**2.1.2 Development**

### **2.1.2.1 A curiosity in biological barriers: discrimination between strontium and calcium**

It is assumed axiomatically that biological organisms use Sr less effectively than Ca, which means that they discriminate against Sr in favour of Ca. This may be expressed in another manner by the concept "Strontium-Calcium Observed Ratio" (OR), the value of which is lower than 1. Comar et al. (1956) introduced the term to denote the overall discrimination observed in the movement of the two elements from one phase to another under steadystate conditions. The term OR denotes the comparative rates of Sr and Ca in balance between a sample and its precursor and is defined as:

OR= (Sr/Ca) sample/(Sr/Ca) precursor.

More precisely, the OR can be defined as the product of a number of 'discrimination factors' (DF), each of which is a measure of the extent to which the physiological process to which it refers contributes to the overall discrimination.

In this line it is shown one of the first studies which aimed to ascertain at what intestinal level the Sr/Ca discrimination takes place. Vitamin D3, 25-hydroxy-cholecalciferol (25-0H-CC) and 1,25-dihydroxy-cholecalciferol (1,25 (OH)2-CC) were administered to rats. The apparent and

Atomic Absorption Spectroscopy: Fundamentals and Applications in Medicine 9

deposited in a proportion of more than 99% and the proteins involved with albumin and the alpha2 macroglobulin (α2MG). The α2MG bound tightly to the metal is responsible for 30- 40%. The aminoacids are only responsible for about 2% of bonded Zn (Giroux & Henkin, 1972). The serum levels of Zn vary in different pathological symptomatologies and in relation to the amount of exercise. Several studies have shown these variations are related to the percentage of the element bound to albumin and another one established this relation between total serum Zn and α2MG-bound Zn, in athletes after exercise (Castellano et al., 1988). This last study was aimed at analysing the variations in the serum levels of Zn after acute and chronic overload of this element and verifying whether these variations may be correlated to changes in the percentage of the element bound to albumin, α2MG or both.

After a single intragastric administration of 0.5 mL of a solution containing 1000 ppm of Zn, the levels of this metal increased significantly (p<0.01) in serum 30 min after the beginning of the experiment, reaching maximum values at one hour and returning to normal levels 24 h later. It should be noted, however, that 8 h after administration the increases were no significant (p>0.05). The concentration of Zn bonded to albumin varied in parallel to the total serum levels of Zn. The values of bonded Zn in the globulins α2MG also varied but the

The chronic overload was performed with different groups who underwent a daily intragastric dosis of 0.5 mL of the same solution used for the acute overload. Different group of animals were sacrificed on days 7, 14, and 30 after the beginning of the experiment, with the aim of collecting values at different times of the overload. The control group and one other were used for recuperation and were kept for ten days with no treatment after day 30. Chronic overload of Zn caused significant increases in the serum levels of Zn throughout all the experiments. The highest values were found on the 14th day. The amount of Zn bonded to albumin varied in parallel with the total serum Zn; however, the concentrations of Zn bonded to globulins (α2MG) showed a significant decrease (p<0.05) on the seventh day, increasing significantly (p<0.01) on the 14th day and the 30th day and returning to normal

The results of the acute overload suggest a correlation with the proportion of element bonded to the albumin and those of the chronic overload showed a rapid response of the albumin while the increases of element bonded to the α2MG responded slowly and remained constant until the end of the experiment. However, at this time the total serum Zn

These results suggest that albumin may play a new physiological role by adjusting its

In the same line the levels and distribution of serum Cu and Zn were studied in patients diagnosed with acute myocardial infarction from the day of admission to the Cardiovascular Intensive Care Unit until the 10th day following the attack (Gómez et al., 2000). The results obtained showed that Cu increased significantly after the 5th day after the myocardial infarction, while Zn decreased significantly (p<0.01) with relation to the control

Later, the total serum Cu showed an excellent correlation with the Cu bonded to the albumin and to the globulins (ceruloplasmin), as well as with the concentration of both

group after the 1st day, the lowest values being found on the 3rd day after the attack.

values returned to basal concentrations 4 h after the beginning of the experiment.

values 10 days after Zn overload was interrupted.

and the Zn bonded to albumin decreased.

binding capacity to the serum Zn levels.

real intestinal absorption were analysed at those moments when their activity was maximum. Different concentrations of Sr were used and it was concluded that the discrimination occurred in the passive rather than in the vitamin-dependent transport (Escanero et al., 1976).
