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Biomedical subjects

A Sulli

Publications and source records attributed to A Sulli.

At least 37 records · Page 2Linked to original sources
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↗
PubMed2002

Brain functional involvement by perfusion SPECT in systemic sclerosis and Behçet's disease.

Involvement of the central nervous system is frequent in systemic immune-mediated diseases, such as systemic lupus erythematosus, Behçet's disease (BD), and systemic sclerosis (SSc). Structural brain examinations, such as computed tomography and magnetic resonance imaging, may be useful in diagnosing and following-up these cerebral syndromes in some cases, but they are more often inconclusive. Single photon emission computed tomography (SPECT) with perfusion tracers is a powerful method that can disclose brain involvement in many clinical situations, even in patients with subtle neurological symptoms. In fact, perfusion tracers can disclose regional hypoperfusion caused by both ischemia due to vascular narrowing and neuronal metabolic derangement due to direct neuronal damage. The latter phenomenon occurs because the blood flow to the brain is strictly regulated by metabolic demands, so that hypometabolism is reflected by hypoperfusion in most instances. SPECT findings in 42 mainly neurologically asymptomatic patients with SSc and in eight mainly neurologically symptomatic patients with BD are reported. SPECT was shown to be very sensitive and disclosed brain functional deficits in approximately half of SSc patients without neurological complaints and in all patients with BD, who had various neurological symptoms but usually inconclusive structural brain examinations.

Aged↗
PubMed2002

Carotid atherosclerosis in patients with rheumatoid arthritis: a preliminary case-control study.

A preliminary study was undertaken to investigate the severity of atherosclerotic lesions of neck arteries in patients with rheumatoid arthritis (RA) in comparison with matched controls. The working hypothesis derives from the recent view that the atherosclerotic plaque is essentially an inflammatory lesion. Thus, patients affected by a chronic inflammatory disease, such as RA, might show acceleration of atherosclerosis despite treatment with anti-inflammatory drugs. In 19 patients with RA the prevalence of atherosclerosis of internal carotid arteries, as seen on high-resolution duplex-scanning of neck arteries, was significantly (p < 0.05) higher than in 19 controls, whereas no significant difference was found for the other arteries. Factors underlying this finding are not known; increased levels of homocysteine and other thiol compounds that may enhance atherosclerosis in RA patients deserve further investigation. Moreover, more specific factors of RA are currently being investigated. In fact, immune complexes fixing C1q bind to endothelial receptors, thus triggering an upregulation of adhesion molecules, such as E-selectin and intercellular and vascular cell adhesion molecules 1, on the endothelium surface.

Aged↗
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

No evidence of an association between Helicobacter pylori infection and Raynaud phenomenon.

BACKGROUND: Raynaud phenomenon (RP) is a vasospastic condition that manifests itself as cold-induced ischemic attacks of the fingers with skin color changes. It may be classified as primary (PRP) or secondary (SRP), if associated to other diseases, mainly connective-tissue diseases. Recently, the association between PRP and Helicobacter pylori infection has been reported. The aims of this study were to evaluate the prevalence of gastric H. pylori infection in a large group of patients affected by PRP and SRP and to assess whether it was more evident in patients with more recent onset of RP. METHODS: Ninety-eight consecutive patients (93 F and 5 M), referring to our videocapillaroscopic service for the diagnosis of vascular and connective-tissue diseases, were evaluated. Forty-nine of them were affected by PRP and 49 by SRP. Patients were classified as having PRP on the basis of normal serological and immunological findings, normal videocapillaroscopic examination and exclusion of other conditions inducing RP. H. pylori infection was diagnosed by 13C-urea breath test (UBT). Two groups of 49 age-and sex-matched controls, respectively, were also evaluated. RESULTS: Patients with SRP resulted significantly older than those with PRP (P < 0.006). UBT was found positive in 22/49 patients with PRP (45%) and in 29/49 patients with SRP (59%). The positivity of the respective control groups was 36% and 53% (P = NS). There was no higher prevalence of H. pylori infection in patients with RP lasting for less than 4 years. CONCLUSIONS: The results do not confirm the previously reported high prevalence of H. pylori infection in patients with PRP. A high association was not even found between the presence of the microorganism and SRP. There was no difference in the prevalence of H. pylori infection among the subgroups with more recent onset of both PRP and SRP.

Adult↗
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

Validation of an Italian version of the arthritis impact measurement scales 2 (ITALIAN-AIMS2) for patients with osteoarthritis of the knee. Gonarthrosis and Quality of Life Assessment (GOQOLA) Study Group.

OBJECTIVE: To validate a translated version of the revised and expanded Arthritis Impact Measurement Scales (AIMS2) to be used by Italian patients with osteoarthritis (OA) of the knee. METHODS: The AIMS2 was translated into Italian and administered to a cohort of 178 outpatients with symptomatic OA of the knee who attended 12 participating rheumatological institutes in northern, central and southern Italy. A random sample of 71 patients were readministered the AIMS2, 7 days after the first visit, to evaluate the instrument's test-retest reliability. After 6 months, the subjects were asked to return to the institutes for a second administration of the questionnaire. RESULTS: The internal consistency reliability of each scale score, as estimated by Cronbach's alpha coefficient, was high and indicated that the components of the scale measured the same construct. The items all correlated with each other, but there was no redundancy; this indicates that each domain addressed a somewhat different aspect of functional disability. The test-retest reliability equalled or exceeded 0.80 for eight of the 12 scales. Factor analysis provided a three-factor health status model explaining 63.5% of the variance. Arthritis pain and psychological scale were loaded on the first factor, together with physical scales for mobility level and walking and bending. The upper limb function scales formed the second factor. The third factor was determined by the social dimension. These results demonstrate that the physical health status scales of the AIMS2 are valid, as shown by the significant, moderate to high correlations between the AIMS2 subscales and the majority of the clinical measures. CONCLUSION: Our data suggest that, like the original questionnaire, the translated version of AIMS2 is a reliable, consistent and valid instrument for measuring health status and physical functioning in patients with OA of the knee.

Aged↗
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

Nailfold videocapillaroscopy assessment of microvascular damage in systemic sclerosis.

OBJECTIVE: To correlate microvascular abnormalities, evaluated by nailfold videocapillaroscopy (NVC), with the duration of both Raynaud's phenomenon (RP) and systemic sclerosis (SSc) from the date of diagnosis, in a large number of patients with SSc. METHODS: Ninety-seven consecutive patients were recruited and distributed into 3 groups on the basis of the morphological NVC patterns observed: "early" (E), "active" (A), and "late" (L). In each group the age of patients, age at onset, and the duration of RP as well as of overt SSc were investigated and correlated with the different NVC pattern variables. RESULTS: The early appearance of giant capillaries and hemorrhages (E pattern) is of great relevance for the early diagnosis of SSc. Therefore, these alterations are more evident in the active phase of the disease (A pattern). Conversely, the NVC observation of loss of capillaries and vascular architectural disorganization and the presence of ramified/bushy capillaries (L pattern) represents the clearest aspect of advanced SSc microvascular damage. These morphological alterations were found to correlate significantly with the duration of both RP and SSc, as well as with age of patients (p = 0.0001). No significant differences were observed when the variables were analyzed in the patients classified as having limited cutaneous SSc or diffuse cutaneous SSc. CONCLUSION: Classification of defined major nailfold patterns may be useful in assessing the appearance and progression of sclerodermic microangiopathy. As well, nailfold changes might represent a morphological reproduction of the evolution of SSc.

Female↗
PubMed2000

Antiproliferative and antiinflammatory effects of methotrexate on cultured differentiating myeloid monocytic cells (THP-1) but not on synovial macrophages from patients with rheumatoid arthritis.

OBJECTIVE: We investigated the antiproliferative and antiinflammatory effects of methotrexate (MTX) on differentiating/differentiated cells, namely cultured human monocytic myeloid cells (THP-1), and primary cultures of synovial macrophages from patients with rheumatoid arthritis (RA). METHODS: We evaluated early and late apoptosis as well as natural cytokine inhibitor production, such as the interleukin 1 (IL-1) receptor antagonist (IL-1ra) and the soluble tumor necrosis factor receptor (sTNFr). RESULTS: Within THP-1 cells we observed a significant (p < 0.001) dose-dependent inhibition of proliferation (at 24-48 and 72-96 h) and a significant presence of apoptosis (at 24-48 h) with MTX concentrations of 500, 100, and 75 microg/ml compared with untreated controls. No significant changes were observed with 5 microg/ml or 500 to 50, and 5 ng/ml. A significant increase of IL-1ra (p < 0.001) was observed with MTX concentrations of 5 microg (51.43 +/- 2.53 vs 16.22 +/- 5.19 pg/ml control) and 500 ng (36.43 +/- 3.3 vs 16.22 +/- 5.19 pg/ml control) at all the tested times. No significant changes were observed for the sTNFr p75. Evaluating the RA synovial macrophages, we obtained no significant effects on cell proliferation and apoptosis with MTX treatment at 24 h and at the concentration of 50 microg/ml (achievable in the serum with low dose MTX treatment in RA). No significant changes were observed for the IL-1ra and no detectable levels for the sTNFr p75 were detected after treatment with MTX. CONCLUSION: This study shows that the antiproliferative and antiinflammatory effects of MTX on human cultured monocytes are dose-dependent. The antiproliferative activity seems to be mediated by cell apoptosis and the antiinflammatory activity seems to be related to cytokine inhibitor release.

Anti-Inflammatory Agents↗
PubMed1999

Melatonin influences interleukin-12 and nitric oxide production by primary cultures of rheumatoid synovial macrophages and THP-1 cells.

Because some of the clinical symptoms related to rheumatoid arthritis (RA) synovitis, such as joint morning stiffness and gelling, might be related to the effects exerted by the diurnal rhythmicity of the neurohormone melatonin (MLT) on synovial immune cell activation, we decided to evaluate the influence of MLT on the production of IL-12 and nitric oxide (NO) on primary cultures of RA synovial macrophages. Synovial macrophages were also prestimulated with lipopolysaccaride (LPS). Results were compared with those obtained on cultured human myeloid monocytic cells (THP-1). A significant increase in IL-12 (p = 0.01) was found in media of MLT-stimulated synovial macrophages versus RMPI-treated synovial macrophage controls. Interestingly, a significant decrease of IL-12 (p < 0.0001) was observed in media of synovial macrophages previously activated with LPS and then treated with MLT, when compared to synovial macrophages treated with LPS alone. A significant increase in NO levels (p = 0.01) was found in MLT-stimulated synovial macrophages versus RMPI-treated synovial macrophage controls. Interestingly, a nonsignificant increase of NO levels was observed in media of synovial macrophages previously activated with LPS and then treated with MLT, when compared to cynovial macrophages treated with LPS alone. Finally, a significant increase in IL-12 (p = 0.03) and NO (p = 0.002) concentrations was observed in media of MLT-stimulated THP-1 cells versus RMPI-treated controls. Our results therefore show that MLT induces IL-12 secretion and NO production by unstimulated cultured RA synovial macrophages and human monocytic myeloid THP-1 cells. The unexpected and opposite effects on IL-12 and NO production in RA synovial macrophages treated with LPS may be related to dose-dependent mechanisms exerted by MLT or to altered cell priming in RA macrophages; these are matters of our further research. This study strongly supports the role of MLT in immune response modulation and in particular suggests a close relationship between diurnal rhythmicity of neuroendocrine pathways, cytokine and reactive oxygen intermediate production by monocyte/macrophages, and synovial arthritis symptomatology, at least in RA.

Adult↗
PubMed1999

Androgenizing effects of cyclosporin A in rheumatoid arthritis.

In order to determine the influence of CsA on whole peripheral androgen metabolism, we evaluated 14 patients with RA over a period of 12 months. Patients were treated with low-dose CsA (2.5-3.5 mg/kg/day). Other drugs influencing androgen metabolism were excluded. Plasma levels of Test and of 5 alpha-androstane-3 alpha, 17 beta-diol glucuronide (Adiol-G), an important peripheral Test metabolite, were analyzed. Each patient was monthly examined for the first three months, and thereafter every three months. At each visit, the number of swollen and tender joints, as well as the visual analogic scale of pain, were evaluated. The laboratory parameters of RA activity (ESR, CRP, Hb) were also monitored, along with some safety serological indexes. Statistical analysis was performed by using nonparametrical tests. After 12 months of treatment, an evident increase in mean plasma Adiol-G concentration was observed in patients of both sexes (women's basal levels +/- SE = 2.89 +/- 0.58 ng/mL vs. 12 months = 5.71 +/- 1.33 ng/mL; men's basal levels = 4.87 +/- 0.91 vs. 9.20 +/- 0.68, respectively) (p < 0.001). The increase was already statistically significant after 4-5 weeks of treatment in male patients (p < 0.01) and after 12-14 weeks in female patients (p < 0.05). All the patients experienced the side effect of a low-degree hypertrichosis after a mean period of 4-8 weeks. Concerning clinical parameters, a significant improvement (p < 0.05) of the number of swollen and tender joints was observed after 12 months, as well as a reduction of CRP levels. No statistically significant correlation between hormonal levels and clinical or laboratory indexes of disease activity was observed. In conclusion, the appearance of a dose-related hypertrichosis and the increase in plasma androgen metabolites (Adiol-G) in CsA-treated patients should be regarded as possible markers of the influence of CsA on peripheral androgen metabolism, at the level of target cells and tissues.

Adult↗