Interactions related to trace elements in parenteral nutrition.

Trace elements (TE) are now commonly added into the nutritive admixtures used in total parenteral nutrition (TPN) to prevent deficiencies which can be observed in patients undergoing long-term intravenous feeding. Although the needs in TE are not exactly known during a TPN, some of them must be considered as essential according to the results of studies dealing with general nutritional deficiencies. Among essential TE copper, iron and zinc are found at relatively high levels in organism. Chromium, manganese and selenium are also very important even though they are present at lower levels. In the case of a parenteral nutrition, the composition of the mixture is precisely defined and both digestion and absorption steps are shunted. Nevertheless, beneficial and/or negative physicochemical and metabolic interactions can occur between TE and the other nutrients. These interactions must be studied and taken into account because they can modify the bioavailability of the trace elements. In this article, our aim is to review the main recent bodies of knowledge which could be helpful to understand and prevent nutritional problems linked to these interactions during parenteral nutrition.

Effect of taurine, L-glutamine and L-histidine addition in an amino acid glucose solution on the cellular bioavailability of zinc.

Radioactive zinc was used to study the effect of a binary parenteral nutrient solution, composed of amino acids and glucose, on zinc uptake by fibroblasts. The influence of addition of taurine, L-glutamine and of the increase in L-histidine content of the admixture was assessed. The pure mixture was highly toxic for cells and so it was diluted 1/5 in tyrode buffer with 2% albumin. As compared with cells incubated in the buffer containing albumin, zinc absorption was significantly higher (P < 0.05) in the presence of the amino acids of the mixture. Amino acids thus increased bioavailability by displacing zinc bound to albumin. When the histidine concentration in the nutrient medium (4.2 mM) was doubled, inhibition was noted after 30 min of incubation and zinc uptake thereafter remained comparable to that in histidine-free medium. The addition of glutamine (4.2 mM), usually not present in binary mixtures, resulted in significant differences as compared with glutamine-free control medium. Taurine (0.8 mM), led to a constant increase in zinc uptake by fibroblasts as compared with that obtained with taurine-free mixture. However, ultrafiltration showed that taurine was not able to displace zinc from albumin.

Particle contamination in a ternary nutritional admixture.

During total parenteral nutrition, the intravenous infusion of large volumes over a prolonged period of time appears to involve risks of particle contamination for the patients. The aim of this work is to number, measure, and characterize inert particles in a standard ternary mixture prepared by sterile transfer technique. The distribution of particles is studied in each component of the admixture and in the final preparation using two different methods: the Coulter counter and an optical microscopic numbering after filtration. The nature and the origin of particles are determined by the use of scanning electron microscopy (SEM) coupled with a photon X spectrometer.

Influence of copper, iron, and zinc on the physicochemical properties of parenteral admixture.

A parenteral admixture composed of 25% of 20% Intralipid, 25% of Azonutril 25, 37.5% of 30% Glucose and 12.5% of 50% Glucose was supplemented with copper, iron and zinc in the organic (gluconate) or inorganic (chloride) form at the following usual final concentrations: copper 0.24 mg/L, iron 0.50 mg/L, zinc 2.00 mg/L. The mixture was stored at 4 degrees C and at 25 degrees C for 24, 48, and 72 hours, and for one week. Determination of the pH indicated good stability of the mixture containing the trace elements in the gluconate form. A significant decrease in the pH of the mixture containing the trace elements as chlorides was noted after one week of storage at both temperatures. Particle size analysis revealed no significant variations between the two formulations after one week of storage. Flocculation kinetics confirmed the results obtained with the other two methods used to determine physicochemical stability. In addition, the kinetics indicated that the possibilities of coalescence processes are highly reduced in all cases. It may be concluded that the two type of mixtures remain stable for Seven days at 4 degrees C and 25 degrees C. However, mixtures containing trace elements in gluconate form should be chosen in cases of longer storage.

[Pharmaceutical engineering in drug formulation]. / Le génie pharmaceutique au service de la formulation des médicaments.

The industrial pharmacist, a "pharmaceutical engineer"? The prospect is tempting if only beneficial to drug quality. The Pharmaceutical Engineering comes from Chemical Engineering and Engineer sciences and allows the pharmacist to achieve his aim. We define here the basis of this recent concept, its intervention and interest in the pharmaceutical sciences, more particularly in formulation.

Red dye No. 2 and the red pigment carmine enhance aryl hydrocarbon hydroxylase and guanylate cyclase activities.

The food coloring amaranth (F, D and C red No. 2) and the red pigment carmine, but not erythrosine (F, D and C red No. 3), caused a twofold enhancement of two enzymes (aryl hydrocarbon hydroxylase and guanylate cyclase) that have been linked with chemical carcinogenesis. Dose response relationships revealed that carmine enhanced both enzymes to near maximal levels at concentrations as low as 1 to 10 nM while amaranth needed a concentration of 100 nM to cause a maximal enhancement. These data suggest that amaranth and carmine mimic the effects of some chemical carcinogens at the cellular level, but erythrosine does not mimic any of these effects.

Gibberellic acid, a plant growth hormone, enhances mammalian guanylate cyclase activity.

In vivo injections of gibberellic acid, a potent plant growth hormone, are known to increase the growth of animals as well as plants. Investigation into gibberellic acid's growth promoting mechanism in animals at the cellular level focused on guanylate cyclase (E.C.4.6.1.2.), an enzyme known to be associated with growth. Gibberellic acid enhanced the activity of rat lung guanylate cyclase over a concentration range of .00001 mM to 1 mM with no stimulation being observed at .000001 mM. Varying the concentration of the guanylate cyclase co-factor manganese had no effect on gibberellic acid's enhancement of guanylate cyclase activity. Since human and rat growth hormones also enhance guanylate cyclase activity, it appears that at cellular level the mechanism of action of growth promoting hormones may include a common process that involves enhancement of guanylate cyclase activity.