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Clinical Trial 2003; 24(1-2): 57-64 PubMed PMID: 12743534 Citation  Keywords:  Humans, Hypersensitivity:diagnosis, Immunization, Lymphocyte Activation, Lymphocytes:immunology, Metals, Patch Tests, Reproducibility of Results,.   

OBJECTIVE: This study was carried out to evaluate the reproducibility, sensitivity, specificity, and reliability of the MELISA Test for detecting metal sensitivity in patients with clinical symptoms of a type IV hypersensitivity to metal.

DESIGN: Blood from 250 patients was tested in MELISA against up to 20 different metals in 2 to 3 concentrations. The frequency and distribution of metal reactivities, the sensitivity and specificity of nickel reactivity in patients with and without confirmed or suspected sensitivity to nickel, and the roles of lymphocyte concentration and concentration of inorganic mercury were analyzed. In addition, for reproducibility testing, 196 metal tests were performed in duplicate, and intra- and interassay variations of MELISA results were examined in patients patch-test positive for the relevant metal.

RESULTS: Among the 250 patients, reactivity to 0, 1, 2, 3, 4, or > or = 5 metals was 26%, 36%, 15%, 12%, 6%, and 5%, respectively. Reactivity was most frequent to nickel (73%), followed by titanium (42%), cadmium (18%) gold (17%), palladium (13%), lead (11%), beryllium (9%), inorganic mercury (8%), tin (8%), and phenylmercury (6%). All patients (n=15) with confirmed or suspected nickel allergy were positive in MELISA, while patients with no suspicion of nickel allergy were either negative (n=6) or very low positive (n=4) in MELISA. MELISA reactivity is directly dependent on lymphocyte concentration: the higher the lymphocyte concentration per test, the stronger the reactivity. Concentrations of inorganic mercury > 0.5 microg/ml cause non antigen-specific (mitogenic) reactions in a majority of patients. The reproducibility rate was 94% using a cut-off of Stimulation Index > or = 3 or 99% using a cut-off of > or = 5. While the absolute intra- and interassay Stimulation Index values may vary, the qualitative results are highly reproducible.

CONCLUSION: The MELISA Test is reproducible, sensitive, specific, and reliable for detecting metal sensitivity in metal-sensitive patients....

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Journal Article 2002; 23(5-6): 411-416 PubMed PMID: 12500162 Citation  Keywords:  Animals, Cell Division:drug effects, Cell Membrane:chemistry, Cerebral Cortex:chemistry, Concanavalin A:pharmacology, Crosses, Genetic, Enzyme Activation:drug effects, Interleukin-1:metabolism, Lymphocyte Activation:drug effects, Male, Mice, Mice, Inbred .   

OBJECTIVES: The aim of this research consisted in studying the effects of tetrapeptide Epitalon on both thymocyte proliferation and interleukin-1beta (IL-1beta) signal transduction via sphingomyelin pathway in the cerebral cortex membranes of mice exposed to stresses exerting diverse effects upon humoral immune response.

DESIGN AND SETTING: The experiments were performed on male (CBAxC(57)BL(6))F1 mice aged 8 10 weeks. Two models of experimental stress were used: immune-stimulatory rotation stress and immune-suppressive combined stress (cooling followed by immobilization). The concomitant effect of Epitalon was determined according to its influence on thymocyte proliferation stimulated by concanavalin A at a sub-optimal dose and recombinant IL-1beta. The activity of membrane neutral sphingomyelinase (nSMase), the key enzyme of the sphingomyelin signal transduction pathway, was assayed according to modified Rao and Spence's method (1976).

RESULTS: The investigation demonstrated that Epitalon increased thymocyte proliferative activity, both enhanced under rotation stress and suppressed under combined one. It also increased IL-1beta concomitant effect. These findings corresponded to Epitalon effect on diverse stress-induced changes in nSMase activity in cerebral cortex fraction P2. Epitalon activated nSMase in the cerebral cortex membranes of intact mice and increased IL-1beta stimulatory effect on the enzyme activity.

CONCLUSIONS: The obtained results provided a conclusive evidence of Epitalon stress-protective effect at the level of IL-1beta signal transduction via sphingomyelin pathway in the nerve tissue, as well as at the level of target thymocyte proliferation....

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Clinical Trial 2002; 23(3): 255-258 PubMed PMID: 12080288 Citation  Keywords:  Aged, Antineoplastic Agents:administration & dosage, Carcinoma, Renal Cell:drug therapy, Drug Therapy, Combination, Female, Humans, Injections, Subcutaneous, Interleukin-2:administration & dosage, Kidney Neoplasms:drug therapy, Lymphocyte Count, Male, Mid.   

OBJECTIVES: Recent advances in knowledge of Psychoneuroimmunology have shown that several neuroactive substances, including neurohormones and neuropeptides, may exert immunomodulatory effects. However, despite the great variety of potential neuroimmune interactions, at present we may recognize two major neuroendocrine systems exerting a physiological neuroimmunomodulatory function, consisting of the pineal gland and the brain opioid system, provided by immunostimulatory and immunosuppressive effects, respectively. Recent in human studies have demonstrated the possibility to amplify the biological activity of IL-2, the major anticancer cytokine, by pineal indoles.

MATERIALS & METHODS: The present study was carried out to draw some preliminary in human results on the possible immunomodulatory effects of the inhibition of the brain opioid activity by a long-acting opioid antagonist, naltrexone (NTX). The study was performed in 10 metastatic renal cell cancer patients, who had progressed on a previous immunotherapeutic cycle with IL-2 alone. Patients were treated with the same doses of IL-2 (6 million lU/day subcutaneously for 6 days/week for 4 weeks) plus an oral administration of NTX at a dose of 100 mg every 2 days.

RESULTS: The clinical response consisted of a partial response in 1 and a stable disease in 5 patients, whereas the other 4 patients progressed. Therefore, the percent of non-progressive disease was 6/10 (60%). Moreover, mean lymphocyte increase achieved during IL-2 plus NTX was significantly higher (P<0.05) than that obtained during the previous treatment with IL-2 alone.

CONCLUSIONS: This study shows that a blockade of the brain opioid system, which plays a physiological immunosuppressive role, may improve the anticancer effects of IL-2 in humans....

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Journal Article 2002; 23(Suppl 1): 67-72 PubMed PMID: 12019355 Citation  Keywords:  Animals, Antioxidants:pharmacology, Cell Division:drug effects, Cell Membrane:drug effects, Cells, Cultured, Chickens:physiology, Colforsin:pharmacology, Cyclic AMP:metabolism, Lymphocytes:drug effects, Male, Melatonin:pharmacology, Phytohemagglutinins:ph.   

OBJECTIVES: Time-dependent melatonin effects on chicken lymphocyte proliferation in vitro and the involvement of cAMP in melatonin signal transduction were examined.

MATERIALS AND METHODS: Splenocytes and peripheral blood mononuclear cells (PBMC) were cultured in vitro in the presence of melatonin, phytohemagglutinin, luzindole, dibutyrylcAMP (dbcAMP), forskolin and vasoactive intestine peptide (VIP). Proliferation was measured by [(3)H]-thymidine incorporation in cultures carried out for 24, 36, 48 and 72 h. Cyclic AMP formation was assessed by radioimmunoassay in cells incubated for 30 min. or 24 h.

RESULTS: Melatonin stimulated the spontaneous proliferation in short-term (36 and 48 h) splenocyte cultures and had no effect in 72 h cultures. It inhibited mitogen-stimulated proliferation already in 24 h cultures and this effect was observed regardless of the time of the culture. Both melatonin effects were antagonized by luzindole - membrane-bound melatonin receptor antagonist. Forskolin and dbcAMP caused a significant inhibition of proliferation of splenocytes and PBMC cultured for 24 or 72 h, respectively. Melatonin inhibited the cAMP formation (30 min. of incubation) stimulated by adenosine cyclase activators - forskolin and VIP, but added alone failed to affect the cAMP concentration. In mitogen-stimulated splenocytes cultured for 24 h Mel caused an increase in cAMP correlated with the inhibition of cell proliferation.

CONCLUSIONS: Melatonin effects on chicken splenocytes appears time- and activation-dependent: in short-term cultures it stimulates spontaneous and inhibits mitogen-activated proliferation, probably via membrane-bound, luzindole-sensitive melatonin receptors. Incubation with melatonin for 30 min. inhibits cAMP formation, but in 24 h cultures it increases cAMP concentration leading to inhibition of proliferation....

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