Soluble interleukin-2-receptor and interleukin-6 changes during low-dose methotrexate treatment in rheumatoid arthritis.
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Adult↗
Biomedical subjects
A Spadaro
Publications and source records attributed to A Spadaro.
Methylprednisolone delivery by Hyalobend corneal shields and its effects on rabbit ocular inflammation.
Release of methylprednisolone from hyaluronic acid derivative corneal shields (Hyalobend), in vitro and in vivo, was evaluated as well as ocular anti-inflammatory activity in the rabbit eye. The release of methylprednisolone from Hyalobend corneal shields in vitro followed zero-order kinetics. After placing Hyalobend corneal shields in rabbit eye, aqueous and tear fluid methylprednisolone levels were detected up to 48 hours and compared with the levels obtained with methylprednisolone suspension. Hyalobend corneal shields maintained almost constant methylprednisolone levels in the rabbit tear fluid. On the contrary, the suspension gave very high tear values of steroid concentrations in the first 30 minutes but undetectable in less than 200 minutes. Hyalobend corneal shields ensured effective levels of methylprednisolone into the rabbit aqueous for up to 48 hours. Aqueous levels of drug, in the group treated with the suspension, decreased progressively and after 480 minutes were undetectable. Hyalobend corneal shields significantly reduced the conjunctival inflammation elicited by sodium arachidonate compared with control. Furthermore, Hyalobend corneal shields treatment significantly reduced the levels of PGE2 in the tear fluid. Hyalobend corneal shields increase the residence time of methylprednisolone in rabbit tear fluid and enhance the penetration into the aqueous humor as well as reduced the primary signs of ocular inflammation.
Administration, Topical↗
Synthesis, physical properties, toxicological studies and bioavailability of L-pyroglutamic and L-glutamic acid esters of paracetamol as potentially useful prodrugs.
Paracetamol ester prodrugs with L-pyroglutamic and L-glutamic acid, biosynthetic precursors of glutathione, have been synthesized to reduce paracetamol hepatotoxicity and improve bioavailability. The toxicological studies of paracetamol esters show that only L-5-oxo-pyrrolidine-2-paracetamol carboxylate reduces toxicity after administration of an overdose. The glutathione hepatic values in mice obtained by intraperitoneal injection of the ester are superimposable on controls and the oral LD50 was found to be greater than 2000 mg kg-1 and the intraperitoneal LD50 was 1900 mg kg-1. These results taken together with hydrolysis and bioavailability data show that ester is a potential candidate as a prodrug of paracetamol.
Acetaminophen↗
Interleukin-6 and soluble interleukin-2 receptor in juvenile chronic arthritis: correlations with clinical and laboratory parameters.
We sought to determine whether levels of interleukin-6 and soluble interleukin-2 receptor were correlated with clinical parameters including functional capacity indices such as Steinbrocker's class and the Juvenile Arthritis Functional Assessment Report (JAFAR) score, with tests for inflammation, and/or with immunological parameters in 24 patients with active polyarticular or pauciarticular juvenile chronic arthritis. Levels of interleukin-6 and soluble interleukin-2 receptor were significantly higher in juvenile chronic arthritis patients than in healthy controls (p < 0.005 and p < 0.00005, respectively). Interleukin-6 levels were correlated with the following parameters: number of painful joints (p < 0.025); Ritchie's index (p < 0.025); visual analog scale pain score (p < 0.025); Steinbrocker's class (p < 0.025); JAFAR score determined by patients (p < 0.05); JAFAR score determined by parents (p < 0.05); erythrocyte sedimentation rate (p < 0.0002); and serum levels of C-reactive protein (p < 0.0003), hemoglobin (p < 0.05), albumin (p < 0.025), and alpha 2-globulins (p < 0.025). Levels of soluble interleukin-2 receptor did not correlate with any of the parameters studied. Levels of interleukin-6 and soluble interleukin-2 receptor were not correlated with each other. Abnormal levels of interleukin-6 or soluble interleukin-2 receptor were not significantly associated with the presence of antinuclear antibodies, IgM-rheumatoid factor, IgA rheumatoid factor or anticardiolipin antibodies. Our findings suggest that interleukin-6 is a useful parameter for assessing juvenile chronic arthritis and that the potential clinical value of elevated levels of soluble interleukin-2 receptor in this disease needs to be further evaluated in longitudinal studies.
Adolescent↗
Correlations between peripheral and axial radiological changes in patients with psoriatic polyarthritis.
Peripheral radiological changes were investigated with respect to occurrence rates, severity and correlations with axial radiological change severity in a retrospective study in 140 patients with psoriatic polyarthritis. Study parameters were the number of erosions in joints of the hands and feet, severity of wrist lesions, sacroiliitis stage, number of syndesmophytes, number of pelvic and calcaneal enthesopathies and Larsen's damage score. Fifty patients had both peripheral changes and axial changes (bilateral stage 2 sacroiliitis or unilateral stage 3 or more sacroiliitis and/or syndesmophytes). Disease duration was correlated with radiological changes and the disease score. When patients were divided into quartiles based on polyarthritis duration, mean disease score was found to be significantly higher in the second than in the first quartile (p<0.005) and in the fourth than in the third quartile (p<0.0005), whereas the difference between the second and third quartiles was not significant. Peripheral changes progressed during the first five years of the disease. In contrast, the sacroiliitis score increased only in those patients with the longest disease durations. Correlations between severity of peripheral changes, sacroiliitis stage and disease score were found in all patients. In patients with axial lesions, peripheral involvement was more common and more severe and disease scores were significantly higher (p<0.00001). Our findings suggest that both peripheral and axial changes contribute to the severity of psoriatic polyarthritis and that the subgroup of patients with axial changes is characterized by more frequent and more severe peripheral lesions.
Adult↗
Long-term follow-up of low-dose methotrexate therapy in one case of idiopathic retroperitoneal fibrosis.
Idiopathic retroperitoneal fibrosis (RPF) is characterized by the development of a fibrotic mass surrounding the abdominal aorta and its branches, of unknown aetiology. Several immunological mechanisms can be operative in the pathogenesis of RPF. Based on this assumption we treated a patient affected by idiopathic RPF with low-dose methotrexate (MTX) therapy. To our knowledge this is the first example of the effectiveness and safety of a long-term low-dose MTX treatment in the post-surgical management of RPF.
Adult↗
Differential effects of modified beta-cyclodextrins on pharmacological activity and bioavailability of 4-biphenylacetic acid in rats after oral administration.
Gastric tolerability, absorption and pharmacological activity of the non-steroidal anti-inflammatory drug 4-biphenylacetic acid (BPAA), as an inclusion complex with beta-cyclodextrin (beta-CyD) or chemically modified beta-CyDs: 2,6-di-O-methyl-beta-CyD (DM-beta-CyD), 2,3,6-tri-O-methyl-beta-CyD (TM-beta-CyD) and 2-hydroxypropyl-beta-CyD (HP-beta-CyD), were investigated in the rat after oral administration. BPAA absorption, determined from area under the plasma concentration-time curve (AUC), was increased by complexation with all beta-CyDs in the following order: DM-beta-CyD > TM-beta-CyD > HP-beta-CyD > beta-CyD. The carrageenan paw oedema test demonstrated a significant increase in anti-inflammatory activity of BPAA and the ED50 values, compared with BPAA alone, were reduced to about a third for the BPAA-DM-beta-CyD complex and halved for the others. BPAA complexed with DM-beta-CyD, HP-beta-CyD or beta-CyD showed better gastric tolerability compared with uncomplexed drug, whereas the BPAA-TM-beta-CyD complex produced marked gastric lesions similar in extent to BPAA alone. TM-beta-CyD (500 mg kg-1) and DM-beta-CyD (1000 mg kg-1) caused gastric erosions 21 h after oral administration. The pharmacokinetic profiles of BPAA-beta-CyD complexes have shown that DM-beta-CyD is the most effective in enhancing the bioavailability of BPAA.
Absorption↗
Effect of sodium naproxen on inflammatory response induced by anterior chamber paracentesis in the rabbit.
This study evaluated the effect of sodium naproxen (a reversible competitive inhibitor of cyclo-oxygenase) and phenylephrine (a mydriatic alpha-adrenergic agent) eye drops in maintaining atropine mydriasis in the rabbit after paracentesis. Moreover, to assess the influence of these treatments on vascular and cellular inflammatory responses in the rabbit eye, several biochemical parameters were considered. Anterior chamber paracentesis significantly reduced atropine-induced mydriasis and a parallel elevation of proteins, polymorphonuclear leucocytes (PMNs), prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) levels in the secondary aqueous humour (obtained 120 min later) was observed. A significant increase in PMNs in the aqueous humour and a parallel increase in myeloperoxidase activity, a measure of PMN infiltration, in the iris-ciliary body were detected. Atropine-induced mydriasis was maintained in rabbits treated with either sodium naproxen or phenylephrine eye drops. However, only in the former group were the inflammatory parameters significantly reduced, with the exception of aqueous LTB4 levels. The inhibition of the protein influx in the aqueous humour and of the miosis produced by sodium naproxen can be related to the high drug levels in the aqueous humour that were effective in inhibiting the cyclo-oxygenase pathway of arachidonic acid metabolism, whereas the effects on PMN infiltration appear to be independent of significant release of the potent chemotactic agent LTB4, synthesized via the 5-lipoxygenase pathway.
Analysis of Variance↗
Intracellular accumulation of ofloxacin-loaded liposomes in human synovial fibroblasts.
In order to incorporate ofloxacin within liposomes, the reverse-phase evaporation technique was carried out. The liposome lipid matrix consisted of dipalmitoylphosphatidylcholine-cholesterol-dihexadecylphosphate (4: 3:4 molar ratio). The liposome formulation presented a mean size of 185 +/- 31 nm and had an encapsulation capacity of 5.3 microliters/mumol. The liposome formulation was able to deliver ofloxacin into McCoy cells in a greater amount (2.6-fold) than the free drug, improving antibiotic accumulation.
Cells, Cultured↗
Focal lymphocytic aggregates in chronic hepatitis C: occurrence, immunohistochemical characterization, and relation to markers of autoimmunity.
Intrahepatic lymphocytic aggregates are observed in chronic hepatitis C as well as in autoimmune chronic hepatitis. Autoantibodies and autoimmune manifestations may occur in hepatitis C. It has been suggested that the lymphocytic aggregates play a role in the liver injury of chronic hepatitis C by an immune-mediated mechanism. We studied the occurrence of intrahepatic lymphocytic aggregates and of autoantibodies in a consecutive series of 128 patients with chronic hepatitis C. For the phenotypic characterization of the lymphocytic aggregates cryostat sections and microwaved paraffin embedded sections were immunostained with monoclonal antibodies directed against T cell subsets, B cells, killer/natural killer cells, follicular dendritic cells, and macrophages. Autoantibodies were tested by immunofluorescence (antinuclear, anti-smooth muscle, antimitochondrial) and by enzyme-linked immunosorbent assay (anti-soluble liver antigen, anti-liver/kidney microsome, anti-human receptor for asialoglycoprotein). Focal lymphocytic aggregates in portal tracts were observed in 76 of 128 (59%) patients. The cellular composition of the aggregates was constant: a core of B cells mixed with many T helper/inducer lymphocytes, and an outer ring was prominently formed by T suppressor/cytotoxic lymphocytes. A germinal center was rarely identifiable. The presence of lymphocytic aggregates was inversely correlated with the degree of fibrosis. Lymphocytic aggregates appeared more frequently in chronic persistent and chronic active hepatitis in comparison with cirrhosis and in the presence of bile duct damage. No correlation was found between lymphocytic aggregates and autoantibodies or other markers of autoimmunity. The lymphocytic aggregates are frequent in chronic hepatitis C. Their cellular composition is similar to that of primary lymphoid follicles in lymph nodes. Their presence does not seem to be correlated with features of autoimmunity.
Adult↗
Lupus erythematosus panniculitis: an immunohistochemical study.
An immunohistochemical study on a case of lupus erythematosus panniculitis (LEP), without discoid lupus erythematosus (DLE) or systemic lupus erythematosus (SLE) signs, showed that the cells in skin infiltrates were immunologically committed lymphocytes (OKT4, OKT8, OKT11 and HLA-DR positive cells) and elements of the monocyte-macrophage lineage (Leu M3 and Leu M5 positive). No immunophenotypically identifiable B-lymphocytes were seen. Immunofluorescent IgG, IgM, C3 and C4 deposits were found in blood vessel walls of the deep dermis. These findings, similar to that described in the skin changes of SLE and DLE, suggest that immunological mechanisms are operative in localized LEP, where the dermal lesions are the only expression of the disease.
Disease Progression↗
[Value of cytological analysis of the synovial fluid in multicentric reticulohistiocytosis. A case].
The authors report the case of a patient who had both multicentric reticulohistiocytosis--a systemic disease characterized by symmetric polyarthritis and papulonodular skin lesions--and an ovarian adenocarcinoma. Synovial fluid analysis found histiocytes with a ground-glass cytoplasm, binucleate giant cells, and undifferentiated cells undergoing mitosis. PAS-positive, diastase-resistant cells similar to the synovial fluid histiocytes were seen in the synovial and cutaneous biopsy specimens. These findings established the diagnosis of multicentric reticulohistiocytosis and suggested an underlying malignancy. Whether or not multicentric reticulohistiocytosis is a paraneoplastic syndrome remains unsettled. However, our report provides evidence that synovial fluid analysis can be helpful not only for the early diagnosis of multicentric reticulohistiocytosis but also for suggesting the presence of an underlying tumor, especially when arthritis is the presenting symptom.
Adenocarcinoma↗
Rheumatoid nodules and cyclosporin A treatment.
The authors describe the appearance of rheumatoid nodules during cyclosporin A (CsA) therapy for RA. Their course was evaluated by sonography that revealed an increase in number and size of rheumatoid nodules. The relationship between CsA treatment and the onset of nodulosis is not clear and further studies are needed to assess the role of CsA treatment in the extra-articular manifestations of rheumatoid arthritis such as rheumatoid nodules.
Arthritis, Rheumatoid↗
Short-term "cyclosporin A" therapy for psoriatic arthritis.
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Adult↗
One year treatment with low dose methotrexate in rheumatoid arthritis: effect on class specific rheumatoid factors.
We evaluated the effect of a one-year treatment of low dose methotrexate (MTX) on class specific rheumatoid factors in 27 patients with rheumatoid arthritis (RA). Enzyme-linked immunosorbent assay (ELISA) showed after 6 and 12 months a significant reduction of IgM-RF, IgA-RF and IgG-RF levels from the baseline values. During MTX treatment, changes of each RF isotype were not correlated with any other isotype and its corresponding immunoglobulin changes. Moreover, immunological changes were not related to the improvement of clinical parameters. Our results showed that low dose MTX can specifically affect levels of RF isotypes, which are involved in the immune pathogenesis of RA.
Adult↗
Effects of Mipragoside on ocular allergic inflammation in the rabbit.
We evaluated the pharmacodynamic and pharmacokinetic profile of Mipragoside, a monosialoganglioside isopropyl-ester (as 0.5% w/w ophthalmic gel), on allergic inflammation of the eye induced by reverse passive Arthus reaction, on a non-immune mast cell degranulation elicited by compound 48/80 and on ocular inflammation produced by horse serum. Conjunctiva was sensitized by injection of rabbit antisera to bovine proteins and the allergic conjunctivitis was triggered by intravenous administration of bovine gamma globulin. The permeability of the blood-conjunctival barrier was evaluated by a fluorometric method. Compound 48/80 was topically administered at concentration of 50mg/ml and histological analysis of conjunctiva was performed. Horse serum was administered by intravenous injection at different days. The pharmacokinetic profile of topical 3H-Mipragoside on 48/80 model was investigated and compared with untreated animals. Mipragoside treatment significantly reduced (p < 0.05 vs placebo) the conjunctival vasopermeability induced by reverse passive Arthus reaction as well as successfully reduced the eosinophil levels in the conjunctival epithelium (p < 0.01 vs placebo) elicited by compound 48/80. Further, Mipragoside successfully reduced the primary signs of ocular inflammation produced by horse serum administration. A radiotracer technique was used to evaluate the disposition of 3H-Mipragoside in the rabbit ocular tissues. Disposition of the drug was monitored at 30, 60, 120 and 240 min. 3H-Mipragoside levels in the inflamed conjunctiva were significantly higher (p < 0.01) than in the control eye.
Animals↗
[IGM rheumatoid factor occurrence with recurrence of polyarthritis and psoriasis after treatment with interferon alpha].
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Arthritis↗
[Assessment of portal hypertension in hepatic cirrhosis in relation to etiologic factors].
Hundred-forty-one patients, 78 affected by alcoholic liver cirrhosis and 63 by posthepatitic cirrhosis were studied in order to assess the degree of portal hypertension in liver cirrhosis of different etiology taking into account the developing stages of the disease. Etiological assessment was based on anamnesis, laboratory data, needle liver biopsy and patients of each group were divided into 3 subgroups (grade A, B, C) according to Child-Turcotte classification. A > 1.3 cm diameter of portal vein and a > 13 cm spleen size evaluated by means of real-time ultrasonography together with the occurrence of esophageal varices at endoscopy were considered as signs of portal hypertension. Our study shows that such signs are more frequent in patients affected by posthepatitic cirrhosis in comparison with those affected by alcoholic cirrhosis. If the severity of the disease was considered, at the early stage (grade A) no significant difference was reported in portal diameters while splenomegaly and esophageal varices appeared more frequent in posthepatitic cirrhosis. In grade B patients the increase of portal and spleen size proved significantly greater in posthepatitic cirrhosis whereas prevalence of esophageal varices was similar in the two groups. The lack of differences in the three considered parameters at the end stage of the disease may be due to severe changes in liver morphology actually similar in the 2 groups apart from etiological factors.
Adult↗