J. G. March

Variation of InsP4,InsP5 and InsP6 levels in tissues and biological fluids depending on dietary phytate

Due to the increasing interest of InsP(6) on human health, the aim of this paper is to compare the levels of highly phosphorilated inositols (InsP(4), InsP(5) and InsP(6)) in organs and biological fluids of rats and to study the influence of the presence and absence of InsP(6) in diets. Thus, for this purpose, the variation of InsP(4), InsP(5) and InsP(6) levels in organs and biological fluids of rats submitted to two different diets were studied. In the AIN-76A diet no InsP(6) was present, yet the other was a 1% InsP(6) modified diet (AIN-76A + 1% InsP(6)). The highest InsP(4), InsP(5) and InsP(6) levels were found to be 10-fold superior in the brain than those found in the kidney. When the InsP(6) was eliminated from the diet, the InsP(6) levels decreased dramatically (97.2% in kidney, 89.8% in brain, 100% in bone, 90.5% in plasma and 98.1% in urine), the InsP(5) levels showed an important decrease (61.2% in kidney, 45.5% in brain, 28.1% in bone, 30% in plasma and 88.6% in urine) and the InsP(4) levels in organs only changed slightly. From these results, it can be deduced that the majority of InsP(6) present in the organism is of dietary origin and its endogenous synthesis is not important. According to the results, it can be evidenced that the endogenous synthesis of InsP(5) can occur, besides InsP(6) can be transformed by enzymatic dephosphorilation in InsP(5).

Inositol hexakisphosphate in urine: the relationship between oral intake and urinary excretion

Objective To study the relationship between the oral intake of inositol hexakisphosphate (InsP6, phytic acid, an inhibitor of urinary crystallization) and its urinary excretion, to establish their possible mutual influence.

Urolithiasis and Phytotherapy

The effects of seven plants with suspected application to prevent and treat stone kidney formation (Verbena officinalis, Lithospermum officinale, Taraxacum officinale, Equisetum arvense. Arctostaphylos uva-ursi, Arctium lappa andSilene saxifraga) have been studied using female Wistar rats. Variations of the main urolithiasis risk factors (citraturia, calciuria, phosphaturia, pH and diuresis) have been evaluated. It can be concluded that beneficial effects caused by these herb infusions on urolithiasis can be attributed to some disinfectant action, and tentatively to the presence of saponins. Specifically, some solvent action can be postulated with respect to uric stones or heterogeneous uric nucleus, due to the basifying capacity of some herb infusions. Nevertheless, for all the mentioned beneficial effects, more effective and equally innocuous substances are well known.

Phosphates precipitating from artificial urine and fine structure of phosphate renal calculi

Phosphates precipitating from artificial urine in the pH range 6-8 were identified using X-ray diffraction, chemical analysis and scanning electron microscopy. The influence of magnesium and citrate on phases precipitating from urine was established. From urine containing a normal quantity of magnesium (around 70 ppm), brushite accompanied by hydroxyapatite (HAP) precipitated at pH < or = 7.0 and struvite with HAP at pH > 7.0. HAP was formed exclusively from magnesium deficient urine at pH 7.0. Newberyite, octacalcium phosphate and whitlockite were not identified. The chemical and phase composition and inner fine structure of 14 phosphate calculi were studied. Three types of stones were distinguished based on their magnesium content: (i) stones rich in magnesium composed of struvite, hydroxyapatite and abundant organic matter, (ii) stones with low magnesium content constituted by calcium deficient hydroxyapatite, up to 5% of struvite, considerable amount of organic matter and occasionally brushite, and (iii) calculi without magnesium consisting of brushite, hydroxyapatite and little organic matter. Conditions prevaling during stone-formation assessed for each type of stone were confirmed by corresponding urinary biochemical data and corroborate the in vitro studies of phosphates precipitation.

Determination of pyrophosphate in renal calculi and urine by means of an enzymatic method.

An enzymatic method for the determination of pyrophosphate which has been applied to renal calculi is described. The method involves the preconcentration of pyrophosphate using anionic exchange resin and development of the enzymatic reactions with the pyrophosphate retained on the resin. The study of calculi treatment according to calculi composition is also reported. The pyrophosphate content was dependent on the calculi composition. The highest amount of pyrophosphate was found in hydroxyapatite calculi (of the order of 10 microg/g), struvite and oxalate calculi showed a lower amount (the order was 2.5 and 4.5 microg/g, respectively) and was not detected in uric acid and cystine stones. The method was also successfully applied to the determination of pyrophosphate in human urine. For urinary pyrophosphate determination, a modification based on a clean-up of urine using activated carbon has been proposed. Pyrophosphate in human urine was of the order of 4 mg l(-1).

Dietary phytate and mineral bioavailability

The relation between the dietary phytate (InsP6), mineral status and InsP6 levels in the organism, using three controlled diets (AIN-76A, AIN-76A + 1% phytate, AIN-76A + 6% carob seed germ), are studied. AIN-76A is a purified diet in which InsP6 is practically absent. No important or significant differences in the mineral status (Zn, Cu, Fe) of blood, kidneys, liver, brain and bone, were observed, except iron in the brain. Thus, the amounts of iron found in the brain of rats fed AIN-76A + 1% InsP6 were significantly inferior to those found in rats fed AIN-76A diet. The amounts of InsP6 found in organs of rats fed AIN-76A diet became very low or even undetectable while the ones found in rats fed diets that contained 1% and 0.12% (AIN-76A + 6% carob seed germ) InsP6, were considerably higher and similar. Moreover the majority of rats fed AIN-76A diet exhibited calcifications at the corticomedullary junctions, whereas no calcifications were detected in rats fed the other two diets. From these results, it can be deduced that there was no important adverse effects on mineral status as a consequence of the presence of InsP6 in the studied diets. Besides, considering that a 0.12% InsP6 contained in the AIN-76A purified diet through the addition of a 6% of carob seed germ to this diet, produced the same beneficial effects as the direct addition of a 1% of InsP6 and no negative effects on mineral status was observed, it can be concluded that the value of the presence of InsP6 at adequate amounts in the diet is remarkable and must be favourably considered.

Glycosaminoglycans, uric acid and calcium oxalate urolithiasis

SummaryThe interaction between calcium and glycosaminoglycans (GAGs) was studied using a calcium ion-selective electrode. The Ca-binding capacity of GAGs involved 16% of total calcium in the presence of chondroitin sulphate and 28% in the presence of pentosan polysulphate. The action of GAGs on the nucleation of uric acid and sodium urate was examined and inhibitory effects were observed. The action of uric acid as a heterogeneous nucleant of calcium oxalate was studied, and considerable promotion of the heterogeneous nucleation of calcium oxalate by uric acid was found, which could be inhibited by the action of GAGs. From these summarised in vitro results, we conclude that uric can constitute an important risk factor for calcium oxalate urolithiasis through heterogeneous nucleation and the GAGs can play an important role as preventive agents.

The crystallization of calcium oxalate in the presence of aminoacids

Abstract The kinetics of crystal growth of calcium oxalate seed crystals were investigated conductimetrically and potentiometrically at several ionic strengths, in stable calcium oxalate supersatured solutions. An apparent rate order of 2 at all the ionic strengths tested suggested a spiral growth mechanism. The presence of aspartic acid in the supersaturated solution inhibited crystal growth. Application to a kinetic Langmuir-type model suggested that adsorption of the aminoacid at the active growth sites is the cause of the reduction in the crystal growth rates. Adsorption studies revealed that inhibition of crystal growth was enhanced at lower solution ionic strengths. This ionic strength dependence indicated that the calcium oxalate-aminoacid interaction is mainly electrostatic in its nature.

Epidemiology of Urinary Stone Disease in the Balearic Islands Community

In a survey conducted on 1500 individuals, an overall prevalence of 14.3% for the year 1990 was found for urinary stone disease in the Balearic Islands. The prevalence showed higher figures for people living in rural areas than for those living in cities, and this could be correlated with traditional living habits such as traditional Balearic diet. Finally, a surprising fact is that only 54% had consulted a urologist as outpatients and the rare occasion at which the calculi were analyzed (15.1%).

Vitamin A and urolithiasis

The effects of vitamin A deficiency on urolithiasis were investigated in male rats. A vitamin A-deficient diet caused important changes in the composition of the urine of the treated rats when compared with controls. One of the main effects was a decrease in the concentration of urinary glycosaminoglycans and zinc in the rats receiving the vitamin A-deficient diet. Significant differences were also found in plasma vitamin E and in the relation of vit E/vit A between treated and control groups but, in general, with no important differences in vitamin A. Nevertheless, significant differences in kidney content of vitamin A were observed between both groups. On the other hand, lesions of the cuboidal epithelium that covers the papillae in rats treated with the vitamin A-deficient diet were severe when compared with controls. The vitamin A and E plasma levels in urolithiasic humans were also investigated and compared with those found in a control group. No significant differences were observed in plasma vitamin A levels; nevertheless a significant increase in vitamin E and in the vit E/vit A ratio was clearly observed. These results could be related to a possible deficit of vitamin A in kidneys of stone formers, this being one of the diverse factors that can contribute to urolith development. Moreover, the deficit of important urinary crystallization inhibitors normally found in stone-formers, such as pyrophosphate and phytate, can also be related to the presence of low levels of renal vitamin A which prevents the enzymatic degradation of such inhibitors.