The role of macrophage colony-stimulating factor in patients with acute myocardial infarction: a pilot study

We assessed whether macrophage colony-stimulating factor (M-CSF) levels are associated with left ventricular systolic dysfunction (LVSD) in patients with acute myocardial infarction (AMI). We studied 56 patients with AMI (mean age: 67 ± 12 years) and identified those with clinical (Killip class >II) or echocardiographic signs (ejection fraction ≤45%) of LVSD. We evaluated the established cardiovascular risk factors and measured several cardiovascular biomarkers, including M-CSF. Serum M-CSF concentrations (pg/mL) were significantly increased in patients with both clinical and echocardiographic signs of LVSD (460 ± 265 vs 290 ± 210, P = .0103 and 493 ± 299 vs 287 ± 174, P = .0028, respectively). We found a significant inverse association between M-CSF and ejection fraction (r = -.351, P = .0079). Logistic regression analysis revealed that, among all evaluated clinical and biochemical parameters, the stronger predictor of LVSD was M-CSF (odds ratios 2.1, 95% confidence interval 1.1-2.9, P = .0168). This is the first study reporting plasma M-CSF levels as independent determinants of low LV ejection fraction and clinical LV dysfunction in patients with AMI.     

Dexamethasone exposure and asparaginase antibodies affect relapse risk in acute lymphoblastic leukemia

We have previously hypothesized that higher systemic exposure to asparaginase may cause increased exposure to dexamethasone, both critical chemotherapeutic agents for acute lymphoblastic leukemia. Whether interpatient pharmaco-kinetic differences in dexamethasone contribute to relapse risk has never been studied. The impact of plasma clearance of dexamethasone and anti-asparaginase antibody levels on risk of relapse was assessed in 410 children who were treated on a front-line clinical trial for acute lymphoblastic leukemia and were evaluable for all pharmacologic measures, using multivariate analyses, adjusting for standard clinical and biologic prognostic factors. Dexamethasone clearance (mean ± SD) was higher (P = 3 × 10(-8)) in patients whose sera was positive (17.7 ± 18.6 L/h per m(2)) versus nega-tive (10.6 ± 5.99 L/h per m(2)) for anti-asparaginase antibodies. In multivariate analyses, higher dexamethasone clearance was associated with a higher risk of any relapse (P = .01) and of central nervous system relapse (P = .014). Central nervous system relapse was also more common in patients with anti-asparaginase antibodies (P = .019). In conclusion, systemic clearance of dexamethasone is higher in patients with anti-asparaginase antibodies. Lower exposure to both drugs was associated with an increased risk of relapse.     

Age-related changes in the rat brain mitochondrial antioxidative enzyme ratios: Modulation by melatonin

Oxidative stress is an important factor for aging. The antioxidative enzymes glutathione peroxidase (GPx), glutathione reductase (GRd) and superoxide dismutase (SOD) play a crucial role protecting the organism against the age-dependent oxidative stress. Glutathione (GSH) is present in nearly all living cells. GSH is one of the main antioxidants in the cell and it serves several physiological functions. Our purpose was to evaluate the age-related changes in mitochondrial GPx, GRd and SOD activities, and mitochondrial GSH pool in the brains of young (3months) and aged rats (24months). We also investigated whether melatonin administration influences these brain mitochondrial enzyme activities and GSH levels in young and aged rats. The results showed that GPx activity increased with age, whereas melatonin treatment decreased GPx activity in the aged rats at levels similar to those in young and young+melatonin groups. The activities of GRd and SOD, however, did not change with age. But, melatonin treatment increased SOD activity in the aged rats. GSH levels, which also increased with age, were not modified by melatonin treatment. The reduction in the SOD/GPx and GR/GPx ratios with age was prevented by melatonin administration. Together, our results suggest that the age-related oxidative stress in rat brain mitochondria is more apparent when the antioxidant enzyme ratios are analyzed instead of their absolute values. The antioxidative effects of melatonin were also supported by the recovery of the enzyme ratios during aging.     

Reduced habituation of the retinal ganglion cell response to sustained pattern stimulation in multiple sclerosis patients

ObjectiveSustained pattern stimulation in normal subjects induces adaptive changes in pattern electroretinogram (PERG), an effect that has been interpreted as a response of glial cells and retinal ganglion cells (RGC). The aim of this study was to compare the effect in normal subjects and in multiple sclerosis patients without previous optic neuritis.MethodsPERGs were elicited by a 7.5 Hz pattern stimulus, presented continuously over 152 s. Response cycles were averaged in 20 packets of 60 events each and amplitude and phase of the 2nd harmonic response was measured. Adaptive changes are expressed as amplitude reduction over the full examination time.ResultsIn normal subjects PERG amplitude declined progressively to a plateau (dA = ?0.46 μV, SE = 0.09 μV); in patients the effect size was severely reduced (dA = ?0.20 μV, SE = 0.04 μV). No significant difference was found in mean amplitude.ConclusionsThe results show reduced RGC habituation in patients, suggesting an abnormal gain and sensitivity control in the inner retina, even in absence of clinical optic neuritis. Recent findings in astrocyte biology and indications drawn from a mathematical model point to a key role of glial cells in this process.SignificanceThe proposed methodology may have implications in the assessment of MS patients and in understanding the pathophysiology of neurological and retinal disorders.