Free radical scavenging activities measured by electron spin resonance spectroscopy and B16 cell antiproliferative behaviors of seven plants.

In an effort to discover new antioxidant natural compounds, seven plants that grow in France (most of them in the Limousin countryside) were screened. Among these plants, was the extensively studied Vitis vinifera as reference. For each plant, sequential percolation was realized with five solvents of increasing polarities (hexane, chloroform, ethyl acetate, methanol, and water). Free radical scavenging activities were examined in different systems using electron spin resonance (ESR) spectroscopy. These assays were based on the stable free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH), the hydroxyl radicals generated by a Fenton reaction, and the superoxide radicals generated by the X/XO system. Antiproliferative behavior was studied on B16 melanoma cells. ESR results showed that three plants (Castanea sativa, Filipendula ulmaria, and Betula pendula) possessed, for the most polar fractions (presence of phenolic compounds), high antioxidant activities in comparison with the Vitis vinifera reference. Gentiana lutea was the only one that presented a hydroxyl scavenging activity for the ethyl acetate and chloroform fractions. The antiproliferative test results showed that the same three plants are the most effective, but for the apolar fractions (chloroform and hexane).

Redifferentiation therapy in brain tumors: long-lasting complete regression of glioblastomas and an anaplastic astrocytoma under long term 1-alpha-hydroxycholecalciferol.

PURPOSE: Classical and new therapies in anaplastic astrocytomas and glioblastomas do not yield sufficient results. Agents able to redifferentiate neoplastic cells in vitro are known. We proposed alfacalcidol, a vitamin D analog able to bind to nuclear receptors regulating mitotic activity, in the treatment of malignant gliomas. PATIENTS AND METHODS: Patients with glioblastomas and anaplastic astrocytomas were enrolled in a phase II trial involving surgery or biopsy, radiotherapy (64 Gy), chemotherapy with VM26-CCNU or fotemustine, and alfacalcidol at the daily dose of 0.04 microg/kg. MRI took place every 6 months. RESULTS: Eleven patients were included and completed the study. The series involved 10 glioblastomas and 1 anaplastic astrocytoma. Three patients out of 11 patients (27%), 2 glioblastomas and 1 astrocytoma grade III, exhibited a particular response, consisting in the progressive regression of the radiological lesion, with a decrease of the gadolinium-enhanced area. Simultaneously, the patients showed a complete clinical remission, observed respectively for 7, 5 and 4 years. In the series of 10 patients with glioblastomas, 2 cases showed this response; after 4 years, 2 of 10 patients with glioblastomas (20%) were alive; the median survival time is 21 months. Normal or subnormal calcemia was observed, at the dose proposed, so that no interruption of the drug was necessary. CONCLUSIONS: Alfacalcidol, an in vitro agent of redifferentiation, is safe and seems able to induce in some patients, in synergy with classical surgery-radiotherapy-chemotherapy treatments, a particular progressive and durable regression of the tumor. The responders might represent about 20% of malignant gliomas.

Ursolic acid triggers calcium-dependent apoptosis in human Daudi cells.

Ursolic acid (UA) is a pentacyclic triterpenoid compound which occurs naturally in a large variety of vegetarian foods, medicinal herbs and plants. In the present study, ursolic acid was found to decrease cell viability in human lymphoma Daudi cells in a dose-dependent manner. UA also induced morphological changes in cells as well as loss of membrane asymmetry, DNA fragmentation and nuclei condensation, indicating that the mechanism by which UA induced cell death was through apoptosis. Treatment with UA increased intracellular Ca2+ levels. Use of Ca2+ channel inhibitors like verapamil blocked this Ca2+ influx and also the triggering of apoptosis. We hypothesized that the binding of UA to glucocorticoid receptors and the Ca2+ currents induced constituted the first steps of apoptosis.

Hyperbaric oxygen in the treatment of acute ischemic stroke: an unsettled issue.

Therapy for acute ischemic stroke can be approached in two basic ways: first, by an attempt to restore or improve blood flow in an occluded vascular territory and, second, via therapy directed at the cellular and metabolic targets. As local anoxia and energy failure are the initiating cellular stage in ischemia, the inhalation of oxygen at increased atmospheric pressures might be effective. Treatment of acute focal cerebral ischemia with hyperbaric oxygen (HBO) has been reported in animals and humans. In general, the results of research in animals have suggested a promising role for the use of HBO. More than 400 cases of human ischemic stroke treated with HBO have been reported. In about half of the cases, improvement in status has been claimed on clinical or electroencephalographic grounds. In fact, the effectiveness of HBO in most disease processes other than carbon monoxide poisoning and decompression sickness is a subject of major ongoing debate. This short review will attempt: (1) to recall some early experiments involving HBO in the treatment of acute ischemia: (2) to point out some conflicting results regarding the role of HBO on cellular and metabolic disorders; and (3) to determine the possibility of a future role for HBO therapy in acute ischemic stroke.

Hyperbaric oxygen in the treatment of acute ischemic stroke. A double-blind pilot study.

BACKGROUND AND PURPOSE: The effects of hyperbaric oxygen (HBO) therapy on humans are uncertain. Our study aims first to outline the practical aspects and the safety of HBO treatment and then to evaluate the effect of HBO on long-term disability. METHODS: Patients who experienced middle cerebral artery occlusion and were seen within 24 hours of onset were randomized to receive either active (HBO) or sham (air) treatment. The HBO patients were exposed daily to 40 minutes at 1.5 atmospheres absolute for a total of 10 dives. We used the Orgogozo scale to establish a pretreatment functional level. Changes in the Orgogozo scale score at 6 months and 1 year after therapy were used to assess the therapeutic efficacy of HBO. In addition, we used the Rankin scale and our own 10-point scale to assess long term-disability at 6 months and 1 year. Two sample t tests and 95% confidence intervals were used to compare the mean differences between the two treatment groups. Student's two-tailed test was used to compare the differences between pretherapeutic and posttherapeutic scores at 6 months and 1 year in the two treatment groups. RESULTS: Over the 3 years of study enrollment, 34 patients were randomized, 17 to hyperbaric treatment with air and 17 to hyperbaric treatment with 100% oxygen. There was no significant difference at inclusion between groups regarding age, time from stroke onset to randomization, and Orgogozo scale scores. Neurological deterioration occurred during the first week in 4 patients in the sham group, 3 of whom died; this worsening was clearly related to the ischemic damage. Treatment was also discontinued for 3 patients in the HBO group who experienced myocardial infarction, a worsening related to the ischemic process, and claustrophobia. Therefore, 27 patients (13 in the sham group and 14 in the HBO group) completed a full course of therapy. The mean score of the HBO group was significantly better on the Orgogozo scale at 1 year (P < .02). However, the difference at 1 year between pretherapeutic and posttherapeutic scores was not significantly different in the two groups (P < .16). Moreover, no statistically significant improvement was observed in the HBO group at 6 months and 1 year according to Rankin score (P < .78) and our own 10-point scale (P < .50). CONCLUSIONS: Although the small number of patients in each group precludes any conclusion regarding the potential deleterious effect of HBO, we did not observe the major side effects usually related to HBO. Accordingly, it can be assumed that hyperbaric oxygen might be safe. We hypothesize that HBO might improve outcome after stroke, as we detected an outcome trend favoring HBO therapy. A large randomized trial might be required to address the efficacy of this therapy.

[Early and middle latency auditory evoked potentials in vertebrobasilar strokes]. / Potentiels évoqués auditifs précoces et de latence moyenne dans les accidents vasculaires vertébrobasilaires.

Brainstem auditory evoked potentials (BAEPs) and middle-latency auditory evoked potentials (MLAEPs) have been recorded in 67 patients who had a stroke in well-defined territories of the vertebral and basilar arteries. Either CT scan or MRI have been performed in all cases. BAEPs were abnormal in 41/67 patients and MLAEPs were abnormal in 25/39 patients. BAEPs abnormalities were either bilateral (29/41 cases) or unilateral (12/41 cases). All components of BAEPS were unilaterally absent in four cases and bilaterally in one case. Pa component of MLAEPs was unilaterally delayed or reduced in five cases and bilaterally in 20 cases. Considering the topography of the infarct as shown by CT scan or MRI: medulla oblongata (13 cases): BAEPSs were normal in nine cases; pons (24 cases): BAEPs were abnormal in 16 cases; MLAEPs were abnormal in ten of 15 patients whose BAEPs were abnormal as well; mesencephalon (seven cases): BAEPs were abnormal in only two cases, and MLAEPs were abnormal in two cases one of which BAEPs were normal; in patients with diffuse infarctions either BAEPs or MLAEPs or both were abnormal in all cases. Stimulation of the ear ipsilateral to the lesion disclosed more BAEPs or MLAEPs abnormalities than stimulation of the contralateral ear.