Low leucocyte myeloperoxidase activity in patients with multiple sclerosis

The gene for myeloperoxidase (MPO) has been implicated in multiple sclerosis (MS). By measuring H2O2 dependent oxidation of 3,3'5,5'-tetramethylbenzidine with spectrophotometry the authors investigated MPO activity in peripheral blood leucocytes from 42 patients with MS (12 with secondary progressive MS, 17 with primary progressive MS, and 13 with relapsing remitting benign MS) and 32 healthy controls. Leucocyte MPO activity was significantly lower in patients with benign MS (mean (SEM) 0.086 (0.029) U/mg protein;

Plasma lipid peroxidation and progression of disability in multiple sclerosis

Oxidative stress has been implicated in the pathophysiology of multiple sclerosis (MS), but its relation to disease progression is uncertain. To evaluate the relationship of plasma lipid peroxidation with progression of disability in MS, we measured blood plasma fluorescent lipid peroxidation products (PFLPP) levels in 23 patients with RRMS with a benign course, 32 with secondary progressive MS, 24 with primary progressive MS and 30 healthy controls. None of the patients had a relapse within the previous 3 months. Progression of disability was evaluated during a follow-up period of 5 years by the Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Severity Score (MSSS). We found plasma PFLPP levels elevated in patients with MS compared with controls (P <0.0001), but there was no difference between patients with a benign and progressive disease course. There was no correlation between PFLPP levels and worsening of disability on the EDSS and speed of progression on the MSSS. Our data suggest that there is no relation between the degree of oxidative stress in plasma and progression of disability in MS

Plasma homocysteine levels in multiple sclerosis

Background: There is evidence that homocysteine contributes to various neurodegenerative disorders, and elevated plasma homocysteine levels have been observed in patients with multiple sclerosis (MS). Objective: To investigate if and why plasma homocysteine levels are increased in MS, and whether they play a role in the disease course. Methods: We compared plasma levels of homocysteine in 88 patients with MS and 57 healthy controls. In the MS group, 28 had a benign course, 37 were secondary progressive, and 23 primary progressive. To explore the underlying mechanisms, we measured serum levels of vitamins B-6 and B-12, folate, interleukin (IL)-12, tumour necrosis factor (TNF)-alpha, leukocyte nitric oxide production, and plasma diene conjugate levels (measure of oxidative stress). Results: Mean (SD) plasma homocysteine concentration was higher in patients (13.8 (4.9) mu mol/l) than in controls (10.1 (2.5) mu mol/l; p Conclusions: Elevated plasma homocysteine occurs in both benign and progressive disease courses of MS, and seems unrelated to immune activation, oxidative stress, or a deficiency in vitamin B-6, vitamin B-12, or folate

Maternal Hyperhomocysteinemia Disturbs the Mechanisms of Embryonic Brain Development and Its Maturation in Early Postnatal Ontogenesis

Maternal hyperhomocysteinemia causes the disruption of placental blood flow and can lead to serious disturbances in the formation of the offspring’s brain. In the present study, the effects of prenatal hyperhomocysteinemia (PHHC) on the neuronal migration, neural tissue maturation, and the expression of signaling molecules in the rat fetal brain were described. Maternal hyperhomocysteinemia was induced in female rats by per os administration of 0.15% aqueous methionine solution in the period of days 4–21 of pregnancy. Behavioral tests revealed a delay in PHHC male pups maturing. Ultrastructure of both cortical and hippocampus tissue demonstrated the features of the developmental delay. PHHC was shown to disturb both generation and radial migration of neuroblasts into the cortical plate. Elevated Bdnf expression, together with changes in proBDNF/mBDNF balance, might affect neuronal cell viability, positioning, and maturation in PHHC pups. Reduced Kdr gene expression and the content of SEMA3E might lead to impaired brain development. In the brain tissue of E20 PHHC fetuses, the content of the procaspase-8 was decreased, and the activity level of the caspase-3 was increased; this may indicate the development of apoptosis. PHHC disturbs the mechanisms of early brain development leading to a delay in brain tissue maturation and formation of the motor reaction of pups

2001: Melatonin increases both life span and tumor incidence in female CBA mice. The Journals of Gerontology

From the age of 6 months until their natural deaths, female CBA mice were given melatonin with their drinking water (20 mg/l) for 5 consecutive days every month. Intact mice served as controls. The results of this study show that the consumption of melatonin did not significantly influence food consumption, but it did increase the body weight of older mice; it did not influence physical strength or the presence of fatigue; it decreased locomotor activity and body temperature; it inhibited free radical processes in serum, brain, and liver; it slowed down the agerelated switching-off of estrous function; and it increased life span. However, we also found that treatment with the used dose of melatonin increased spontaneous tumor incidence in mice. For this reason, we concluded that it would be premature to recommend melatonin as a geroprotector for long-term use