 0.01) than controls (median 7.5, range 4.1-10.4 m/s). Aortic PWV was related to log-OPN (r = 0.40, P < 0.01) only in RA patients. It also was related to age (r = 0.34, P < 0.05), mean blood pressure (r = 0.44, P < 0.001), and HAQ (r = 0.48, P < 0.001). In multiple regression analysis (r(2) = 0.36), including confounders, log-OPN remained a significant predictor (P < 0.05) of PWV in RA. Elevated plasma OPN levels are associated with increased arterial stiffness in RA patients, suggesting that this protein might represent a bridge protein between inflammation and the consequent joint damage and cardiovascular risk in RA patients.
Molecular Medicine 07/2009; 15(11-12):402-6. · 4.47 Impact Factor
[show abstract][hide abstract] ABSTRACT: Several studies have been carried out in order to investigate surface electromyography (SEMG) response on fibromyalgic (FM) patients. Some studies failed to demonstrate differences between FM patients and healthy individuals while others found differences in SEMG parameters. Different muscular region have been analyzed in FM patients and heterogeneity is also produced because of the different ways in which the SEMG technique is used. The aims of this study were to evaluate muscle modifications by SEMG analysis in FM women with respect to a sample of healthy controls and to investigate the relationships between SEMG parameters and the clinical aspects of the disease.
SEMG was recorded in 100 FM women (48.10 +/- 11.96 yr) and in 50 healthy women (48.60 +/- 11.18 yr), from the tibialis anterior and the distal part of vastus medialis muscle during isometric contraction. Initial values and rate of change of median spectral frequency (MDF) and conduction velocity (CV) of the SEMG signal were calculated.The clinical parameters "Fibromyalgia Impact Questionnaire", pain, tender points, tiredness were evaluated and the relationships between these data and the SEMG results were also studied. For the statistical analysis Mann-Whitney test, chi-square test and Spearman correlation were used.
MDF absolute values and the so-called Fatigue Index (FI) were significantly lower (p < 0.001) in both muscles studied in FM patients (MDF: 93.2 microV; FI: 1.10, 0.89) with respect to healthy controls (MDF: 138.2 microV; FI: 2.41, 1.66) and a smaller reduction in the percentage values of MDF was observed in FM patients vs controls (22% vs 38%). A significant correlation was found between the SEMG parameter decrement of normalized median frequency (MNF) (%) and seriousness of FM (evaluated by means of tender points).
We have found some interesting muscle modifications in FM patients with respect to healthy controls, regarding MDF, CV and FI values which resulted significantly lower in FM. Patients might have a different fiber recruitment or a possible atrophy of type II fibers suggesting that they are not able to reach muscle relaxation.
[show abstract][hide abstract] ABSTRACT: To evaluate plasma amino acid (AA) concentrations in patients affected by fibromyalgia (FM) and to study the relationships between their levels and FM clinical parameters.
20 AAs were assessed in 34 FM patients and in 18 healthy volunteers by means of a modified version of the Waters picotag method.
Significant lower plasma taurine, alanine, tyrosine (Tyr), valine, methionine, phenylalanine and threonine concentrations, and the sum of essential AAs were observed in FM patients vs healthy controls (P<0.05). Tyr CAA' ratio and the sum of AAs competing with tryptophan for brain uptake were significantly reduced in FM (P<0.05). A significant correlation was found between FM clinical parameters and certain AAs.
Our results suggest probable defects of gut malabsorption of certain AAs in FM patients. Moreover, given the reduced Tyr CAA' ratio in FM patients, a possible impairment of the cathecolaminergic system in the FM syndrome may be suggested.
[show abstract][hide abstract] ABSTRACT: To evaluate the intracellular levels of the high energy adenosine triphosphate nucleotide ATP and essential divalent cations, calcium and magnesium, in platelets of patients affected by primary fibromyalgia syndrome (FMs).
Platelet ATP and cation concentrations were measured in 25 patients affected by FMs and 25 healthy volunteers through a chemiluminescent and a fluorimetric assay, respectively.
Significant lower ATP levels were observed inside platelets of FM patients (fmol ATP/plt: 0.0169+/-0.0012 vs. healthy controls, fmol ATP/plt: 0.0306+/-0.0023, mean+/-SEM) (*** P<0.0001). A trend towards higher calcium concentrations (P=0.06) together with significant increased magnesium levels were also reported in platelets of patients by comparison with controls (P=0.02).
This preliminary study suggests that disturbances in the homeostasis of platelet ATP metabolism-signaling and calcium-magnesium flows might have a relevance in the pathogenesis of FMs.
[show abstract][hide abstract] ABSTRACT: We report on a female case of rheumatoid arthritis (RA) with hepatitis C virus comorbidity. The patient was treated once weekly over ten consecutive weeks with Adacolumn device. Clinical assessment and HCV-RNA concentration were monitored at weeks-1, 4, 9, 14 and during follow-up over 6 months. At the end of the treatment: the number of tender and swollen joints, patient's global assessment of disease activity (VAS), physician's VAS, C-reactive protein (CRP) decreased, respectively; ACR response was >20. This improvement was maintained for over 2 months. At week 38, the patient was re-treated achieving again an ACR response >20.
Rheumatology International 01/2008; 28(3):295-7. · 2.21 Impact Factor
[show abstract][hide abstract] ABSTRACT: Our objectives were to investigate thyroid abnormalities and autoimmunity in 120 patients affected by fibromyalgia (FM) and to study their relationships with clinical data and symptoms. Thyroid assessment by means of antithyroglobulin antibodies, antithyroid peroxidase antibodies, free triiodo-thyronine, free thyroxine, and thyroid stimulating hormone analyses was carried out. The clinical parameters "Fibromyalgia Impact Questionnaire", pain, tender points, fatigue, and other symptoms, and the presence of depression or anxiety disorders were evaluated. The basal thyroid hormone levels of FM patients were in the normal range, while 41% of the patients had at least one thyroid antibody. Patients with thyroid autoimmunity showed a higher percentage of dry eyes, burning, or pain with urination, allodynia, blurred vision, and sore throat. Correlations found between thyroid autoimmunity and age or with the presence of depression or anxiety disorders were not significant. However, in the cohort of post-menopausal patients, the frequency of thyroid autoimmunity was higher with respect to pre-menopausal patients. In conclusion, autoimmune thyroiditis is present in an elevated percentage of FM patients, and it has been associated with the presence of typical symptoms of the disease.
[show abstract][hide abstract] ABSTRACT: The objectives of the present study were to evaluate the presence of antipolymer antibody (APA) seropositivity in 285 Italian patients affected by primary fibromyalgia (FM) and to verify whether APA levels correlate with disease severity and with cytokine levels.APA levels were determined on serum samples by an indirect ELISA kit that detects IgG APA. Cytokines (IL-1, IL-6, IL-8, IL-10 and TNFalpha) were measured by ELISA in plasma. The impact of FM on the quality of life was estimated using the Fibromyalgia Impact Questionnaire, while pain severity was evaluated using a visual analogic scale. Patients were also characterized by the presence of tiredness, stiffness, nonrestorative sleep, anxiety, depression, tension headache, irritable bowel syndrome, temporomandibular dysfunction and Raynaud's phenomena. Using a cut-off value of 30 U, APA-positive values were detected in 60 FM patients (21.05%) and in 15 healthy control individuals (15.00%) without significant differences among their levels or the percentage of seropositivity. FM patients with moderate and severe symptoms had slightly higher APA levels with respect to patients with mild symptoms. APA-seropositive patients exhibited significant correlations between APA levels and the Fibromyalgia Impact Questionnaire estimate (P = 0.042), tiredness (P = 0.003) and IL-1 levels (P = 0.0072). In conclusion, APA cannot be considered a marker of disease in Italian FM patients. The presence of APA, however, might permit the identification of a subset of FM patients with more severe symptoms and of patients who may respond differently to different therapeutic strategies.
Arthritis research & therapy 02/2007; 9(5):R86. · 4.27 Impact Factor
[show abstract][hide abstract] ABSTRACT: To examine the possible role of the soluble factor in fibromyalgia (FM) by studying the correlation of cytokine levels with the patients' clinical and psychiatric profile.
Eighty FM patients underwent clinical and psychiatric evaluations, and plasma levels of cytokines (IL-1, IL-6, IL-8, IL-10, TNF-alpha), aspecific markers of inflammation, rheumatoid factor (RF), anti-extractable nuclear antigen (ENA) antibodies, and anti-nuclear factor (FAN) were measured.
Higher levels of IL-10, IL-8 and TNF-alpha were found in FM patients than in controls. Significant correlations between the biochemical parameters and clinical data were found.
The higher levels of cytokines found in FM patients suggest the presence of an inflammatory response system (IRS) and highlight a parallel between the clinical symptoms and biochemical data. They support the hypothesis that cytokines may play a role in the clinical features of fibromyalgia. In addition, the similar cytokine patterns found in FM patients with different psychiatric profiles suggests that IRS impairment may play a specific role in the disease.
Clinical and experimental rheumatology 01/2007; 25(2):225-30. · 2.66 Impact Factor
[show abstract][hide abstract] ABSTRACT: The aim of the study was to evaluate the kinetic parameters of a specific serotonin transporter (SERT) and serotonin uptake in a mentally healthy subset of patients with fibromyalgia. Platelets were obtained from 40 patients and 38 healthy controls. SERT expression and functionality were evaluated through the measurement of [3H]paroxetine binding and the [3H]serotonin uptake itself. The values of maximal membrane binding capacity (Bmax) were statistically lower in the patients than in the healthy volunteers, whereas the dissociation constant (Kd) did not show any statistically significant variations. Moreover, a decrease in the maximal uptake rate of SERT (Vmax) was demonstrated in the platelets of patients, whereas the Michaelis constant (Km) did not show any statistically significant variations. Symptom severity score (tiredness, tender points index and Fibromyalgia Impact Questionnaire) were negatively correlated with Bmax and with Vmax, and positively correlated with Km. A change in SERT seems to occur in fibromyalgic patients, and it seems to be related to the severity of fibromyalgic symptoms.
Arthritis research & therapy 02/2006; 8(4):R99. · 4.27 Impact Factor
[show abstract][hide abstract] ABSTRACT: We conducted the present study to investigate protein expression and functioning of A2A and A2B adenosine receptors (ARs) in neutrophils of patients affected by systemic sclerosis (SSc). The presence of A2A and A2B ARs was assessed by immunoblotting using specific antibodies. Equilibrium A2A and A2B ARs binding parameters were evaluated by radioligand binding assay. Functional studies were conducted to investigate coupling of the A2B AR to the adenylyl cyclase pathway. This is the first report of the use of Western blot analysis to confirm the presence of A2A and A2B ARs in human neutrophils. No significant changes in A2A AR binding parameters or expression levels were detected between SSc patients and healthy control individuals. A significant decrease (65%) in the maximum density of A2B AR binding sites occurred in SSc neutrophils, whereas no changes in the affinity constant values were found. Moreover, a decrease in A2B AR mediated adenylyl cyclase activity was observed in patients with SSc. Our findings demonstrate the occurrence of selective alterations in A2B AR density and signalling in SSc.
Arthritis research & therapy 02/2005; 7(2):R189-95. · 4.27 Impact Factor