Mesencephalic microinjections of neurotensin-(1-13) and its C-terminal fragment, neurotensin-(8-13), potentiate brain stimulation reward

Using the curve shift method, we assessed the effects of ventromedial mesencephalic tegmental (VMT) microinjections of an equimolar concentration of neurotensin-(1-13) (NT-(1-13)) and of its C-terminal fragment, neurotensin-(8-13) (NT-(8-13)), on operant responding for rewarding electrical stimulation of the caudal mesencephalic central gray. The effects of NT-(1-13) and NT-(8-13) on brain stimulation reward (BSR) were also compared to those of systemically administered quinpirole (0.1 and 0.2 mg/kg, s.c.), a direct dopamine agonist, and GBR-12909 (10 and 20 mg/kg, i.p.), a selective dopamine uptake blocker. At the concentration injected, NT-(8-13) was as effective as NT-(1-13) at facilitating BSR, producing significant leftward shifts of the function relating the rate of responding to the stimulation frequency (R/F function); neither form of the peptide was effective when injected in regions dorsal to the VMT. Similarly, GBR-12909 produced a parallel leftward shift of the R/F function, but, unlike NT-(1-13), also significantly increased the asymptotic rates of responding. In contrast, the high dose of quinpirole produced non-parallel leftward shifts of the R/F function and suppressed the asymptote. The similarity between the effects of neurotensin and GBR-12909 on one hand, and the differences between those of neurotensin and quinpirole on the other, suggest that activation VMT neurotensin receptors potentiate BSR by enhancing increases in dopamine neurotransmission that are contingent upon operant responding or rewarding brain stimulation, or both.(ABSTRACT TRUNCATED AT 250 WORDS)     

B. F. Skinner: Au-delá de la controverse.

Discusses controversies surrounding the work of B. F. Skinner's influence on various theories of human and animal behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Organization and results of drug vigilance in France

Pharmacovigilance represents all methods of detection, assessment, information and prevention of adverse drug reactions (ADRs). It mainly involves the post-marketing phase because of the low probability of detecting all possible adverse effects of a drug during pre-marketing development. The most widely used method for pharmacovigilance is spontaneous reporting which is an excellent signal generator but precludes satisfactory calculation of incidence rates. The French Pharmacovigilance System has been set up in 1973; reporting of ADRs has been made mandatory in 1984 for prescribers. This system consists in a network of 30 regional centres under supervision of a coordinating committee at the French Drug Agency. The number of ADR cases received, assessed and recorded by the regional centres is around 10,000 per year; a similar number of cases are reported to the Drug Agency by the pharmaceutical industry. Moreover, Regional Centres work as Drug Information Centres answering more than 23,000 inquiries per year.     

Binding of tissue plasminogen activator to endothelial cells. The effect on functional properties. Localization of a ligand in the B-chain of tPA

The binding of 125I-labelled tissue plasminogen activator (tPA), the tPA A- or B-chain to endothelial cells (EC) were studied in suspensions of cultured human umbilical vein EC (HUVEC) or immortalized microvascular EC (HMEC). By determinations of the concentration-dependent binding it was shown that both the A-chain and the B-chain, which were isolated after partial reduction of two-chain tPA, contain ligands for binding to EC. The affinity for the B-chain was much higher than for the A-chain according to Scatchard analysis (Kd 24 and 515 nM, respectively), whereas the number of binding sites was higher for the A-chain than for the B-chain (Bmax 8 x 10(5) and 1.2 x 10(5), respectively). There were no cross interactions between the A- and B-chains and their binding sites. The binding of tPA to EC induced an almost 100-fold increase of the activation rate when compared to the same amount of enzyme in free solution, which in contrast to the fibrin-induced stimulation was not inhibited by antibodies against fibrin. The enzymatic activity of the B-chain was much less affected by the association to the cells. Both tPA and the tPA B-chain were largely protected against inhibition by an excess plasminogen activator type-1 (PAI-1) when bound to EC, whereas the same amount of free tPA was totally inactivated. The competition studies strongly indicated that an N-terminal segment in the B-chain, AKHRRSPGER, may be the ligand part of the B-chain. It is interesting to note that this polypeptide segment also participates in a binding site for PAI-1, necessary for effective inhibition. This implies a possible competition between PAI-1 and a tPA-receptor for binding of tPA. High molecular weight urokinase had no quenching effect on the binding of the B-chain to EC.     

Anodic oxidation of mecoprop herbicide at lead dioxide

The electrochemical oxidation of an aqueous solution containing mecoprop (2-(2-methyl-4-chlorophenoxy)propionic acid) has been studied at PbO₂ anodes by cyclic voltammetry and bulk electrolysis. The influence of current density, hydrodynamic conditions, temperature and pH on the degradation rate and current efficiency is reported. The results obtained show that the use of PbO₂ leads to total mineralization of mecoprop due to the production of oxidant hydroxyl radical electrogenerated from water discharge. The current efficiency for the electro-oxidation of mecoprop is enhanced by low current density, high recycle flow-rates and high temperature. In contrast, the pH effect was not significant. It has also been observed that mecoprop decay kinetics follows a pseudo-first-order reaction and the rate constant increases with rising current density.