Sweets from the pharmaceutical industry reason to suspect intoxication with quetiapine

A 13-year-old boy was presented to the emergency department with a presumed intoxication with quetiapine, an antipsychotic. The tablets turned out to be peppermints, used as advertisement gift from the pharmaceutical industry. This misunderstanding could have led to unnecessary treatment and observation of the patient in hospital, for a moderately serious intoxication.     

Immunomodulatory and antimetastatic action of propolis and related polyphenolic compounds

The effect of polyphenolic compounds isolated from propolis and propolis itself was investigated on the growth and metastatic potential of a transplantable mammary carcinoma (MCa) of CBA mouse. Metastases in the lung were generated by intravenous injection of tumor cells (2 x 10(5)). A water-soluble derivative of proplis (WSDP), caffeic acid (CA), caffeic acid phenethyl ester (CAPE) and quercetin (QU) were given to mice per os before tumor cells inoculation. Tested compounds significantly decreased the number of tumor nodules in the lung. According to the results obtained the antitumor activity of tested compounds can be related to the immunomodulatory properties of the compounds, their cytotoxicity to tumor cells, and their capacity to induce apoptosis and necrosis. The experimental data support that WSDP, CA, CAPE and QU could be potentially useful in the control of tumor growth in experimental models.     

Pharmacological basis for the gut stimulatory activity of Raphanus sativus leaves

The crude extract of Raphanus sativus leaves (Rl.Cr) showed a dose-dependent (0.03-5.0 mg/ml) spasmogenicity in guinea-pig ileum and colon. The effect was insensitive to atropine pre-treatment but was completely abolished by pyrilamine indicating involvement of histaminergic (H(1)) receptors. The contractile effect at high doses (3.0-5.0mg/ml) was followed by relaxation. Rl.Cr also enhanced the transit of charcoal meal in mice at 30-100 mg/kg. The petroleum spirit, chloroform and aqueous fractions all showed histaminergic activity in ileum; aqueous fraction being more potent. The study shows the presence of a histaminergic component(s) along with a weak spasmolytic factor thus providing sound mechanistic basis for the traditional use of the plant in constipation.     

Direct assessment of drug penetration into tissue using a novel application of three-dimensional cell culture

The failure of many anticancer drugs to control growth of solid cancers may stem in part from inadequate delivery to tumor regions distant from vasculature. Although the identification of new anticancer drug targets has led to the development of many new drug candidates, there is a lack of methodology for identifying drugs that adequately penetrate tumor tissue. We have developed a novel multilayered cell culture-based assay, which detects the penetration of anticancer drugs based on their effect within tissue. Drug exposures are made over 1 hour to one side of a disk of tissue approximately 150-microm thick, with the other side temporarily closed off, and penetration is then assessed 1-3 days later via bromodeoxyuridine-based detection of S-phase cells. Using this assay, the tissue distribution of a selection of anthracycline analogues was assessed. At clinically relevant exposures, none of the agents were able to affect cells on the far side of the culture at levels approaching that seen on the near (exposed) side. Doxorubicin and epirubicin exhibited approximately 10-fold decreases in the drug exposure seen by the cells on the far side relative to those on the near side of the cultures, whereas for daunorubicin and mitoxantrone, approximately 30-fold and >30-fold decreases were observed respectively. Results were consistent with the observed gradients in drug-derived fluorescence of doxorubicin, epirubicin, and daunorubicin. This model could be applied as a simple anticancer drug development screen to discover drugs that exhibit desirable penetration properties.     

Dose-dependent effects of platelet-derived growth factor-B on glial tumorigenesis

Platelet-derived growth factor (PDGF) is expressed in many different tumors, but its precise roles in tumorigenesis remain to be fully defined. Here, we report on a mouse model that demonstrates dose-dependent effects of PDGF-B on glial tumorigenesis. By removing inhibitory regulatory elements in the PDGFB mRNA, we are able to substantially elevate its expression in tumor cells using a retroviral delivery system. This elevation in PDGF-B production results in tumors with shortened latency, increased cellularity, regions of necrosis, and general high-grade character. In addition, elevated PDGF-B in these tumors also mediates vascular smooth muscle cell recruitment that supports tumor angiogenesis. PDGF receptor (PDGFR) signaling appears to be required for the maintenance of these high-grade characteristics, because treatment of high-grade tumors with a small molecule inhibitor of PDGFR results in reversion to a lower grade tumor histology. Our data show that PDGFR signaling quantitatively regulates tumor grade and is required to sustain high-grade oligodendrogliomas.