Summary Our previous experimental studies have shown that the best approach to increase the biological anti-tumour activity of interleukin 2 (IL-2) is not co-administration of another cytokine, but the association with immunomodulating neurohormones, in an attempt to reproduce the physiological links between psychoendocrine and immune systems, which play a fundamental role in the regulation of the immune responses. In particular, the association with the pineal neurohormone melatonin (MLT) has been shown to cause tumour regressions in neoplasms that are generally non-responsive to IL-2 alone. To confirm these preliminary results, a clinical trial was performed in locally advanced or metastatic patients with solid tumours other than renal cell cancer and melanoma. The study included 80 consecutive patients, who were randomised to be treated with IL-2 alone subcutaneously (3 million IU day-' at 8.00 p.m. 6 days a week for 4 weeks) or IL-2 plus MLT (40 mg day-' orally at 8.00 p.m. every day starting 7 days before IL-2). A complete response was obtained in 3/41 patients treated with IL-2 plus MLT and in none of the patients receiving IL-2 alone. A partial response was achieved in 8/41 patients treated with IL-2 plus MLT and in only 1/39 patients treated with IL-2 alone. Tumour objective regression rate was significantly higher in patients treated with IL-2 and MLT than in those receiving IL-2 alone (11/41 vs 1/39, P<0.001). The survival at 1 year was significantly higher in patients treated with IL-2 and MLT than in the IL-2 group (19/41 vs 6/39, P<0.05). Finally, the mean increase in lymphocyte and eosinophil number was significantly higher in the IL-2 plus MLT group than in patients treated with IL-2 alone; on the contrary, the mean increase in the specific marker of macrophage activation neopterin was significantly higher in patients treated with IL-2 alone. The treatment was well tolerated in both groups of patients. This study shows that the concomitant administration of the pineal hormone MLT may increase the efficacy of low-dose IL-2 subcutaneous therapy.
Genetic risk factors seem to play a role in sporadic Parkinson's disease (PD), maybe triggering oxidative stress and excitotoxicity within substantia nigra. However, genetic factors act at systemic level: reduced activity of mitochondrial enzymes and decreased glutamate uptake have been shown in platelets from PD patients. In this study we investigated glutamate uptake in platelets from 38 sporadic PD patients, 13 patients with parkinsonian syndromes and 28 controls and assessed polymorphisms of alpha-synuclein and ApoE genes. A 48% reduction of glutamate uptake p)<0.0001) was observed in PD patients which, with respect to control groups, correlated with the disease severity (r = -0.44, p < 0.05). Genetic studies of this population did not show differences between PD and controls, nor correlations with platelet glutamate uptake.
Finding a biomarker could help physicians to formulate a correct diagnosis and thus in choosing the best therapeutic strategy. In this work, we analyzed the role of tryptase serum concentrations to differentiate real allergic syndromes from the HFP syndrome, which causes similar histamine-mediated effects by a different mechanism.
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