Investigating cationic and zwitterionic successive multiple ionic-polymer layer coatings for protein separation by capillary electrophoresis.

Successive multiple ionic-polymer layers (SMILs) have long since proved their worth in capillary electrophoresis as they ensure stable electroosmotic flow (EOF) and relatively high separation efficiency. Recently, we demonstrated that plotting the plate height (H) against the solute migration velocity (u) enabled a reliable quantitative evaluation of the coating performances in terms of separation efficiency. In this work, various physicochemical and chemical parameters of the SMIL coating were studied and optimized in order to decrease the slope of the ascending part of the H vs u curve, which is known to be controlled by the homogeneity in charge of the coating surface and by the possible residual solute adsorption onto the coating surface. SMILs based on poly(diallyldimethylammonium chloride) (PDADMAC) and poly(sodium styrene sulfonate) (PSS) were formed and the effect of each polyelectrolyte molar mass and of the number of polyelectrolyte layers (up to 21 layers) was studied. The use of polyethylene imine as an anchoring first layer was considered. More polyelectrolyte couples based on PDADMAC, polybrene, PSS, poly(vinyl sulfate), and poly(acrylic acid) were tested. Finally, zwitterionic polymers based on the poly(α-l-lysine) scaffold were synthesized and used as the last layer of SMILs, illustrating their ability to finetune the EOF, while maintaining good separation efficiency.

Pharmacokinetics of THC in brain and testis, male gametotoxicity and premature apoptosis of spermatozoa.

An earlier report described the pharmacokinetics of delta-9 THC and the resulting brain function responses. In the present studies the pharmacokinetics of THC in plasma, brain and testis were related to impairment of spermatogenesis. THC- containing preparations, whatever their route of administration, were associated with the induction of gametotoxicity in all species studied including man. The pharmacokinetics and molecular binding of THC is similar in all experimental models. Concentrations of THC in plasma, fat, testis, brain and spleen were measured following administration of tracer amounts of C(14) delta-8 THC labelled at the C(11) position. Rats were administered 2 microCi of the tracer by i.m. injection, and killed at regular intervals after a single or multiple dose of the label. After a single dose, the maximal radioactivity was reached in brain after 2 and 4 h and amounted to 0.06% of the administered dose. In the testis, the concentration did not exceed 0.023% of the administered dose. In epididymal fat, the total radioactivity after 4 h was five times higher than in the brain and after 24 h it was eight times greater. After multiple injections of C(14) THC, concentrations of the drug remained low in the plasma, brain and testis not exceeding 2-7 ng/g, but the epididymal fat tracer concentration was 40-80 times higher. Plasma concentrations of C(14) THC were of the same magnitude as those measured by GCMS in the plasma of men exposed to marihuana smoke or THC, and in whom alterations of spermatogenesis were observed. In these studies, plasma THC ranged from 9.5x10(12) M to 2.4x10(14) M. These data illustrate the efficiency of the blood-brain barrier and blood-testicular barrier in limiting the storage of THC into brain and testis. During chronic exposure to THC the pharmacokinetic molecular mechanisms which limit the storage of THC in the brain and testis are not sufficient to prevent a persistent deregulation of membrane signalling and the induction of functional and morphological changes which reflect a premature apoptosis of spermatogenic cells. Long term, longitudinal epidemiological studies have reported decreased spermatogenesis in healthy, fertile adult males. But no study has been initiated to relate the oligospermia of this population to the consumption of widely used psychoactive drugs.