Daniela Lombardi

Inhibition of epidural fibrosis with ADCON-L: effect on clinical outcome one year following re-operation for recurrent lumbar radiculopathy.

In a prospective multicenter study, 20 patients underwent re-operation for recurrent radiculopathy after lumbo-sacral discectomy, and were treated with ADCON-L (Adhesion Control in a Barrier Gel) to inhibit epidural fibrosis following secondary surgery. Outcomes after re-operation were assessed at six and 12 months using: Visual Analog Scales to measure radicular and back pain, straight leg raising exams, and self-assessment of activity-related radicular pain. Each parameter was compared to baseline values, obtained immediately prior to the re-operation. The long term clinical results at 12 months after re-operation (summarized below) demonstrate a significant improvement of all clinical parameters, and correlated with the results seen at six months. Radicular pain, measured when most severe, was reduced from an average pre-operative score of 8.1-3.7 (p < 0.005). The straight leg raising angle increased from an average pre-operative value of 41 degrees-67 degrees (p < 0.005). Activity-related pain mean score was 4.6, vs. 17.0 pre-operatively (p < 0.005). Low back pain, measured when most severe, was reduced from an average pre-operative score of 6.1 to 3.1 (p < 0.012). These clinical findings compare very favorably with data reported in the literature. There were no adverse events or complications related to the use of ADCON-L.

Experimental subarachnoid hemorrhage : lipid peroxidation and Na+, K+-ATPase in different rat brain areas

Subarachnoid hemorrhage (SAH) was produced in Sprague Dawley rats by injection of 0.30 mL of autologous arterial blood into the cisterna magna. Tissue lipid peroxide, quantified as thiobarbituric acid reactive material (TBAR), and Na+,K(+)-ATPase activity were assayed in three different rat brain areas (cerebral cortex, hippocampus, and brain stem) of sham-operated rats and in four hemorrhagic rat groups at 30 min, 1 h, 6 h, and 2 d after SAH. Na+,K(+)-ATPase activity decreased in the cerebral cortex at 30 min, 1 h, and 6 h and in the brain stem at 1 h after SAH induction, whereas enzymatic activity was unchanged in the hippocampus. There was no evident difference in lipid peroxide content between sham-operated animals and hemorrhagic animals. These results indicate that little modifications in lipid peroxidative process (as expressed in TBAR) are not responsible for changes in the ATPase activity.

Effect of high-dose methylprednisolone and U74006F on eicosanoid synthesis after subarachnoid hemorrhage in rats.

Free radicals and lipid peroxidation of membrane fatty acids are thought to play a role in the pathogenesis of arterial vasospasm and the physiopathologic patterns of neuronal damage after subarachnoid hemorrhage. We have evaluated the effects of treatment with either high-dose methylprednisolone every 8 hours or a single dose of U74006F on the temporal profile of ex vivo synthesis of four selected eicosanoids in brain slices after experimental induction of subarachnoid hemorrhage in rats. Prostaglandins D2 and E2, prostacyclin and leukotriene C4 levels were determined by radioimmunoassay after 1-hour incubation of the brain slices. The synthesis of prostaglandin D2 and 6-ketoprostaglandin F1 alpha at 48 hours after subarachnoid hemorrhage was significantly higher when compared to sham-operated animals (p = 0.01); prostaglandin E2 release was significantly enhanced at 6 hours after subarachnoid hemorrhage (p = 0.01). The release of the lipoxygenase metabolite was significantly enhanced at 1, 6, and 48 hours after subarachnoid hemorrhage induction. Both treatment regimens significantly reduced the ex vivo synthesis of prostaglandin D2, prostaglandin E2, and leukotriene C4 at 1, 6, and 48 hours after subarachnoid hemorrhage, whereas the effects on 6-ketoprostaglandin F1 alpha synthesis differed in the two treatment groups. U74006F enhanced the synthesis of prostacyclin metabolite in the early phase after subarachnoid hemorrhage, and high-dose methylprednisolone reduced the increasing synthesis at 48 hours. A strict comparison between the two treatments was not possible because of the different modalities of administration. However, these data suggest that the antioxidant effect of single-dose treatment with U74006F influenced the early and delayed effects on enzymatic lipid peroxidation, whereas the effects of methylprednisolone administration every 8 hours were more significant in the delayed phase.

Effect of high-dose methylprednisolone on anti-oxidant enzymes after experimental SAH

Lipid peroxidation has been considered one of the most important factors involved in the pathogenesis of neuronal damage following subarachnoid hemorrhage. In the brain, the protective systems most involved against peroxidative and free radicals generated reactions are superoxide-dismutase (SOD) and glutathione-peroxidase (GSH-Px). Since these activities are subjected to a significant reduction following experimental SAH induction in rats, we investigated in the present study if the beneficial effect of high-dose methylprednisolone (MP) in inhibiting lipid peroxidative processes in SAH is possibly linked to an influence on anti-oxidant enzymatic activities. In brain cortex, after MP treatment, Cu-Zn SOD activity in the early phase and more dramatically in the late phase after SAH was restored (4.06 +/- 0.06 and 4.07 +/- 0.14 enzymatic units/mg of protein, respectively) if compared to hemorrhagic non-treated controls (3.69 +/- 0.16 and 2.96 +/- 0.06 enzymatic U/mg of protein) while Mn-SOD and GSH-Px activities were improved in treated animals only in the early and late phases after SAH, respectively. In the hippocampus, in treated rats Cu-Zn activity was partially restored only at 6 h, while Mn-SOD activity recovered at 48 h after SAH; no significant changes in GSH-Px activity were found in treated animals at any time. In the brain stem, in treated animals, Cu-Zn SOD activity was restored in the early phase (3.86 +/- 0.12 enzymatic U/mg of protein) up to control values of non-hemorrhagic rats (3.44 +/- 0.30 enzymatic U/mg of protein), while GSH-Px activity recovered in the late phase.(ABSTRACT TRUNCATED AT 250 WORDS)

EFFECT OF NICARDIPINE ON ANTIOXIDANT ENZYMATIC ACTIVITIES AND LTC4 RELEASE IN EXPERIMENTAL SAH

Modifications of biochemical and physiological parameters following subarachnoid hemorrhage (SAH) such as the activation of lipid peroxidation and liberation of free radicals (1,2), variations in scavenger enzyme activities (3), and the enhancement of arachidonic acid metabolism (4) could be considered indicators of brain damage in evolution after SAH. An impaired homeostasis of Ca2+ and its relationship with lipid-peroxidative processes has been largely studied with special regards for the pathogenesis of arterial vasospasm and its ischemic consequences.

Phosphatases and cathepsin D activities after vasogenic oedema: an experimental study.

The role of two phosphatases (acid and alkaline phosphatase) and a lysosomal aspartyl endopeptidase (cathepsin D) in producing rat brain oedema was studied in 3 different rat cerebral areas (i.e. frontal cortex, hippocampus and striatum) at 1, 2 and 3 d after vasogenic brain oedema induction. The percentage of water content in the frontal cortex increased immediately, 1 d after oedema induction and remained high for 2 and 3 d after oedema induction. In the hippocampus and the striatum the water content only increases 3 d after oedema induction. In the oedematous hemisphere (right), when compared to the contralateral hemisphere (left), the acid phosphatase activity decreases in the hippocampus, while the alkaline phosphatase increases in the frontal cortex and striatum; cathepsin D increases only in the striatum. The changes caused by the enzymatic activities were significant only 2 and 3 d after oedema induction. The results of this study show that: (i) the vasogenic oedema induced in experimental conditions was not sufficient to cause a massive liberation of lysosomal enzymes and (ii) brain areas adjacent (below) to the site of the experimental oedematous lesion (frontal cortex) were influenced by oedema induction.