Activity of Paraoxonase/Arylesterase and Butyrylcholinesterase in Peripheral Blood of Gulf War Era Veterans With Neurologic Symptom Complexes or Post-Traumatic Stress Disorder.

OBJECTIVE: Two groups of Gulf War era veterans, one exhibiting blurred vision, balance problems/dizziness, tremors/shaking, and speech difficulty and a second group with post-traumatic stress disorder (PTSD), but not the neurologic syndrome, were assessed for organophosphate-detoxifying enzyme paraoxonase/arylesterase (PON1) and its Q/R isoforms, butyrylcholinesterase (BuChE) and its U/A isoforms and cytokines. METHODS: Defibrinated peripheral blood was evaluated for enzymes and cytokines. RESULTS: Trends toward elevation of Th2 cytokines interleukin-4 (IL-4) and IL-13 were observed in subjects with neurologic syndrome. Neither the activities nor isoforms of the enzyme, the neurologic symptoms, nor PTSD had any relationship to wartime deployment to the theater of combat. CONCLUSION: The negative outcomes described above suggest that exposure to organophosphates or other agents normally detoxified by PON1 and BuChE may not have contributed significantly to neurologic components of Gulf War Illness.

Neonatal cytokines and cerebral palsy in very preterm infants.

To examine the relationship of cytokines in blood of very preterm neonates with later diagnosis of spastic cerebral palsy (CP) compared with infants of similar gestational age without CP, we measured concentrations of inflammatory cytokines and other substances in archived neonatal blood by recycling immunoaffinity chromatography. Subjects were surviving children born before 32 wk gestational age (GA) to women without preeclampsia, 64 with later diagnoses of CP and 107 control children. The initial analyses were augmented by measurement of 11 cytokines by a bead-based flow analytic system (Luminex) in an additional 37 children with CP and 34 control children from the same cohort. Concentrations of examined substances did not differ by presence of indicators of infection in mother, infant, or placenta. On ANOVA, concentrations of a number of cytokines were significantly related to neonatal ultrasound abnormalities (periventricular leukomalacia, ventricular enlargement, or moderate or severe germinal matrix hemorrhage). None of the substances measured either by immunoaffinity chromatography or flow analytic methods, including IL-1, -6, and -8 and tumor necrosis factor-alpha, was related to later diagnosis of CP or its subtypes. Inflammatory cytokines in neonatal blood of very premature infants did not distinguish those with later diagnoses of CP from control children.

Antioxidant and lysosomotropic properties of acridine-propranolol: protection against oxidative endothelial cell injury.

The antioxidant and lysosomotropic properties of a fluorescent analogue of propranolol, 9-amino-acridine-propranolol (9-AAP) were compared to those of propranolol. Using isolated microsomal membranes exposed to a superoxide and hydroxyl radical generating system, 9-AAP was found to be at least 10-fold more potent than propranolol (and about 50% as potent as vitamin E) in inhibiting lipid peroxidation. In cultured endothelial cells, 9-AAP afforded moderate protective effect against acute loss of glutathione but potent cytoprotective activity against free radical-mediated loss of viability/survival. Intracellular localization of 9-AAP was examined by fluorescent microscopy and compared with two known fluorescent lysosomal markers: acridine orange and Lysosensor. All three agents appeared to localize to similar peri-nuclear vesicles, presumably lysosomes or pre-lysosomes. Lysosensor fluorescence was not observable in the presence of 9-AAP, foreclosing the possibility of a direct dual labeling experiment. We employed the pH sensitivity of acridine orange to determine if it labels the same vesicles as 9-AAP. When the endothelial cells were preloaded with acridine orange, washed and resuspended in buffer containing 9-AAP, the dark orange-labeled vesicles observed with acridine orange alone became increasingly lighter with time. Since the fluorescence of acridine orange is altered by pH change, this spectral shift in fluorescence emission is consistent with the indication that added propranolol (or the analog) leads to lysosomal alkalization. In conclusion, 9-AAP is both a strong antioxidant and a lysosomotropic agent that is remarkably insensitive to photobleaching. These properties may contribute to the enhanced endothelial cytoprotective effects against free radical-induced injury.