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Biomedical subjects

S Zeminian

Publications and source records attributed to S Zeminian.

17 recordsLinked to original sources

Expression of plasminogen activator inhibitor-1 in human adipose tissue: a role for TNF-alpha?

Elevated plasminogen activator inhibitor-1 (PAI-1) plasma levels, responsible for reduced fibrinolysis, are associated with animal and human obesity and with increased cardiovascular disease. The expression of PAI-1 has been found recently in animal and human adipose tissue. Factors and mechanisms regulating such an expression remain to be elucidated. In omental and/or subcutaneous biopsies from obese non-diabetic patients, incubated in Medium 199, we have confirmed that human adipose tissue expresses PAI-1 protein and mRNA; furthermore we have demonstrated that such an expression is clearly evident also in collagenase isolated human adipocytes and that it is stimulated by incubation itself and enhanced by exogenous human tumor necrosis factor-alpha (h-TNF-alpha). Since human adipose tissue produces TNF-alpha, to further characterize the relationship of PAI-1 to TNF-alpha, human fat biopsies were also incubated with Pentoxifylline (PTX) or Genistein, both known to inhibit endogenous TNF-alpha through different mechanisms. PTX caused a dose-dependent decrease of basal PAI-1 protein release, reaching 80% maximal inhibitory effect at 10(-3)M, the same inhibitory effect caused by Genistein at 100 microg/ml. This was associated to a marked inhibition of PAI-1 mRNA and of endogenous TNF-alpha production. Furthermore, when human fat biopsies were incubated in the presence of polyclonal rabbit neutralizing anti-human TNF-alpha antibody (at a concentration able to inhibit 100 UI/ml human TNF-alpha activity), a modest but significant decrease of the incubation induced expression of PAI-1 mRNA was observed (19.8+/-19.0% decrease, P = 0.04, n = 7). In conclusion, the results of this study demonstrate that PAI-I expression is present in human isolated adipocytes and that it is enhanced in human adipose tissue in vitro by exogenous TNF-alpha. Furthermore our data support the possibility of a main role of endogenous TNF-alpha on human adipose tissue PAI-1 expression. This cytokine, produced by human adipose tissue and causing insulin resistance, may be a link in the clinical relationship between insulin-resistance syndrome and increased PAI-1 plasma levels.

Adipose Tissue↗

[Combined drug therapy in recent-onset rheumatoid arthritis. Evaluation after 1 year of treatment].

The aim of our study is to evaluate the efficacy and safety of a combination therapy with hydroxycloroquine, gold sodium thiomalate and methotrexate in patients affected by recent onset active rheumatoid arthritis. Twenty-five patients (6 men e 19 women, average age 46.2 +/- 12.2) were enrolled in this study and 18 of them have been treated for 1 year with the three above-mentioned drugs at optimal doses. Drug toxicity was carefully monitored. Clinical and hematochemical parameters of efficacy were evaluated every three months. Radiographic joint study was performed at the beginning and at the end of the study. Seven patients dropped out, six of them for side effects, due to hydroxycloroquine in 1 case and to gold sodium thiomalate in 5 cases; 1 patient withdrew his consent. No life-threatening or irreversible adverse reactions were observed. The eighteen patients who completed the one year trial presented a remarkable improvement of clinical and hematochemical parameters. In only 1 case one erosion appeared at the end of the study. In conclusion, the combination therapy with hydroxycloroquine, gold sodium thiomalate and methotrexate seems to be effective and burdened by an acceptable level of toxicity.

Adult↗

Iloprost as cyclic five-day infusions in the treatment of scleroderma. An open pilot study in 20 patients treated for one year.

OBJECTIVE: To evaluate the safety and efficacy of cyclic intravenous iloprost therapy in diffuse or limited scleroderma. METHODS: Twenty patients, 14 women and 6 men with a mean age of 47.8 +/- 8.2 years, were given iloprost infusions for six hours a day during five consecutive days, at a rate of 0.5 to 2 ng/kg/min. The course was repeated every three months for one year. Efficacy was evaluated based on a scleroderma skin lesion score, an ischemic lesion score, a well-being self-assessment score, and lung function tests including measurement of the diffusing capacity of the lung for carbon monoxide. Safety was assessed based on adverse event collection. RESULTS: The scleroderma skin lesion and ischemic lesion scores decreased significantly over the one-year treatment period, from 37.1 +/- 16.5 to 10.2 +/- 6.9 (P < 0.001) and from 31.8 +/- 19.1 to 2.2 +/- 2.0 (P < 0.05), respectively. The well-being self-assessment score also showed a significant improvement, from 71.4 +/- 16.5 to 15.0 +/- 6.6 (P < 0.001). The diffusing capacity for carbon monoxide was decreased in 11 patients at baseline and showed a slight, non significant increase in these patients after the treatment period. No serious or persistent side effects were recorded. CONCLUSION: Cyclic intravenous iloprost therapy was associated with improvements in skin changes and in general health, as well as with a slight increase in the diffusing capacity of the lung for carbon monoxide. Our data suggest that iloprost may act on some of the pathogenetic mechanisms of scleroderma in a way that improves the course of the disease.

Female↗

Sjögren's syndrome associated with autoimmune hepatitis. A case report.

Liver involvement in patients with primary Sjögren's syndrome is rare, usually without clinical significance and histologically characterized by a feature like stage 1 primary biliary cirrhosis. We describe herein a case of acute and severe autoimmune hepatitis in a patient suffering from primary Sjögren's syndrome. The diagnosis of Sjögren's syndrome was performed in 1989. In June 1995 the patient presented severe weakness, jaundice and elevation of transaminases; moreover IgG raised to 5560 mg/dl and ANA titre increased to 1:20480. The patient denied alcohol and drug use and a viral hepatitis was excluded. Antimitochondrial antibodies, anti-smooth muscle antibodies and antibodies against liver kidney microsomes were negative. An abdomen ultrasound examination revealed hepatomegaly, with irregular echogenic structure and lymphoadenomegaly near the celiac tripod. Liver biopsy demonstrated a picture of autoimmune hepatitis. The patient was treated with prednisone 50 mg/day and azathioprine 50 mg/day, with improvement in clinical and liver function indices. At present, the patient is given only 10 mg/day of prednisone. The association of Sjögren's syndrome with autoimmune hepatitis is very rare: in the literature only one other similar case has been reported.

Autoimmune Diseases↗

Changes of neutrophil migration without modification of in vitro metabolism and adhesion in Behçet's disease.

OBJECTIVE: Increase of neutrophil chemotaxis in Behçet's disease (BD) has been described, but it is not clear whether there is a correlation with other variables of neutrophil function and whether these modifications correlate with disease activity. METHODS: We studied neutrophil functions in patients with BD in the acute phase in comparison with healthy control subjects and with the same patients during disease remission, with or without therapy. We investigated in vivo neutrophil migration by Senn's skin window technique and measured adhesion assay and superoxide production in circulating and migrating neutrophils after different stimuli. RESULTS: Neutrophil migration in vivo was 101.3 +/- 17.9 x 10(6) polymorphonuclear lymphocytes (PMN)/cm2/24 h in patients with BD in the acute phase and 66.1 +/- 7.8 x 10(6) PMN/cm2/24 h in controls (p < 0.001). No correlation was found between leukocyte counts and neutrophil migration. Neutrophil migration evaluated in the same patients in a phase of disease remission was 58.3 +/- 10.3 x 10(6) PMN/cm2/24 h (p < 0.001 vs acute phase, not significant vs controls). The neutrophils of the exudate were normally primed to response to the chemotactic peptide fMLP. No differences between the 2 groups were found in superoxide production, adhesion under basal conditions, or in response to different stimuli by circulating and migrating neutrophils. CONCLUSION: Abnormally high migration of neutrophils in the active phase of BD is the only consistent neutrophil dysfunction. Since this modification is reversed by therapy, the evaluation of in vivo neutrophil migration may be useful in diagnosing and monitoring disease activity. Blood neutrophils have normal responses to different stimuli, indicating they are not primed by the disease state.

Adult↗

Sjögren's syndrome with anticentromere antibodies.

Clinical and laboratory findings in 10 women with Sjogren's syndrome and positive anticentromere antibodies were compared to those in 50 patients with Sjögren's syndrome and typical serologic features. The anticentromere antibody-positive patients were more likely to have Raynaud's phenomenon and less likely to have leukopenia polyclonal hypergammaglobulinemia, rheumatoid factor, and anti-SSA/Ro antibody. Four anticentromere antibody-positive patients developed limited cutaneous scleroderma during follow-up, but none had lymphoma; some of the other patients in this group exhibited stable symptoms typical for Sjögren's syndrome. Among our overall population of Sjogren's syndrome patients who met diagnostic criteria for primary Sjogren's syndrome at the first evaluation, 16.6% tested positive for anticentromere antibodies.

Adult↗

Finger skin temperature in patients affected by Raynaud's phenomenon with or without anticentromere antibody positivity.

We evaluated finger skin temperature in 36 patients affected by Raynaud's phenomenon with or without anticentromere antibody positivity. The temperature measured under basal conditions and after dipping the finger in water at 10 degrees C for 5 min was similar in both groups; the temperature at the end of an 18-min recovery period was significantly lower in anticentromere antibody positive patients. This observation suggests a persistent digital vasospasm after the cold test in patients suffering from Raynaud's phenomenon with anticentromere antibody positivity. This autoantibody seems to identify a subgroup of patients affected by Raynaud's phenomenon with a severe involvement of the microcirculation.

Adult↗

Neutrophil migration, oxidative metabolism, and adhesion in elderly and young subjects.

OBJECTIVE: To evaluate neutrophil functions in the elderly. METHODS: We investigated the PMN migration in vivo and PMN superoxide production and adhesion in response to a variety of compounds; PMN have been isolated both from blood and from a skin experimental exudate (obtained by Senn's skin window technique) of 25 normal elderly and of 25 normal young control subjects. RESULTS: No difference was found in PMN migration in vivo (62.9 +/- 21.3 x 10(6) and 65.5 +/- 9.1 x 10(6) PMN/cm2/24 hours in elderly and young subjects respectively), neither were different the adhesion under basal condition and after some stimuli and the superoxide production in basal condition and in response to STZ and PMA in two groups. In elderly subjects superoxide production, in response to fMLP, markedly resulted lower than in young controls both by circulating PMNs (3.6 +/- 2.7 and 9.3 +/- 3.3 nMOLES O2-/10(6) PMN respectively, p < 0.0001) and by exudate PMNs (13.6 +/- 4.3 and 19.4 +/- 6 nMOLES O2-/10(6) PMNs respectively, p < 0.005). CONCLUSION: Many PMN functions in the elderly do not differ from young people, suggesting that the overall defense function of these cells is not affected by aging. The only parameter that we have found to be different between the two groups is the poor superoxide production after fMLP stimulus of PMNs. The stimulus- and function-specificity of this defect in PMNs from elderly subjects indicates the existence of a dysregulation of the signal transduction pathway distal to fMLP receptor and proximal to NADPH oxidase activation.

Adult↗

A case of parvovirus-B19 adult acute arthritis with some allergic disease clinical features.

A 31-year old woman suddenly presented arthralgias at wrists, knees and feet, swelling of eyelids and the upper lip, itching behind the ears, fever and macular rash on the extensory surface of legs, face and back. Signs and symptoms were strongly suggestive of an allergic reaction but human Parvovirus-B19 serology was positive, IgE serum levels were normal, skin prick tests and RAST for aliments were negative. Joint symptoms and swelling diminished in about four weeks. The relationship between the clinical manifestation of Parvovirus-B19 infection and features of allergic diseases is discussed.

Acute Disease↗

Parvovirus B19 infection and rheumatic diseases.

We reviewed the literature on relationships between human parvovirus B19 infection and rheumatic diseases. Parvovirus B19 causes erythema infectiosum in childhood, transient anemia in immunocompetent individuals, and potentially severe infections in fetuses; laboratory evidence that the virus is directly responsible for these disorders has been obtained. Acute arthropathy meeting American College of Rheumatology criteria for rheumatoid arthritis and disorders meeting some of the classification criteria for systemic lupus erythematosus are the most striking rheumatic manifestations of parvovirus B19 infection. Purpuric lesions have also been reported. Parvovirus B19 infection may be capable of inducing a number of manifestations that have not yet been described in the literature. Although the relationship between human parvovirus B19 infection and rheumatic diseases has been the focus of many studies, compelling evidence that the virus is directly involved in the pathogenesis of rheumatic diseases has not yet been obtained.

Humans↗

Lack of association of T cell receptor V beta 8 polymorphism with rheumatoid arthritis in United Kingdom and Italian white patients.

OBJECTIVES: To study if the reported association of a BamH I 2kb RFLP of the T cell receptor V beta 8 gene with DR4+ rheumatoid arthritis patients is found in non-American white populations. METHODS: The frequency of this RFLP in two different populations was analysed. Eighty one northern Italians were studied for HLA-DR genotypes and V beta 8 polymorphism, and 29 DR4+ British white patients were studied for V beta 8 polymorphism. RESULTS: No association between the V beta 8 RFLP and DR4 was found with rheumatoid arthritis in both groups. CONCLUSION: The reported V beta 8-DR4 association is not generally applicable. The lack of association in our populations may be due to genetic differences, or to differences in factors which shaped the T cell repertoire.

Arthritis, Rheumatoid↗

[Current views on the pathogenesis and therapy of ankylosing spondylitis].

Ankylosing spondylitis is a frequent and disabling inflammatory chronic disease, that affects mainly young men. In this paper the authors reviewed the pathogenetic mechanism and pharmacological and physical treatment. Nowadays the pathogenesis of ankylosing spondylitis is considered similar to that of reactive arthritis. The management of each patient should take into account the different aspects of the disease; therefore it should be individually designed.

Adult↗

Middle ear function in rheumatoid arthritis: a multiple frequency tympanometric study.

OBJECTIVE: To evaluate the modifications in the mechanical properties of the middle ear in rheumatoid arthritis by assessing its resonance frequency. METHODS: Thirty patients with rheumatoid arthritis (RA) aged 20 to 68 years (mean age 45.8 +/- 12.4 yrs) were investigated by multiple frequency tympanometry and their data were compared with those obtained in a control group of 48 subjects aged from 19 to 65 years. RESULTS: Normal values, calculated at the 95th percentile from the control group, ranged from 800 to 1250 Hz. Eleven RA patients (36.6%) displayed abnormal resonance values. These findings were monolateral in 9 patients and bilateral in 2 (in all a total of 13 ears). Nine out of 13 ears with abnormal multiple frequency tympanometry data were characterized by an increase in resonance and 4 by a decrease. CONCLUSION: These findings were attributed to abnormal acoustic impedence of the middle ear and indicate a possible involvement of the ossicular diarthroses in RA. Our study suggests that RA may involve the incudo-malleolar and incudo-stapedial joints, altering the ossicular mechanisms in response to static air pressure modifications.

Acoustic Impedance Tests↗