Our results indicate that trans-resveratrol-3-O-glucuronide and trans-resveratrol-3-sulfate are the most abundant metabolites of resveratrol. Virtually no unconjugated resveratrol was detected in urine or serum samples, which might have implications regarding the significance of in vitro studies that used only unconjugated resveratrol.

Rhabdomysarcoma is the most common soft tissue tumour in children under the age of 15. Although the introduction of multimodal treatment programmes, including chemotherapy, radiation therapy and excision have increased the overall survival, the chemotherapeutic agents currently used for the treatment of rhabdomyosarcoma exhibit considerable toxicity. The aim of this study was to investigate the effects and possible mechanism(s) of action of resveratrol on human embryonal rhabdomyosarcoma (RD) cells. Resveratrol is a natural polyphenolic compound produced in a number of edible plants and has received considerable attention as a potential chemopreventive and/or chemotherapeutic agent against various types of cancers. In the present study, resveratrol was shown to inhibit cell proliferation of RD cells in a dose-dependent manner with an IC50 of 48.1 micromol/l and induce an arrest in the S/G2 phase of the cell cycle. As evident from immunocytochemical data, resveratrol treatment increased the size of the RD cells. Furthermore, resveratrol treatment resulted in a significant downregulation of cyclin B expression as demonstrated by western blot analyses. In conclusion, the present study shows that resveratrol exerts a strong inhibition of rhabdomyosarcoma cell proliferation in part by arresting cells in S/G2 phase of the cell cycle. These findings warrant further investigation to establish potential use of resveratrol as a relatively non-toxic chemotherapeutic agent for the treatment of rhabdomyosarcoma.

The intrathecal penetration of N-formimidoyl thienamycin (MK0787) with or without coadministration of the renal dipeptidase enzyme inhibitor (MK791) in normal rabbits was studied immediately before and after the third dose of 40 mg/kg infused intravenously at daily 6-h intervals. Mean ± standard error peak concentrations in cerebrospinal fluid were 0.23 ± 0.02 and 0.53 ± 0.12 ,ug/ml without and with coadministration of MK791, respectively (P < 0.05, Student's t test). Penetration into cerebrospinal fluid (based on the ratio of cerebrospinal fluid to plasma area under the concentration-time curves) were 4.4 and 6.0%, respectively. N-Formimidoyl thienamycin penetrated uninflamed meninges, and peak concentrations were significantly augmented by coadministration of MK791.N-Formimidoyl thienamycin (MK0787) has potent activity against both gram-positive and gram-negative bacteria and might be useful for treatment of bacterial meningitis (5). N-Formimidoyl thienamycin is unique among 1-lactam antibiotics in that it is metabolized and inactivated in the brush border of the renal tubules by the dipeptidase enzyme, dehydropeptidase I, which hydrolyzes the P-lactam ring (4). The degradation of N-formimidoyl thienamycin in vivo can be halted and its concentration in urine and plasma augmented by the coadministration of a renal dipeptidase inhibitor (MK-791) in chimpanzees and humans (4). Accordingly, we studied the intrathecal penetration of N-formimidoyl thienamycin in rabbits with or without coadministration of MK791.Groups of New Zealand White female rabbits weighing 2 to 3 kg each were studied. Each rabbit was adapted in individual cages for 48 h before experimentation. Anesthesia was attained by intramuscular ketamine hydrochloride (100 mg/ml) admixed with acepromazine maleate (2.5 mg/ml). N-Formimidoyl thienamycin at a dose of 40 mg/kg alone or in combination with MK791 at a dose of 40 mg/kg was administered at 6-h intervals by intravenous bolus infusion through anterior marginal ear veins. N-Formimidoyl thienamycin (Merck Sharp search Laboratories, Rahway, N.J.) was prepared in sterile normal saline. Antibiotic solutions containing MK791 (Merck Sharp & Dohme Research Laboratories) were prepared by admixing stock solutions of N-formimidoyl thienamycin and MK791 in a water bath maintained at 80°C. Approximately 2.5 ml of plasma and 0.5 to 1 ml of cerebrospinal fluid (CSF) were obtained at each sampling from the anterior ear veins and cistemal space, respectively, immediately before and at 0.5, 1, 2, 4, and 6 h after the third dose of antibiotic. No bloody samples were accepted for analysis. All samples were immediately stabilized in MES (50%o [vol/vol]