Carbohydrates and vaccines: from purified polysaccharides to semi-synthetic glycoconjugate vaccines

Over the last decades, capsular polysaccharides have been successfully used as antibacterial vaccines. Marketing several polysaccharide-protein conjugate vaccines filled the gap in many areas of children and infant vaccination. By facilitating access to structures of increasing complexity, recent progress in glycochemistry has enabled the design of more and more precisely defined glycoconjugate vaccines using synthetic saccharide components which mimic epitopes naturally implicated in protection. This strategy was recently validated in humans. It opens the way to new perspectives in vaccine research devoted to prophylactic and/or therapeutic applications against bacterial, fungal, parasitic or viral infections, and certain cancers.     

Evidence that the purported dopaminergic agonist (3,4-dihydroxyphenylimino)-2-imidazolidine (DPI) may reduce rat striatal dopamine turnover by an alpha 2-adrenergic mechanism

The potent alpha-adrenergic agonist DPI, which has also been claimed to be a selective dopaminergic agonist, was shown to reduce rat striatal dopamine (DA) synthesis, DA utilization and DA metabolism following intraperitoneal administration (25 mumol/kg). An analytical procedure for the determination of DPI was developed and its application showed that DPI did not penetrate into the brain in substantial amounts. The possibility of a direct stimulatory action upon striatal presynaptic DA receptors was excluded by the demonstration that DPI lacked effectiveness both in the gamma-butyrolactone model and following intrastriatal administration. The selective alpha-adrenergic agonists phenylephrine (alpha 1) and tramazoline (alpha 2) decreased and increased DA metabolism, respectively, the yohimbine-induced increase being antagonized by DPI. The carbon-bridge analogue (3,4-dihydroxybenzyl)-2-imidazoline (DHBI) had about the same activity as DPI, whereas the potential DPI metabolite (4-hydroxy-3-methoxyphenylimino)-2-imidazolidine (HMPI) was without effect upon striatal DA metabolism. The results are discussed in relation to the remarkable resemblance with the literature data concerning clonidine. It is concluded that the DPI-elicited attenuation of striatal DA turnover is, in all likelihood, the result of a stimulation of alpha 2-adrenoceptors possibly located within the central nervous system. The results cast some doubt on the designation of DPI as a selective DA-inhibitory receptor agonist.     

Comparaison de l'effet somnogène de deux médicaments,le Ro 5-4200 et le Nitrazepam

Résumé Au cours d'une étude comparative entre l'action de 2 mg de Ro 5-4200 et de 10 mg de Nitrazepam sur les durées d'endormissement et de sommeil, 35 patients ont été observés. L'efficacité de ces deux substances dans un rapport de doses de 1 à 5 est comparable sur les deux variables observées. Toutefois, si le médicament est pris juste au moment du coucher, le Ro 5-4200 induit d'une manière significative un peu plus rapidement le sommeil que le Nitrazepam. En considérant les nuits dans leur ensemble sans tenir compte des sujets, aucune différence significative n'a été observée pour l'un ou l'autre des médicaments, en fonction de la régularité ou de l'irrégularité dans le moment de la prise. L'induction au sommeil dans ces conditions est donc peu brutale. Enfin, il existe une corrélation négative entre la durée d'endormissement et la durée de sommeil. En d'autres termes, ce sont les malades qui s'endorment le plus rapidement qui dorment le plus longtemps. Cette corrélation est significativement plus grande avec le Ro 5-4200.Nous remercions la Maison Hoffmann-La Roche (Bâle), qui nous a aimablement fourni le Ro 5-4200.     

Halogens: discoveries of pharmacists

The discovery of four halogens is due to pharmacists. Chlorine was isolated by Carl Wilhem Scheele, a Swedish who was first an assistant to a pharmacist, then a pharmacist himself. Bernard Courtois, a pharmacist under the First Empire, the son of a saltpetre worker isolated iodine in I811, after a modification of the ancestral production protocol of potassium nitrate, which is the major component of the gunpowder: he replaced wood ashes by varech ashes which are less expensive. Antoine Jer?me Balard was still an assistant in chemistry and physics when he discovered bromine in the residues of the salt marshes. He became soon after a pharmacist and started a famous career as then he became Professor in the College de France and General Inspector of Higher Education. The last halogen: fluorine was isolated by Henri Moissan who received the Nobel Prize of Chemistry. The discovery will be the subject of our next communication.     

Evaluation of the effects of electric and magnetic fields in humans

During the twentieth century, environmental exposure to electromagnetic fields generated by human activity has increased regularly, at the same time as the quest for electrical energy. Therefore we are all exposed to a complex set of electric and magnetic fields of weak intensity. The levels of exposure of the general population range from 5 to 50 V/m for electric fields and from 0.01 to 0.2 micro T for magnetic fields. Fields in cause are essentially those associated to the use of the electric current (extremely low frequency, ELF: 50 Hz in France, 60 Hz in the United States) and those related to the use of cell phones (radio frequency: 900 and 1,800 MHz). The question of the possible risk on health by exposure to electric and/or magnetic fields became a concern to scientists and is now an important public debate. A number of expertises, led in particular by the WHO, leaning on the careful inspection of scientific publications from numerous countries, conclude that current data do not allow to assert the existence of sanitary effects; however our knowledge of the biologic effects of electromagnetic fields still contains certain gaps which should be filled. Indeed, the numerous epidemiological studies relative to the occurrence of cancer by exposure to electromagnetic fields are conflicting. In every case the increase of the risk, when described, is always weak. The measure of the Relative Risk (RR) which establishes the relation is approximately 2-3. At present, some data concerning the risk of childhood leukemia in the event of exposure of ELF generated in the home indicate that this risk can exist when children are chronically exposed to more than 0.4 micro T (the relative risk is in the order of 2). In the field of radio frequencies, the increasing use of cell phones (38 million users in France) and their antennae - basis are another subject of concern for the effects on health they are susceptible to produce. Large-scale studies, implying numerous countries, carried on at present within the framework of the WHO should bring elements of answer to the unresolved questions.     

Affective disorders and biological rhythms

Disruptions of circadian rhythms are described in affective disorders, including unipolar and bipolar disorder, but also seasonal affective disorder. Sleep-wake and hormone circadian rhythms are among the most quoted examples. Depression could be conceptualized as a desynchronization between the endogenous circadian pacemaker and the exogenous stimuli, such as sunlight and social rhythms. Accordingly, Clock genes have been studied and the literature suggests that variants in these genes confer a higher risk of relapse, more sleep disturbances associated with depression, as well as incomplete treatment response. Most of therapeutic interventions in depression have an impact on biological rhythms. Some of them exclusively act via a biological pathway, such as sleep deprivation or light therapy. Some psychosocial interventions are specifically focusing on social rhythms, particularly in bipolar disorder, in which the promotion of stabilization is emphasized. Finally, all antidepressant medications could improve biological rhythms, but some new agents are now totally focusing this novel approach for the treatment of depression.