Computer simulation of the effect of temperature on pH.

The effect of temperature on solution pH was simulated by computer (program PHTEMP). We have determined that the change in pH due to shifts in acid-base equilibria [delta pH = pH(60 degrees C) - pH(25 degrees C)] can be substantial for compounds such as aliphatic amines that have high enthalpies for acid dissociation. This is of particular significance during elevated temperature experiments in which changes in the pKa values of formulation components, and hence the solution pH, can accelerate decomposition as compared to those formulations where sensitive functionality is absent. PHTEMP afforded the following results at initial pH = 7 (25 degrees C): (a) 0.1 M triethylamine (delta H zero = 10.4 kcal/mol) delta pH approximately -0.8; (b) 0.1 M acetic acid (delta H zero = -0.1 kcal/mol) delta pH approximately 0; (c) 0.1 M sulfuric acid (delta H zero 1 = -12 kcal/mol; delta H zero 2 = -5.4 kcal/mol) delta pH approximately -0.4. Solutions of general pharmaceutical interest were also studied and included a 12-component amino acid mixture, 0.1 M glycine, and 0.1 M triethylamine in either 0.02 M citric acid or 0.05 M TRIS buffer. In each case the pH change with temperature was dependent on the concentrations of components, the enthalpies for each acid dissociation, and the starting pH. At lower pH (< 4), PHTEMP predicts that delta pH is typically smaller than at higher pH (> 9). These results are interpreted as the effect of a relative change in hydronium ion activity, delta H+/H+(initial), due to temperature-induced shifts in equilibria (acid dissociation, water autoprotolysis). This relative change must become larger as H+ decreases (pH increases). The output of PHTEMP was experimentally verified with 0.1 M glycine and with a multiple component amino acid solution. In both cases, agreement with prediction was excellent. The results of this investigation underscore the need to critically review formulation choices for both thermodynamic and traditional kinetic effects on the resulting product stability.

[Proximal trisomy 19q. Interstitial deletion and ring chromosome derived from 19q]. / Trisomie 19q proximale. Délétion interstitielle et chromosome en anneau dérivés du 19q.

A proximal 19q duplication was observed in lymphocytes of a young boy with mental retardation, dysmorphism (weight excess, macrocephaly, downward slanted palpebral fissures, hypertelorism, broad nose, typical mouth), without visceral malformation. His mother had an interstitial deletion and ring chromosome derived from 19q.

Low frequency neurons in the lateral central nucleus of the cat inferior colliculus receive their input predominantly from the medial superior olive.

When iontophoretic injections of horseradish peroxidase were made in the vicinity of inferior colliculus units in the cat responding to low sound frequencies, retrograde labelling occurred in the ipsilateral medial superior olive. Both bipolar and multipolar cells of the medial superior olive participated in this projection, and the focus of labelling shifted topographically within the olive as the injection site best frequency varied. These observations confirm previous anatomical findings and link them to the tonotopic organization of the central nucleus of the inferior colliculus. However, the fact that the medial superior olive alone provides between 50 and 98% of labelled cells in the brain stem projecting to this region of the central nucleus is an unexpected observation. This study gives further support to an hypothesis of 'core zones' within the central nucleus that receive preferentially input from specific brain stem auditory nuclei.