Non-amphetaminic mechanism of stimulant locomotor effect of modafinil in mice

Previously established dose-response curves indicated that modafinil 20-40 mg/kg i.p. elicited in mice an obvious stimulation of locomotor activity roughly similar to that induced by (+)amphetamine 2-4 mg/kg. The effects of various agents modifying dopamine transmission were compared on the locomotor response to both drugs. The preferential D2 dopamine receptor antagonist haloperidol 37.5-150 micrograms/kg i.p. suppressed the stimulant effect of (+)amphetamine in a dose dependent manner, but not that of modafinil. The D1 dopamine receptor antagonist SCH 23390 (7.5-30 micrograms/kg s.c.) reversed the (+)amphetamine but not the modafinil induced hyperactivity. The tyrosine hydroxylase inhibitor alpha-methyl-para-tyrosine (200 mg/kg) suppressed the hyperactivity induced by 4 mg/kg dexamphetamine but not that induced by 20 mg/kg modafinil. Associating L-DOPA 150 mg/kg and benserazide 37.5 mg/kg with (+)amphetamine 2 mg/kg resulted in stereotyped climbing behavior, that was not observed with modafinil 10-80 mg/kg. The profound akinesia induced by reserpine (4 mg/kg s.c.; 5 h before testing) was reversed by (+)amphetamine 2 mg/kg but not by modafinil 40 mg/kg. Finally, on synaptosomes prepared from mouse striata preloaded with [3H]dopamine, modafinil 10(-5) M did not increase the spontaneous [3H]dopamine release whereas (+)amphetamine, at the same concentration, doubled it. From all these differences between the two drugs, it is concluded that the mechanism underlying the modafinil induced stimulant locomotor effect differs completely from that of (+)amphetamine.     

Efficient generation of a reshaped human mAb specific for the {alpha} toxin of Clostridium perfringens

We have used the technique of antibody reshaping to producea humanized antibody specific for the a toxin of Clostridiumperfringens. The starting antibody was from a mouse hybridomafrom which variable (V) region nucleo-tide sequences were determined.The complementarity-determining regions (CDRs) from these Vregions were then inserted into human heavy and light chainV region genes with human constant region gene fragments subsequentlyadded. The insertion of CDRs alone into human frameworks didnot produce a functional reshaped antibody and modificationsto the V region framework were required. With minor frameworkmodifications, the affinity of the original murine mAb was restoredand even exceeded. Where affinity was increased, an alteredbinding profile to overlapping peptides was observed. Computermodelling of the reshaped heavy chain V regions suggested thatamino acids adjacent to CDRs can either contribute to, or distort,CDR loop conformation and must be adjusted to achieve high bindingaffinity.     

Recovery from work shifts: How long does it take?

Although regulations on work hours usually include a minimum weekly rest period, there is little empirical evidence concerning recovery from work. Shift-working nurses (N?=?61) used a handheld computer for 28 days to complete self-ratings, cognitive-performance tasks, and a sleep diary. Many measures were worse on rest days that followed a night shift rather than a day shift and tended to be worse on 1st rest days compared with subsequent rest days. Alertness was lowest on the 1st rest day following a night shift. Social satisfaction was better on workdays that were preceded by 2 rather than 1 rest day. Reaction time (RT) decreased over consecutive night shifts and tended to increase over rest days following night shifts. The results are interpreted as being consistent with the combined adaptive costs of fatigue and adjustment to and from a nocturnal routine. The practical implications for scheduling rest days are considered. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A kinetic investigation into the removal of carbobenzyloxy group from protected amines via hydrogenolysis reaction

Hydrogenolysis of a carbobenzyloxy group (CBz) was studied utilizing molecular hydrogen in the presence of carbon-supported palladium catalyst. It was demonstrated that the kinetics of the reaction are greatly influenced by the presence of the CO₂ by-product. It was found out that the presence of CO₂ determines whether the reaction is first or zero order since it causes deactivation of the catalyst via inhibition. The effect of potassium carbonate (K₂CO₃) and triethylamine (TEA) as additives was investigated. A considerable solvent effect was also observed that may be explained by the variation of dispersion of the catalyst from one solvent to another.     

Editorial

Ohne Zusammenfassung     

Management of rhesus isoimmunization by preimplantation genetic diagnosis

Intracranial osteolipomas are rare lesions which occur in the region of the tuber cinereum. All cases reported to date have been incidental autopsy findings. We describe a patient who presented with a variety of neurological symptoms and had a typical osteolipoma surgically removed.     

Multisource-sputtered ErBa2Cu3O7−x films on single-crystal and buffered crystalline substrates

High-quality superconducting films of erbium-barium-copper-oxide have been produced in a multisource sputtering system on a variety of substrates, including buffered sapphire and silicon wafers as well as various single-crystal materials. Fine-grained polycrystalline films with narrow (<4 K) resistive transitions have been grown on a number of different substrates. The use of erbium in the 12–3 compound leads to improved film morphology and to more forgiving conditions for establishing of the superconducting phase. Sputtered neutral mass spectroscopy (SNMS) yields useful information about the compositional profile of the films.     

Analysis of the MSS51 region on chromosome XII of Saccharomyces cerevisiae.

We have localized gene MSS51 on chromosome XII of Saccharomyces cerevisiae between the RDN1 and CDC42 loci. 'Head to head' with MSS51 is another gene, QRI5, the function of which is unknown. However, the proximity of these genes, the structure of the intergenic region and the presence of an ABF1 binding site right in the middle of this region suggest that the MSS51 and QRI5 expressions are submitted to a common regulatory process.