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The study aims to evaluate and compare the efficacy of the use of ethosuximide, valproic acid, and lamotrigine in the treatment of childhood absence epilepsy. The results indicate that ethosuximide and valproic acid are more effective, and that ethosuximide is associated with fewer adverse effects.

Valproic acid (VPA) is widely used to treat epilepsy and manic-depressive illness. Although VPA has been reported to exert a variety of biochemical effects, the exact mechanisms underlying its therapeutic effects remain elusive. To gain further insights into the molecular mechanisms of VPA action, a genetic screen for fission yeast mutants that show hypersensitivity to VPA was performed. One of the genes that we identified was [vps45.sup.+], which encodes a member of the Sec1/Muncl8 family that is implicated in membrane trafficking. Notably, several mutations affecting membrane trafficking also resulted in hypersensitivity to VPA. These include [ypt3.sup.+] and [ryh1.sup.+], both encoding a Rab family protein, and [apm1.sup.+], encoding the [micro]1 subunit of the adaptor protein complex AP-1. More importantly, VPA caused vacuolar fragmentation and inhibited the glycosylation and the secretion of acid phosphatase in wild-type cells, suggesting that VPA affects membrane trafficking. Interestingly, the cell-wall-damaging agents such as micafungin or the inhibition of calcineurin dramatically enhanced the sensitivity of wild-type cells to VPA. Consistently, VPA treatment of wild-type cells enhanced their sensitivity to the cell-wall-digesting enzymes. Altogether, our results suggest that VPA affects membrane trafficking, which leads to the enhanced sensitivity to cell-wall damage in fission yeast.

Byline: S. AltunbasA,ak (1), Dincer YA+-ldA+-z (2), A. Anarat (3), H. Refik Burgut (4) Keywords: KeywordsaValproic acid; Renal tubular function; [beta]2-Microglobulin; N-Acetyl-[beta]-d-glucosamine; Malondialdehyde Abstract: To investigate the effects of valproic acid (VPA) on renal tubular function, we examined 15 ambulatory children with epilepsy who received VPA for at least 6 months. None of the patients had mental retardation. Fourteen age- and sex-matched children were used as a control group. No statistically significant differences were found between patients and control subjects with respect to blood urea nitrogen (BUN), creatinine (Cr), uric acid, creatinine clearance (C.sub.cr), tubular reabsorption of phosphorus (TRP), urinary Ca:creatinine ratio, urinary pH and mean urinary [beta].sub.2-microglobulin concentrations (P&gt 0.05). Protein and glucose in patient urine samples were negative. Urine microscopic examinations and amino acid chromatographies of patients were also normal. However, significant differences were found between patient and control groups with respect to mean urinary N-acetyl-beta-d-glucosamine:creatinine ratio (NAG:Cr) and mean urinary malondialdehyde:creatinine (MDA:Cr) ratio (P&lt 0.05). In conclusion, ambulatory children with epilepsy taking VPA therapy may develop proximal renal tubular dysfunction. Although this finding is clini-cally insignificant, it should be kept in mind during VPA therapy. Author Affiliation: (1) Department of Pediatric Neurology, Cukurova University Medical Faculty, 01330 Balcali-Adana, Turkey e-mail: sakira@mail.cu.edu.tr Tel.: +90-322-3386936, Fax: +90-322-3386572, TR (2) Resident in Pediatrics, Cukurova University Medical Faculty, Adana, Turkey, TR (3) Department of Pediatric Nephrology, Cukurova University Medical Faculty, Adana, Turkey, TR (4) Department of Biostatistics, Cukurova University Medical Faculty, Adana, Turkey, TR Article note: Received: 11 November 1999 / Revised: 21 September 2000 / Accepted: 26 October 2000

Results of a study to evaluate and compare the efficacy of the use of ethosuximide, valproic acid, and lamotrigine in the treatment of childhood absence epilepsy have revealed that ethosuximide and valproic acid are more effective, and that ethosuximide is associated with fewer adverse effects. The study has shown that the oldest of the three therapies was the most effective.

Byline: Hossein. Sanaei-Zadeh Sir, I read with interest, the recent case presentation by Nasa et al . regarding the effectiveness of hemodialysis in a case of severe valproate overdose published [...]

The use of valproate in pregnant women with epilepsy is associated with a higher risk of impaired cognitive function in their children at age three, according to researchers at Emory [...]