In vitro effects of 1-(4-dimethylaminobenzylidene)-2-(2-hydroxybenzylidene) hydrazine and its copper complex on lymphocyte proliferation and function in the presence of free radical generator.

In this study, the in vitro effects of 1-(4-dimethylaminobenzylidene)-2-(2-hydroxybenzylidene) hydrazone (L1) and its corresponding copper complex [Cu(L1)], synthesized in our laboratory, were investigated on the proliferative responses, Th1 (interleukin-2 (IL-2), interferon-γ (INFγ)) and Th2 (IL-4) cytokine secretion, adenosine triphosphate (ATP) levels and intracellular redox status of T lymphocytes submitted to H2O2/FeSO4-mediated oxidative stress. T cells were isolated on histopaque density gradient by differential centrifugation, and were cultured with the mitogen concanavalin A (Con A), free radical generator (H2O2/FeSO4) and with different concentrations of L1 and [Cu(L1)] (1 - 100 µM). Proliferation (MTT assay), cytokines (Elisa kits), ATP levels, cytotoxic effect (micronucleus test) and oxidative markers (glutathione, catalase, superoxide dismutase, hydroperoxide and carbonyl protein contents) were investigated after 48-h incubation. Our results showed that H2O2/FeSO4 treatment induced a reduction in T lymphocyte proliferation, cytokine secretion and ATP levels associated to an evident intracellular oxidative stress, inflammatory profile and DNA damage. Addition of L1 at 100 µM was able to increase cell proliferation, IL-2, IL-4 and INFγ secretion and ATP contents and to reduce hydroperoxide and carbonyl protein contents, catalase activity and micronuclei number in lymphocytes under oxidative stress, with a partial protection. The [Cu(L1)] exhibited protective effects in T lymphocytes by inhibiting H2O2/FeSO4 - induced cell proliferation suppression, inflammatory status, ATP loss and oxidative stress generation, whatever the concentration used. In conclusion, in the situation of excessive oxidative stress, [Cu(L1)] treatment improved T lymphocyte proliferation, cytokine production, ATP contents and oxidant/antioxidant status. [Cu(L1)] could be effective at improving oxidative stress and T cell abnormalities.

[Paroxysmal dystonia and multiple sclerosis]. / Dystonie paroxystique et sclérose en plaques.

INTRODUCTION: Movement disorders are uncommon in multiple sclerosis, except for tremor. Patients rarely have paroxysmal dystonia (or tonic spasm), which can be the presenting manifestation of the disease. OBSERVATIONS: Two videotaped observations are presented. The first patient was a 27-year-old woman, treated for relapsing-remitting multiple sclerosis, who presented daily several short (<1minute) paroxysms of right hemibody dystonia. Brain MRI revealed several areas of cerebral demyelination, including the posterior limb of the left internal capsule with gadolinium enhancement. These events disappeared 7 days after corticosteroid infusion. The second patient was a 62-year-old man who presented brief episodes (<1minute) of daily painful left hemibody dystonia. Three months later, similar paroxysms affecting the right hemibody including the face occurred. At times, the two hemibodies were affected simultaneously. The brain MRI showed multiple areas of white matter hyperintensity, including two symmetrical areas in the posterior limb of the internal capsules. Multiple sclerosis was diagnosed on clinical, MRI and biological data. Four days after starting corticosteroids, these paroxysmal phenomena disappeared totally. CONCLUSION: Dystonia is an under-recognized aspect of paroxysmal events during multiple sclerosis. It might involve ephaptic transmission among abnormal demyelinated neurons; this ectopic excitation can arise at variable levels of the corticospinal tract, but the analysis of reported cases and those described in this study shows that impairment of the posterior limb of the internal capsule seems to be a prevalent topography. Inflammation is likely to play a role because steroids often improve these phenomena. In this article, we review the clinical aspects, pathophysiology and outcome of paroxysmal dystonia in multiple sclerosis.

Pharmaco-economic study of intensive chemotherapy with peripheral blood progenitor cell support for advanced breast cancer.

Patients with high-risk breast cancer may benefit from dose-escalated chemotherapy. The rationale for high-dose chemotherapy with stem-cell rescue (HDC-SCR) in breast cancer is based on the principles of dose response and dose intensity. However, several results of properly randomized and prospective studies are necessary to determine the interest of HDC-SCR. The objective of this study, realised in the Anticancer Center of Montpellier, was to evaluate the cost of this type of transplantation. In this retrospective study, we analysed 30 patients treated for an advanced breast cancer between October 1995 and June 1998. We collected the data from the induction chemotherapy cycle (followed by cytapheresis) to the end of the hospitalisation for autograft. The mean total cost was US $25,845 per patient: US $6453 for drugs, US $4720 for transfusions, US $1865 for laboratory services and blood tests, US $5585 for staff pay, US $774 for material, US $1211 for administration cost, US $1111 for logistic cost, US $998 for structure cost and US$1578 for other. Antibiotics, granulocyte-colony stimulating factor, chemotherapy, transfusions and nutrition represent respectively 18% (US $1962), 14% (US $1590), 13% (US $1437), 42% (US $4720), 11% (US $1191) of the medication and blood products cost. The results of this study may help in identifying targets for cost reduction.