Survival of children with malignant brain tumors receiving valproate: a retrospective study.

PURPOSE: The treatment of pediatric patients with malignant brain tumors has evolved considerably in the past decades. However, results are still unsatisfactory for some patients. Valproate has been shown to positively affect the survival of adult glioblastoma patients. We have been giving prophylactic antiepileptic drugs to newly diagnosed children with brain tumors. Since then, we noted a trend towards a better survival from our patients. In order to study this, we performed a retrospective evaluation in our institution. METHODS: Standard survival analysis was used, calculating survival until death by all causes or censoring. Comparisons were made by Cox's proportional hazards model regression. RESULTS: Between 2000 and 2010, 94 patients were treated (12 with high-grade gliomas, 56 medulloblastomas, and 26 ependymomas); median and mean ages were 7.7 and 7.8 years. Median follow-up was 60 months (35 for treated and 109 for untreated patients). Of these, 47 received valproate 10-15 mg/kg/day every 8-12 h and 47 did not. Patients who received valproate had a median survival of 34 months, whereas the other group had a median survival of 24 months (hazard ratios = 0.99, 0.57-1.75, p = 0.99). CONCLUSIONS: These results do not prove that valproate prophylactic treatment in pediatric patients with malignant brain tumors had an influence on their survival. However, our cohort showed an effect of higher size than the recent European Organization for Research and Treatment of Cancer trial analysis, even though not significant. Clinical trials with valproate in pediatric malignant brain tumors should be carefully planned, in order to detect a possible effect of this drug in survival.

Studies on the anti-oedematogenic properties of a fraction rich in lonchocarpin and derricin isolated from Lonchocarpus sericeus.

The acute anti-inflammatory properties of a fraction rich in the chalcones lonchocarpin and derricin, from the roots of Lonchocarpus sericeus (HFLS), were studied for the first time, using a paw oedema model induced in rats by various stimuli. Results showed that HFLS (100 and 200 mg kg(-1), i.p.) was ineffective in inhibiting dextran-induced paw oedema. The HFLS (200 mg kg(-1), p.o. or i.p.) also failed to inhibit the bradykinin-induced oedema. In the yeast-elicited oedema, the HFLS (200 mg kg(-1), i.p.) caused inhibitions ranging from 42 to 59% in the first to fourth hours. Orally administered HFLS (200 mg kg(-1)) was active only in the second (27%) and fourth (32%) hours after yeast injection. It was observed that HFLS (50, 100 and 200 mg kg(-1), i.p.) showed inhibitions of 34, 57 and 74%, respectively, in the third hour for the carrageenan-induced oedema. The inhibition was smaller when the HFLS (100 and 200 mg kg(-1)) was administered orally. The effect of the HFLS (20 mg kg(-1), i.p.) in the carrageenan-induced oedema was not modified by the L-NAME, but the association of pentoxifylline and HFLS increased its effect, suggesting an involvement of the PDE enzyme.

Anti-inflammatory and smooth muscle relaxant activities of the hydroalcoholic extract and chemical constituents from Amburana cearensis A C Smith.

Amburana cearensis A. C. Smith, Fagaceae, is a medicinal plant commonly known as 'cumaru' and used in Northeast Brazil for the treatment of respiratory tract diseases. In the present work, we investigated the anti-inflammatory and smooth muscle relaxant activities of the hydroalcoholic extract (HAE), coumarin (Coum) and fl avonoid fraction (FF) isolated from the trunk barks of Amburana cearensis A. C. Smith. It was shown that HAE (200 and 400 mg/kg), Coum (20 and 40 mg/kg) and FF (40 mg/kg), administered orally, significantly inhibited both leukocyte and neutrophil migrations, in the carrageenan or N-formyl-methyl-leucyl-phenylalanine (fMLP)-induced migration in rat peritoneal cavity. The increase in cutaneous vascular permeability induced by serotonin in rats was significantly blocked by HAE (150 mg/kg, i.p.), Coum (5 mg/kg, i.p.) and FF (20 mg/kg, i.p.). However, only HAE blocked the histamine effect on Evans blue extravasation. In the guinea-pig trachea precontracted with carbachol (0.3 microM), histamine (0.1 microM) or KCl (0.1 M), the HAE, Coum and FF evoked a concentration-dependent relaxation in the presence of the three agonists. HAE (100-800 microg/ml) and Coum (4-32 microg/ml) also caused significant relaxation of the rat vas deferens previously contracted with adrenaline, acetylcholine or barium chloride. In addition, HAE, Coum and FF inhibited the histamine and serotonin-induced increase of cutaneous vascular permeability in rats.

The analgesic and anti-inflammatory effects of shark cartilage are due to a peptide molecule and are nitric oxide (NO) system dependent.

The present work shows an antinociceptive and dose-dependent effect of shark cartilage hydrosoluble fraction (HF) on writhing and formalin tests in mice. The effect was not altered by thalidomide, a known inhibitor of tumor necrosis factor-alfa (TNF-alfa) synthesis. Similarly, the antinociceptive effect did not change in the presence of naloxone, indicating that the opioid system is not involved. However, the effect observed was blocked by L-arginine, a NO synthesis substrate, and it was potentiated by L-NAME, suggesting a role of the NO system in the shark cartilage antinociceptive effect. Effects similar to those seen with the HF were detected with peak II from gel filtration chromatography. The increase in vascular permeability induced by serotonin in rats was significantly abolished by the HF at the dose of 2 mg/kg, p.o., and again it was not potentiated by thalidomide. The observed blockade in the vascular permeability increase induced by histamine was detected only with a higher dose (10 mg/kg, p.o.).

Anti-inflammatory and analgesic activity of a water-soluble fraction from shark cartilage.

The anti-inflammatory and analgesic activities of a water-soluble fraction (WSF), extracted with 0.1 M ammonium bicarbonate, pH 8.0, from shark cartilage were studied in several experimental models. Orally administered WSF (10 mg/kg) caused 25.7 and 23.6% inhibition of the paw edema produced in female Wistar rats (200-250 g) by carrageenan and dextran, respectively, after 3 h, as compared to controls. WSF administered orally had no effect on acetic acid-induced writhings in male Swiss mice (25-30 g) at the dose of 0.01 mg/kg but caused 52.8 and 61.4% inhibition at the doses of 0.1 and 0.5 mg/kg, respectively, compared to controls (No. of writhings/20 min, means +/- SEM: treated groups = 18.6 +/- 2.5, N = 12 and 15.2 +/- 1.4, N = 12, respectively; controls = 39.3 +/- 1.3, N = 77). In the formalin test (male Swiss mice, 25-30 g), orally administered WSF (0.5 and 1 mg/kg) caused 12.0 and 46.6% inhibition of licking time, respectively, only in the 2nd phase (inflammatory) of the test (licking time, means +/- SEM: treated group = 18.3 +/- 4.4 sec, N = 7 and 11.1 +/- 3.4 sec, N = 13; controls = 20.8 +/- 2.4 sec, N = 44). The results suggest that a molecule of a protein nature in shark cartilage is probably responsible for the effects observed.

Anti-inflammatory and analgesic activity of a water-soluble fraction from shark cartilage

The anti-inflammatory and analgesic activities of a water-soluble fraction (WSF), extracted with 0.1 M ammonium bicarbonate, pH 8.0, from shark cartilage were studied in several experimental mod-els. Orally administered WSF (1O mg/kg) caused 25.7 and 23.6 per cent inhibition of the paw edema produced in female Wistar rats (200-250 g) by carrageenan and dextran, respectively, after 3 h, as compared to controls. WSF administered orally had no effect on acetic acid-induced writhings in male Swiss mice (25-30 g) at the dose of 0.01 mg/kg, but caused 52.8 and 61.4 per cent inhibition at the doses of 0.1 and 0.5 mg/kg, respectively, compared to controls (No. of writhings/20 min, means ñ SEM: treated groups = 18.6 ñ 2.5, N = 12 and 15.2 ñ 1.4, N = 12, respectively; controls = 39.3 ñ 1.3, N = 77). In the formalin test (male Swiss mice, 25-30 g), orally administered WSF (0.5 and 1 mg/kg) caused 12.0 and 46.6 per cent inhibition of licking time, respectively, only in the 2nd phase (infiammatory) of the test (licking time, means ñ SEM: treated group = 18.3 ñ 4.4 sec, N = 7 and 11.1 ñ 3.4 sec, N = 13; controls = 20.8 ñ 2.4 sec, N = 44). The results suggest that a molecule of a protein nature in shark cartilage is probably responsible for the effects observed.