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Biomedical subjects

N Krari

Publications and source records attributed to N Krari.

17 recordsLinked to original sources

[Lead blood levels in children under 6 years of age in the Mans region].

OBJECTIVES: High lead levels in children can have a deleterious effect on intellectual development. We assessed blood lead levels in children in the Le Mans region. METHODS: Children aged between 6 months and 6 years were included in the study. Inclusion criteria were health status requiring a blood sample and amount of blood available after ordered tests sufficient for lead blood analysis. The study group included 365 children. RESULTS: Mean blood level in the 365 children was 37.2 +/- 20.6 micrograms/l. Six of the children had blood levels greater than 100 mu/l. None of the children had a level over 200 micrograms/l. Location of the home or date of construction of the home were not significantly correlated to blood lead levels, however blood lead levels were higher in children with neurological or behavioral disorders. This observation was made in a limited number of children. CONCLUSION: The risk of excessively high blood lead levels in children under 6 years of age is low in the Le Mans region. There is however a risk when old houses are renovated or in children with neurological or behavior disorders.

Age Factors↗

Enhancement of aluminum digestive absorption by fluoride in rats.

Aluminum, responsible of dialysis encephalopathy, is suspected to be involved in other neurological disorders such as Alzheimer disease. Absorption of aluminum from the digestive tract can be enhanced by the concommittant intake of substances such as citrate. We studied in rats and mice the interactions between fluoride and aluminum for their digestive absorption and showed that fluoride increased the levels of aluminum in plasma as much as citrate whereas aluminum decreased the absorption of fluoride. This result could be the consequence of the high affinity between aluminum and fluoride which form complexes able to increase the absorption of aluminum and to decrease the absorption of fluoride.

Aluminum↗

Enhancement of bismuth toxicity by l-cysteine.

Bismuth-induced encephalopathies observed in France about twenty years ago have never received convincing explanation. In previous papers we have shown in animal experiments that L-cysteine enhanced Bi absorption without leading to encephalopathies. in this paper we have studied in greater detail the toxicity and the pharmacokinetics of Bi, and L-cysteine, given by intraperitoneal route to mice, singly and simultaneously as a Bi-L-cysteine complex. Bismuth and L-cysteine, were nontoxic singly since their LD50 were higher than 15 mmol/kg, but were toxic (LD50 = 0.3 mmol/kg) when they were given as a complex. The complex was about 50 times more toxic than the separate products. The changes in the levels of Bi and L-cysteine in blood versus time after the injection of the Bi-L-cysteine complex suggests that the complex entered into the blood under a non-dissociated form but just afterwards the complex dissociated and the levels of Bi decreased rapidly whereas the levels of L-cysteine remained high. The concentrations of Bi in tissues, blood, brain, kidney and liver were higher when it was given as the Bi-L-cysteine complex than alone. But the increase of the levels of Bi in tissues induced by L-cysteine was not sufficient to explain the 50 fold increase of the toxicity of the complex in comparison with Bi and L-cysteine given alone. Since the increase of the levels of Bi induced by L-cysteine was not sufficient to explain the increase of the toxicity of the complex, another explanation is required. We suggest that this increase results from the stimulation of peroxidation by bismuth and L-cysteine, as already observed for iron and L-cysteine. Other experiments are needed to verify the validity of this hypothesis.

Animals↗

Use of plasma iodine assay for diagnosing thyroid disorders.

AIMS: To examine the advantage of systematic plasma iodine assays in establishing the thyroid function of patients with thyroid disorders. METHODS: Iodine was determined by inductively coupled plasma mass spectrometry (ICPMS) in the plasma of 799 patients consulting for possible thyroid disorders, indicated by FT4 and TSH assays. RESULTS: Plasma iodine was below 40 micrograms/l in 57 (7%) patients, most of whom had hypothyroidism; 40-80 micrograms/l in 439 (55%) patients, most of whom had normal thyroid hormone function; 80-250 micrograms/l in 240 (30%) patients, most of whom had hyperthyroidism; and above 250 micrograms/l in 63 (8%) patients, almost all of whom had iodine overload caused by iodinated drugs, particularly amiodarone, resulting in euthyroidism (24%), hyperthyroidism (36%), and hypothyroidism (16%). Sixty five (7%) had been treated with amiodarone and 27 (3%) with other iodinated drugs. More than 10% of patients with thyroid disorders therefore had an iodine overload. CONCLUSIONS: The determination of total plasma iodine using the simple, accurate ICPMS technique, should be carried out in patients consulting for thyroid disorders, particularly for the detection of an iodine overload.

Adult↗

Bromine and thyroid hormone activity.

AIMS: To examine the possible consequences of high plasma concentrations of bromine on thyroid hormone. METHODS: Bromine was measured by inductively coupled plasma mass spectrometry in the plasma of 799 patients consulting for thyroid disorders. Because the mean (SD) bromine concentration in the plasma of healthy subjects is 4 (1) mg/l, concentrations above 6 mg/l were regarded as outside the normal range. Bromine, free thyroxine (FT4), and thyroid stimulating hormone (TSH) values were compared. RESULTS: The percentage of patients with normal, low, and high FT4 and TSH plasma activities, measured separately, did not differ between patients with low and high bromine concentrations. The percentage of patients with high TSH but normal FT4 values was significantly higher in the group with bromine values of more than 6 mg/l than in the group with bromine concentrations below this (p < 0.02). CONCLUSION: An increase in plasma bromine could potentiate an increase in plasma TSH concentration, probably as a consequence of a minor inhibitory effect on thyroid activity.

Bromine↗

Diethyldithiocarbamate and brain copper.

To test the hypothesis that the increase of copper concentration in brain after diethyldithiocarbamate (DEDTC) administration was due to the formation of a DEDTC-copper complex, able to cross the blood-brain barrier, we compared in rats the effects on brain copper of DEDTC given alone, in combination with copper or as a copper-DEDTC complex. The daily administration for three weeks of DEDTC alone, of DEDTC with copper and DEDTC-copper complex gave the same increase of the level of copper in brain. The time course effects of a single administration of DEDTC and of the DEDTC-copper complex were approximately the same: after a delay of about 24 h, there was an increase in brain copper concentrations which persisted for at least three days. This delayed effect explains discrepancies found in the literature concerning changes of copper in brain after a single administration of DEDTC according to the time interval between administration and tissue sampling. The results show that the additional copper does not increase the effect of DEDTC and that the formation of a DEDTC-copper lipophilic complex which could cross the blood-brain barrier is probably not the mechanism responsible for the increase of brain copper induced by DEDTC. Mechanisms other than direct copper chelation may be involved.

Administration, Oral↗

Altered element concentrations in tissues of Dahl salt-sensitive rats.

It is recognized that the development of hypertension in Dahl salt-sensitive (DS) rats as compared to Dahl salt-resistant (DR) rats is dependent on the addition of a high percentage of sodium chloride, often 8% to the diet. In this work, blood systolic pressure and the concentrations of many elements in different tissues of DS and DR rats were measured. However, to distinguish the modifications linked to the strain from the modifications owing to excess of sodium intake, no additional Na was included in the diet in all our experiments. Without any addition of sodium chloride to the diet, a statistically significant increase of the systolic blood pressure of DS rats (152 +/- 10 mmHg) in comparison to DR rats (131 +/- 3 mmHg) was observed. The analysis of the concentrations of many elements in different tissues showed no major modifications of sodium concentrations in DS rats as compared to DR rats, but a decrease of calcium in plasma (-9%), brain (-20%), and heart (-7%) and of magnesium in plasma (-13%), kidney (-11%), and bone (-7%). In conclusion, an increased intake of Na is not necessary to obtain a higher systolic blood pressure in DS rats compared to DR rats. Since we did not find noticeable modifications of Na concentration in tissues but modifications of Ca and Mg, we suggest that an alteration of the homeostasis of these two elements may be involved in the development of the hypertension in DS rats.

Animals↗

Effects of three chelating agents, EDTA, NTA, and TPP, on the concentration of elements in rat tissues.

Ethylene diamine tetraacetic acid (EDTA), nitrilotriacetic acid (NTA), and tripolyphosphate (TPP) sodium salts were given orally to rats at the dose of 1 mmol/kg/d for 35 d. The concentrations of Na, K, Ca, Mg, P, S, Fe, Sr, Cu, and Zn were determined in blood, plasma, brain, heart, muscle, liver, kidney, duodenum, and bone of control rats and of the rats receiving EDTA, NTA, and TPP. The main effect induced by EDTA, NTA, and TPP was a decrease of the concentrations of several elements Ca, Mg, Fe, P in the duodenum. Otherwise, EDTA induced an increase of Zn in the kidney (+ 20%), NTA, an increase of Fe in liver (+ 29%), and particularly an increase of Zn in bone (+ 44%). TPP induced a slight decrease of Zn and Cu in liver. In conclusion, EDTA, NTA, and TPP taken orally at the dose of 1 mmol/kg/d for 35 d induced moderate changes of the concentrations of some elements in rat tissues, but without signs of toxicity.

Administration, Oral↗

Diethyldithiocarbamate, copper and neurological disorders.

Diethyldithiocarbamate (DEDTC) given orally to rats without any addition of copper considerably increased the concentration of Cu in the brain without any change in the other tested tissues. Cysteine, comparatively studied, did not induce any change in the brain Cu level. Based on these findings and the literature data concerning DEDTC effects in animal and human, we put forward the hypothesis that the main effect of DEDTC is to provoke in the brain not a deficiency but an excess of Cu liberated from the lipophilic complex Cu-DEDTC. Cu is then engaged in an oscillatory oxido reduction giving a Cu++ cation radical able to induce deleterious effects on tissues in a similar way as paraquat. The practical consequences of this hypothesis are considered.

Administration, Oral↗

Effects of some chelating agents on bismuth absorption in the rat.

Bismuth encephalopathies appeared in the mid-seventies in France and concerned about 1,000 people and led to a fatal outcome in 70 cases. Responsibility of Bi was clearly confirmed by the disappearance of the intoxication after prescription of drugs containing Bi had been more tightly regulated. Since the implication of a substance increasing the intestinal absorption of Bi has been suspected, we studied the concentrations of Bi in the tissues of rats who had been treated with bismuth nitrate basic 400 mg/kg per d for one month with and without an intake of a chelating agent added to the drinking water at a concentration of 10 mmol/l. The chelating agents tested were ethylenediaminetetraacetic acid (EDTA), nitriloacetic acid (NTA) and tripolyphosphate (TPP), cysteine and diethyldithiocarbamate (DEDTC). Cysteine and DEDTC gave the highest increase of Bi in tissues but with a wide dispersion of levels. However, even in the rats with the highest levels of Bi, there were no behavioral problems. EDTA induced an increase of Bi in kidney, brain and bone and NTA in kidney but there was no obvious sign of toxicity. We did not succeed in reproducing in rats the Bi toxicity observed in patients some years ago.

Animals↗

Aluminium determination in the skin of patients with and without end-stage renal failure.

Aluminium (Al) concentration in the skin was determined by inductively coupled plasma optical emission spectrometry to look for a correlation between Al exposure and skin content in patients with end-stage renal failure. Skin Al concentrations were higher in dialyzed patients than in the nondialyzed group (1.02 +/- 0.30 vs. 0.26 +/- 0.10 micrograms/g; p less than 0.001). Moreover, in the dialyzed group, the patients treated for more than 100 months had a higher concentration of Al in the skin than the others (1.20 +/- 0.26 vs. 0.80 +/- 0.18 micrograms/g; p less than 0.05). Al skin content correlated better with the deferoxamine infusion test (DIT) than with Al blood plasma concentration. In conclusion, our data confirm that the DIT is a valuable tool for the evaluation of body Al content.

Adult↗

Plasma and urine aluminium concentrations in healthy subjects after administration of sucralfate.

1. Sucralfate (basic sucrose aluminium sulphate), a topical intestinal agent, was administered in suspension or granule form to 25 healthy subjects at a total dose of 4 g day-1 for 21 days. Aluminium in plasma and 24 h urine samples was assayed before, during and after administration of sucralfate by inductively coupled plasma optical emission spectrometry. 2. Sucralfate produced significant increases in plasma and urine aluminium concentrations. On average, plasma aluminium increased from about 2 micrograms 1-1 to more than 5 micrograms 1-1 and 24 h urine aluminium increased from less than 5 micrograms to more than 30 micrograms. Both plasma and urine aluminium concentrations decreased rapidly after sucralfate was stopped. However, urinary aluminium concentrations remained higher than normal 5 and 10 days after discontinuation of sucralfate administration. Moreover subjects receiving sucralfate granules had significantly higher average urinary excretion of aluminium than subjects receiving the suspension. 3. The small but significant increase in plasma and urine aluminium following sucralfate administration in therapeutic doses may reflect intestinal absorption of aluminium. Although such absorption would appear to be moderate in healthy subjects, it is suggested that aluminium-based treatments should be used only intermittently, especially in patients with renal disorders.

Adult↗

Effects of etretinate on the distribution of elements in rats.

We studied in the rat the effects of the drug etretinate (Tigason), given at three doses 3, 10, and 30 mg/kg body wt for 1 mo, on the concentrations of Na, K, Ca, Mg, Fe, S, P, Cu, and Zn in the plasma, brain, thymus, heart, liver, lung, kidney, testicle, muscle, and bone. The elements were simultaneously determined in tissues after nitric acid dissolution by inductively coupled plasma emission spectrometry using a JY 48 instrument. At the dose of 3 mg/kg, etretinate did not induce any statistically significant modifications of the element distribution. At the dose of 10 mg/kg, the main observed modifications were in plasma an increase of copper (+38%) and a decrease of zinc (-25%). At the highest dose of 30 mg/kg, some variations of the concentrations of elements in tissues were observed. But, on no account did retinoids induce an alteration of the mineral composition of bone, despite obvious macroscopic bone alterations.

Animals↗

The distribution of elements in the tissues of Watanabe Heritable Hyperlipidemic Rabbits.

A deficiency or an excess of some elements in the diet is reported to modify the concentration of cholesterol in plasma, and, conversely, a reduction of cholesterol in the diet decreases zinc in plasma. We have studied the distribution of elements Na, K, Ca, Mg, Fe, Cu, Zn, S, P, and Mn in the tissues, plasma, heart, aorta, lung, liver, spleen, kidney, thymus, and brain of New Zealand White rabbits (NZW) and of Watanabe Heritable Hyperlipidemic rabbits (WHHL). The WHHL rabbits had a massive hypercholesterolemia (7.45 +/- 1.2 g/L) induced by a lack of liver low density lipoprotein receptors. The concentrations of elements in the tissues of the control NZW rabbits were very similar to those found in the normal rat. In WHHL, compared to NZW, besides the very important increase of total phosphorus in plasma explained by the augmentation of phospholipids, there was an increase of plasma copper (+44%) and zinc (+36%). The other noticeable changes were an increase of iron in heart (+19%), sulfur, and zinc in liver (+15% and +18%). The other changes observed in WHHL rabbits were, besides the increase of ceruloplasmin, the increase of vit E (+468%) and MDA (+62%). In conclusion, despite a massive increase of lipids in plasma, there was no major disturbance of element distribution in WHHL rabbits.

Animals↗

Effects of thyroparathyroidectomy on the distribution of bromine and iodine in rat tissues.

The concentrations of iodine (I) and bromine (Br) were measured by inductively coupled plasma mass spectrometry in the plasma, kidney, heart, liver, and brain of control and thyroparathyroidectomized (TPTX) rats without and with an additional intake of either NaI or NaBr, 0.5 and 5 mumol/kg/d, respectively, for 21 d. In all groups, the highest concentrations of I and Br were found in the plasma. TPTX did not modify the concentrations of I in tissues, but slightly increased Br in plasma (+33%) and kidney (+24%). The additional intake of I with the drink induced an increase of I concentrations in the tissues tested (from 54 to 191%), except brain, both in control and TPTX rats. This additional intake of I also increased Br levels in the plasma of control (+24%) and TPTX rats (+53%). The additional intake of Br with the drink induced an increase of Br levels in all the tested tissues, brain included (from 85 to 284%). The augmentation was higher in the tissues, particularly brain, of TPTX rats than of controls. The increase of Br in brain after an additional intake contrasts with the absence of increase of I given in the same conditions. This difference between I and Br probably results from the smaller radius of Br ion in comparison with I ion radius. In conclusion, TPTX did not modify the distribution of I in the tested tissues, but slightly increased the concentrations of Br in plasma and kidney.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗