Impaired expression of erythrocyte glycosyl-phosphatidylinositol-anchored membrane CD59 in patients with psoriatic arthritis. Relation to terminal complement pathway activation

OBJECTIVE: Complement-mediated injury is regulated by many factors; among these CD59 has been identified as a widely distributed glycoprotein that inhibits membrane C5b-9 (terminal complement component) formation. The aim of the study was to assess erythrocyte CD59 expression in patients with psoriatic arthritis in order to understand the role of CD59 in the pathogenesis. METHODS: Washed erythrocytes from 50 patients with psoriatic arthritis, 8 with cutaneous psoriasis and 24 healthy subjects were incubated with monoclonal anti-CD59 antibody followed by a second FITC conjugated antibody and fluorescence intensity analysed by FAC-Scan flow cytometer to assess their CD59 membrane expression. SC5b-9 levels were measured in the plasma by ELISA and results compared with CD59 values. Immune complexes, complement C3 and C4 and rheumatoid factor were also determined. RESULTS: Impaired expression of erythrocyte membrane-anchored CD59 was found in patients with psoriatic arthritis; the lowest levels were seen in active patients (p < 0.01). Increased SC5b-9 was seen in the plasma of patients with active disease. An inverse correlation was also found between plasma C5b-9 and the CD59 expression levels (r = -0.81, p < 0.001). CONCLUSION: The low CD59 expression on erythrocytes from patients with psoriatic arthritis may be an index of a low tissue CD59 expression. This impairment could facilitate the activation of complement pathway and increase the risk for arthritis. Membrane attack complex formation in deficient membrane bound CD59 may also exacerbate synovial cell injury and inflammation.     

IL-1β at the crossroad between rheumatoid arthritis and type 2 diabetes: may we kill two birds with one stone?

Although in the past the prevention of joint destruction in rheumatoid arthritis (RA) was strongly emphasized, now a great interest is focused on associated comorbidities in these patients. Multiple data suggest that a large percentage of RA patients are affected by Type 2 Diabetes (T2D), whose incidence has reached epidemic levels in recent years, thus increasing the health care costs. A better knowledge about the pathogenesis of these diseases as well as the mechanisms of action of drugs may allow both policy designers and physicians to choose the most effective treatments, thus lowering the costs. This review will focus on the role of Interleukin (IL)-1β in the pathogenesis of both the diseases, the efficacy of IL-1 blocking molecules in controlling these diseases, and will provide information suggesting that targeting IL-1β, in patients affected by both RA and T2D, may be a promising therapeutic choice.     

An examination of the synergistic interaction of ethanol and thiamine deficiency in the development of neurological signs and long-term cognitive and memory impairments

BACKGROUND: The prolonged and heavy consumption of ethanol has been associated with thiamine deficiency and a wide range of cognitive and memory impairments. The present study was undertaken to test the hypothesis that ethanol and thiamine deficiency act synergistically, producing more severe clinical neurological disturbances and cognitive and memory impairments than either thiamine deficiency or chronic ethanol alone. METHODS: The acute neurological and long-term behavioral consequences of combined chronic (32 weeks) ethanol consumption (20% v/v in drinking water) and three separate 4-week long episodes of dietary thiamine deficiency (ET/TD) versus ethanol (ET) or thiamine deficiency (TD) treatments alone were examined in male Sprague Dawley rats aged 12 weeks at the start of treatment. RESULTS: The ET/TD group lost less weight than the TD group during each episode of thiamine deficiency. Contrary to expectations, the progression and severity of ataxia, impaired righting reflexes, and opisthotonic posturing were similar in the ET/TD and TD groups. None of the ET animals displayed any neurological or behavioral symptoms during treatment. After withdrawal from ethanol and a 7-week recovery period, none of the groups differed in spontaneous activity. On subsequent testing, the ET group displayed a significant increase in perseverative responding in a spontaneous alternation task. A small but significant proportion of ET/TD (23%), ET (17%), and TD (8%) animals were unable to reach criterion on an initial nonmatching-to-position task (NMTP) or in two subsequent reversals of the matching and NMTP tasks, which indicated persistent learning impairments. A large proportion of animals in each of the three groups demonstrated significantly reduced accuracy compared with controls at longer delays of matching-to-position tasks (MTP), but only the ET group was consistently impaired at the shorter delays. There were no significant correlations between blood ethanol concentration and any of the learning and memory measures. CONCLUSIONS: These results indicate that the interaction of chronic ethanol consumption and bouts of TD is both domain specific and not always synergistic. Learning and reference memory appear to be sensitive to a synergistic interaction of ET and TD, whereas short-term working memory disturbances are most affected by ET and neurological symptoms are most associated with TD. Furthermore, neither the presence of neurological symptoms nor blood ethanol concentrations appear to be good predictors of learning and memory deficits.     

Cytotoxic and DNA interaction activities of extracts from medicinal plants used in Argentina

Eight crude extracts from seven Argentine plants with cancer-related ethnobotanical uses have been subjected to a bioscreening study to detect cytotoxic activity. The plants studied were: Aristolochia triangularis, Baccharis grisebachii, Bolax gummifera, Eupatorium hecatanthum, Erythrina crista-galli, Pterocaulon polystachium and Salpichroa origanifolia. Crown gall tumour inhibition, DNA interaction and cytotoxicity towards KB cells were assayed using the potato disc, the DNA-methyl green (DNA-MG) and the KB cells cytotoxicity bioassays respectively. The results obtained indicate that A. triangularis (ED50=47 microg/ml), B. gummifera (ED50=32 microg/ml) and E. hecatanthum (ED50=35 microg/ml) contained cytotoxic compounds against KB cells. All of the plants studied inhibited the growth of crown gall tumours, showing correlation between the experimental data and the uses reported for these plants. Moreover, the results obtained for the extracts of E. hecatanthum and P. polystachium indicate the presence of compounds that interact with DNA (48 and 22% of absorbance decrease, respectively). The results obtained suggest that cytotoxicity could play an important role in the activities claimed for the plants under study.     

Prevalence of headache in patients with Behçet's disease without overt neurological involvement

The aims of the present study were to evaluate the prevalence of headache and the frequency of different headache syndromes in patients with Beh?et's Disease (BD) without neurological involvement and to investigate the relationship with other clinical, and behavioural variables. Twenty-seven BD patients and 27 control subjects underwent a validated semistructured questionnaire based on the International Headache Society criteria. Levels of anxiety and depression, disease activity, and current medication were collected. Headache occurred in 88.9% of BD patients. There was no difference in the prevalence of the different headache syndromes between BD patients and controls. Only migraine without aura (MwA) was significantly more frequent in BD patients than controls (44.4% vs. 11.1%, respectively, P= 0.013). No relationship was found between MwA and clinical, and behavioural variables. Among headache syndromes, MwA showed the highest frequency in BD. A vascular or neuronal subclinical dysfunction could justify this association. A careful interview for migraine might be included in the diagnostic work-up of BD.     

H‐ferritin and proinflammatory cytokines are increased in the bone marrow of patients affected by macrophage activation syndrome

Macrophage activation syndrome (MAS) is hyperinflammatory life‐threatening syndrome, associated typically with high levels of serum ferritin. This is an iron storage protein including heavy (H) and light (L) subunits, categorized on their molecular weight. The H‐/L subunits ratio may be different in tissues, depending on the specific tissue and pathophysiological status. In this study, we analysed the bone marrow (BM) biopsies of adult MAS patients to assess the presence of: (i) H‐ferritin and L‐ferritin; (ii) CD68⁺/H‐ferritin⁺ and CD68⁺/L‐ferritin⁺; and (iii) interleukin (IL)‐1β, tumour necrosis factor (TNF) and interferon (IFN)‐γ. We also explored possible correlations of these results with clinical data. H‐ferritin, IL‐1β, TNF and IFN‐γ were increased significantly in MAS. Furthermore, an increased number of CD68⁺/H‐ferritin⁺ cells and an infiltrate of cells co‐expressing H‐ferritin and IL‐12, suggesting an infiltrate of M1 macrophages, were observed. H‐ferritin levels and CD68⁺/H‐ferritin⁺ cells were correlated with haematological involvement of the disease, serum ferritin and C‐reactive protein. L‐ferritin and CD68⁺/L‐ferritin⁺ cells did not correlate with these parameters. In conclusion, during MAS, H‐ferritin, CD68⁺/H‐ferritin⁺ cells and proinflammatory cytokines were increased significantly in the BM inflammatory infiltrate, pointing out a possible vicious pathogenic loop. To date, H‐ferritin and CD68⁺/H‐ferritin⁺ were associated significantly with haematological involvement of the disease, suggesting biomarkers assessing severity of clinical picture.