Dose finding and O6-alkylguanine-DNA alkyltransferase study of cisplatin combined with temozolomide in paediatric solid malignancies

Cisplatin may have additive activity with temozolomide due to ablation of the DNA repair protein O6-alkylguanine-DNA alkyltransferase (MGMT). This phase I/II study determined recommended combination doses using the Continual Reassessment Method, toxicities and antitumour activity in paediatric patients, and evaluated MGMT in peripheral blood mononuclear cells (PBMCs) in order to correlate with haematological toxicity. In total, 39 patients with refractory or recurrent solid tumours (median age ∼13 years; 14 pretreated with high-dose chemotherapy, craniospinal irradiation, or having bone marrow involvement) were treated with cisplatin, followed the next day by oral temozolomide for 5 days every 4 weeks at dose levels 80 mg m−2/150 mg m−2 day−1, 80/200, and 100/200, respectively. A total of 38 patients receiving 113 cycles (median 2, range 1–7) were evaluable for toxicity. Dose-limiting toxicity was haematological in all but one case. Treatment-related toxicities were thrombocytopenia, neutropenia, nausea-vomiting, asthenia. Hearing loss was experienced in five patients with prior irradiation to the brain stem or posterior fossa. Partial responses were observed in two malignant glioma, one brain stem glioma, and two neuroblastoma. Median MGMT activity in PBMCs decreased after 5 days of temozolomide treatment: low MGMT activity correlated with increased severity of thrombocytopenia. Cisplatin–temozolomide combinations are well tolerated without additional toxicity to single-agent treatments; the recommended phase II dosage is 80 mg m−2 cisplatin and 150 mg m−2 × 5 temozolomide in heavily treated, and 200 mg m−2 × 5 temozolomide in less-heavily pretreated children

Chronic administration of the delta opioid receptor agonist (+)BW373U86 and antidepressants on behavior in the forced swim test and BDNF mRNA expression in rats

Selective delta opioid receptor agonists have been shown to produce antidepressant-like behavioral effects and increase brain-derived neurotrophic factor (BDNF) mRNA expression when given acutely, but the chronic effects of delta agonists have been less well characterized.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46371/1/213_2005_Article_113.pd

Spinning disk reactor technology in photocatalysis: nanostructured catalysts intensified production and applications

The use of photocatalysis in environmental remediation processes has become more important in the last decade, mainly due to the notable efforts made by researchers in this field. The photocatalytic process requires a semiconductor material (photocatalyst), usually a metal oxide, which can be activated through the energy transported by ultraviolet light or visible light waves. The activated photocatalyst generates active compounds, such as hydroxyl radicals and superoxide ion, able to degrade very recalcitrant and non-biodegradable compounds present on the catalyst surface or in the liquid medium. The efficiency of the pollutant removal process is affected by various factors related to the employed photocatalyst, such as mean dimension, size distribution, physical structure and energy required for the activation. The photocatalyst characteristics are strongly dependent on the production process, and several researchers have developed new intensified production nanostructured catalysts in a continuous Spinning Disk Reactor is discussed. The main features of Spinning Disk Reactor technology are reported and analysed, i.e. rotational velocity, disk diameter, disk surface material and roughness, focusing on the production of nanoparticles to be used in the photocatalytic application, in view of the process intensification of photocatalysis application in the field of environmental remediation. A general overview about process intensification and its application to chemical engineering is presented, and the advantages offered by Spinning Disk Reactor technology, in terms of an increase of process efficiency due to the misinformation of operative conditions in reactors, are illustrated. Basing on the Spinning Disk Reactor characteristics and operative conditions, nanoparticle production by Spinning Disk Reactor compared to conventional technologies and the current application of this technology to selected nanoparticles (titania, magnetite, MgO and hydroxyapatite), synthesis is discussed. Spinning Disk Reactor technology allows to produce active semiconductor particles, characterized by a mean size significantly below 100 nm and with a narrow unimodal distribution, improving the quality of these products in comparison with those produced through conventional processes and equipment. Finally, the application of vertical and horizontal Spinning Disk Reactor configuration to the degradation of refractory compounds by photocatalysis is reviewed, aiming at evaluating process efficiency and the produced nanoparticle characteristics, to assess the key parameters and the limiting factors of the technology