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Biomedical subjects

Y Touitou

Publications and source records attributed to Y Touitou.

At least 127 records · Page 7Linked to original sources

Comparison of the feedback effect of magnesium and calcium on parathyroid hormone secretion in man.

Administration of high doses of magnesium is known to produce a decrease in parathyroid hormone (PTH) secretion in human patients but the effect of magnesium on the secretion of PTH in healthy man is not known. We have looked at the effect of a relatively moderate i.v. dose of magnesium (7.08 mmol) in seven healthy men. In addition and for comparison the effect of calcium (4.25 mmol) was studied. Two magnesium salts were considered, magnesium sulphate (MgSO4) and magnesium pyrrolidone carboxylate (MgPC). Four i.v. injections were given at 08.00 h (MgPC, NaCl (control), MgSO4 and Ca gluconate), with an interval of 1 week between each injection. Whatever the magnesium salt the variations in plasma concentrations of magnesium were the same whereas no change in erythrocyte magnesium was observed. Plasma concentration of C-terminal PTH did not show significant variations after MgPC or saline injection. Both MgSO4 and Ca gluconate produced a statistically significant 30% decrease in plasma PTH levels 45 min after the injection. The effect was more sustained with calcium (2 h) than with magnesium (45 min). The urinary excretion of magnesium was significantly higher after injection of MgSO4 than after MgPC. These results suggest that magnesium was, on a molar basis, less potent than calcium in regulating PTH secretion in vivo, that the nature of the magnesium salt used must be kept in mind for the interpretation of the effect of magnesium on PTH secretion in vivo and that the decrease in plasma PTH can partly explain the larger urinary excretion of magnesium after MgSO4 than after MgPC.

Adult↗

Circadian rhythm in the membrane of circulating human blood cells: microviscosity and number of benzodiazepine binding sites. A search for regulation by plasma ions, nucleosides, proteins or hormones.

Circadian rhythms in both the number of peripheral type binding sites for benzodiazepines in platelet membranes and the microviscosity of the erythrocyte membrane were demonstrated in 7 healthy men. Neither variable appeared to be linked to each other, or regulated by the plasma concentrations of total or free cortisol, testosterone, potassium, magnesium, calcium, cAMP, cGMP or proteins or by the erythrocytic concentration of magnesium or potassium or by the plasma cAMP:cGMP ratio or by the ratio of intra-erythrocyte:plasma concentrations of potassium or magnesium. A highly significant negative correlation was found between the microviscosity of the erythrocyte membrane and the activity of the membrane-bound enzyme, methyltransferase I. Such a correlation was validated both on raw data and on 24 hr-means (r = 0.84; P less than 0.01). A circadian rhythm in the activity of this enzyme was also demonstrated. Moreover, a highly significant correlation was also found between plasma transcortin concentration (TRC) and microviscosity (r = 0.50, P less than 0.01), and between TRC and methyltransferase I activity (r = 0.61, P less than 0.01). Such findings may constitute clues towards the understanding of the regulation of the circadian rhythm in the fluidity of the red blood cell membrane in man and guide future steps with regard to the role of this rhythm upon the availability of drug binding sites at the cell surface.

Adult↗

[The aging of biological rhythms in man].

The characteristics of the rhythms of some biological variables (peak location in the time scale, mean level, amplitude...) may be modified in elderly subjects when compared with young ones in the three spectral fields (ultradian, circadian and infradian). The purpose of this review is to round up the question of such possible modifications with age of endocrine functions (adrenals, gonads, pituitary, parathyroid, pineal, vitamin D...) and of others (body temperature, plasma proteins, cations...). These modifications, if any, may be interpreted as a change in the adaptability of aged subjects to environmental factors. The loss or decrease of adaptation capacity with aging is of course worth quantifying. The concept of biological rhythms has thus to be taken into account in any study dealing with aging.

Aged↗

Aspects of chronopharmacology and chronotherapy in pediatrics.

Pediatric chronopharmacological findings until now have been limited to circadian changes in children from ages 6 to 15 years. This means that data in newborns and even in infants of 1 year are not available and other bioperiodicities with periods of about-1-year (infradian rhythms) have not been explored in older children. Biologic time-related changes have been documented for phenytoin and theophylline with regard to pharmacokinetics, for orciprenaline with regard to bronchodilation, and for corticosteroids as well as anticancer agents with regard to their effectiveness. Despite the limited number of experiments performed to date, it is already possible to state that a chronopharmacological approach provides better precision in pharmacologic study than the conventional approach not using time-related data and better therapeutics can be achieved with the help of chronopharmacological facts since appropriate timing in administration of medicine usually enhances its desired and/or reduces its undesired effects.

Adrenal Cortex Hormones↗

Prevalence of magnesium and potassium deficiencies in the elderly.

Concentrations of magnesium and potassium in erythrocytes and plasma were determined in a population of 381 unselected elderly men and women, most of them in their eighties. The effects of biological factors (age, sex, weight) and a large set of pathological conditions, malignant or not, were examined. Analyses of variance showed a relation between age and concentrations of plasma potassium and between weight and concentrations of plasma magnesium. The chi-square test showed correlations between low concentrations of plasma magnesium and diabetes, abuse of alcohol and tobacco, and also between low values for erythrocyte magnesium and hypertension. Low values for plasma potassium were correlated with hypertension whereas high values were correlated with cardiovascular disease. Although some of the differences in the mean concentrations observed were statistically significant, these differences were always small. Most interesting was the distribution of the concentrations of the cations. This study shows that assays of both of these cations in erythrocytes were better than assays in plasma to evidence a deficiency. Indeed, about 20% of the studied population had low concentrations of both erythrocyte potassium and magnesium, whereas 2 and 10% had low values for plasma potassium and magnesium, respectively. This study underlines the large prevalence of magnesium and potassium deficiencies in the elderly, an observation we could not attribute to pathology or treatment. Routine electrolyte studies therefore appear to be justified in aged human subjects.

Age Factors↗

Decreased nocturnal plasma melatonin peak in patients with a functional alteration of the retina in relation with uveitis.

A functional alteration of the retina is present in patients suffering from uveitis. Because of the relation between the pineal gland and the retina we documented possible modifications of melatonin secretion in patients with uveitis. Plasma melatonin was assayed in 19 patients and 16 age-matched controls. Blood samples were drawn at the known high and low points of the circadian rhythm of the hormone, i.e. 02.00 and 11.00 h, respectively. We found that the nocturnal peak of plasma melatonin was greatly decreased (45%) in patients with uveitis. These data cannot be related to the impairment of retinal melatonin synthesis alone. The possibility exists that the decline of the nocturnal peak of melatonin we have reported is due to a pineal inflammation in patients with uveitis, as observed in the experimental autoimmune uveitis induced in rats by retinal S-antigen.

Adolescent↗

Lack of circadian rhythm in plasma levels of 3,4-dihydroxyphenylethyleneglycol in healthy human subjects.

In order to investigate the possible existence of a circadian rhythm in plasma free and sulfate-conjugated 3,4-dihydroxyphenylethyleneglycol (DOPEG), the plasma levels of this metabolite (and for comparison, of melatonin and cortisol) were measured in seven healthy volunteers at 4-h intervals over a period of 24 h. Plasma concentrations of melatonin and cortisol showed distinct diurnal variations with acrophases at 2.5 h and 8.5 h, respectively. In contrast, plasma free DOPEG levels were relatively stable over the 24-h period studied. Sulfate-conjugated and free + sulfate-conjugated DOPEG levels showed a slight, non-significant increase in the early afternoon. These results indicate that in contrast to plasma 3-methoxy 4-hydroxyphenylethyleneglycol, plasma free and conjugated DOPEG levels do not exhibit a circadian rhythm.

Adult↗

Age-related changes in both circadian and seasonal rhythms of rectal temperature with special reference to senile dementia of Alzheimer type.

The biological rhythms of rectal temperature were documented in young (circadian variations) and elderly (circadian and seasonal variations) human subjects either in apparent good health or suffering from senile dementia of Alzheimer type (SDAT). All the subjects were synchronized. Data obtained showed a decrease of the body core temperature rhythm amplitude in the healthy elderly for each documented season but not in patients with SDAT. Seasonal variations in these rhythms were observed in these elderly groups of persons.

Aged↗

[Circadian and seasonal changes of the inducer:suppressor ratio (OKT4+:OKT8+) in venous blood of healthy adults].

Circadian and seasonal variations in the T helper: T suppressor-cytotoxic ratio were investigated in peripheral blood from five healthy young men. Mononuclear cells were isolated on Ficoll-Paque gradient, then incubated with OKT4 and OKT8 monoclonal antibodies. Plasma cortisol was determined in four of these seven time series. Large interindividual differences were documented and statistically validated for the 24-hr.-means of total lymphocytes, OKT4+:OKT8+ ratio, and of plasma cortisol (both total and free). For a pooled data, a circadian rhythm was demonstrated by cosinor (p less than 0.001) for total lymphocytes (acrophase at 1.00 hr.), total plasma cortisol (acrophase at 10.30 hrs.) and free plasma cortisol (acrophase at 9.50 hrs.), but not for OKT4+:OKT8+ ratio. This index however exhibited a statistically significant circadian rhythm in April and August, but not in November. Its double-amplitude exceeded 80% of the 24-hour-mean and its acrophase was localized at 6.40 hrs. in April and at 22.30 hrs. in August. Its 24-hr-mean was higher in August as compared to April and November. The circadian rhythm in the OKT4+:OKT8+ ratio did not seem to be related to that of plasma cortisol. Both circadian and seasonal variations need to be taken into account when investigating the regulations of immune variables such as T helper: T suppressor-cytotoxic ratio.

Adult↗

[Feedback of the magnesium ion on the parathyroid hormone: differences in the action of magnesium sulfate and pyrrolidone carboxylate].

Fourty-five minutes after an intravenous injection of Mg SO4 (170 mg of element Mg), in 7 young and healthy men, a significant decrease in circulating 53-84 PTH has been observed. An injection of magnesium pyrrolidone carboxylate (170 mg of Mg) failed to induce changes in plasma levels of PTH. The urinary excretion of Mg was 2-fold higher after the injection of Mg SO4 than after the injection of magnesium pyrrolidone carboxylate. For both magnesium salts used, the time patterns of plasma magnesium concentrations were the same and red blood cells magnesium was not increased. These results suggest that, in our experimental conditions, the retention of magnesium was higher after magnesium pyrrolidone carboxylate than after Mg SO4 and that the drop in plasma PTH could partly explain the larger urinary excretion of magnesium after Mg SO4.

Adult↗

Differences between young and elderly subjects in seasonal and circadian variations of total plasma proteins and blood volume as reflected by hemoglobin, hematocrit, and erythrocyte counts.

Circadian and seasonal rhythms in total plasma proteins were documented in healthy young men (around 24 years old), and in elderly subjects (both sexes), including senile-dementia patients in their eighties. The concentration of plasma proteins within a given group changed predictably (7-13%), depending on the hour of sampling and the season. Concentrations decreased noticeably around 04:00 h, then peaked around 08:00 h (shortly after waking). The 24-h mean concentrations of total plasma proteins were lower in the elderly groups than in the young men. But the seasonal variations of the 24-h mean values were strikingly larger in the elderly groups (7-8 g/L) than in the young men (2-5 g/L). Moreover, the circadian profiles of plasma proteins differed from the profiles of hematocrit, hemoglobin, and erythrocyte counts. Evidently, circadian variations of blood volume may not be the only element accounting for the variations of plasma protein concentrations. We suggest that the rhythms in plasma protein concentrations be taken into account when reference values are set. Circadian and seasonal variations in plasma proteins may also significantly affect the transport and binding of drugs, especially in the aged.

Adult↗

Plasma ferritin in old age. Influence of biological and pathological factors in a large elderly population.

The effects of biological (age, sex, weight) and pathological factors on plasma ferritin concentrations were documented in 776 unselected elderly patients aged 80.9 +/- 9.7 yr. A marked shift towards high values (159 +/- 142 micrograms/l) was observed in this elderly population together with the persistence of the well-known sex-related difference in ferritin levels (higher levels in men). Twenty-five percent of the population had high levels of ferritin (greater than or equal to 220 micrograms/l) but 75% of these high values (i.e. 18.5% of the population) could be readily explained by their known association with a particular pathology (inflammatory syndrome, renal failure, cardiovascular diseases, alcoholism). Only 6% of the population had unexplained high ferritin concentrations. Therefore, our data strongly suggest that the repeatedly reported increase of ferritin in the aged population is merely related to an age-associated pathology and may not be a normal physiological event occurring during the process of aging.

Aged↗

Biological and pathological factors affecting plasma gamma-glutamyl transpeptidase and alkaline phosphatase activity in the elderly.

A high percentage of abnormally elevated plasma alkaline phosphatase (AP) and gamma-glutamyltranspeptidase (GGT) was found in a homogeneous population of 741 elderly subjects. The respective role of pathological and biological factors (age, sex, weight) upon the two plasma enzymatic activities has been analyzed. In disagreement with previous reports, it was observed that abnormal AP and GGT values could be readily explained by their association with specific diseases. The apparent relationship between abnormal levels of plasma AP and GGT activities and age, sex or weight reflected merely a different distribution of the pathology according to these biological parameters. In the absence of non-specific elevations of plasma AP and GGT activities with age, the usual reference values for these tests, although established on younger populations, still apply to the aged.

Age Factors↗

o,p'-DDD (mitotane) treatment for Cushing's syndrome: adrenal drug concentration and inhibition in vitro of steroid synthesis.

o,p'-DDD is an inhibitor of adrenal steroid synthesis currently used for therapy of Cushing's syndrome. Conflicting data have been published on the relationship between the plasma level of the drug and its clinical and biological effects. The levels of o,p'-DDD and o,p'-DDE in various tissues obtained from treated patients have been measured and are compared with data on in vitro steroidogenesis in adrenal tissues from the same patients. o,p'-DDD was found in all samples and o,p'-DDE in half of them, both levels being high when the tissue lipid concentration was high. There was considerable variability in lipid content from one tissue to another and within a tissue from one sample to another; only the drug to lipid ratio seems able to provide a reproducible index of drug entry into a tissue. No relationship was found between the tissue concentration of the drug and the total dose administered or inhibition of the steroid biosynthetic step studied.

17-alpha-Hydroxyprogesterone↗

Magnesium: metabolism and hormonal regulation in different species.

1. The magnesium ion is of great importance in physiology by its intervention in 300 enzymatic systems, its membrane role and its function in neuromuscular excitability. 2. The skeleton is the first pool of magnesium in the animal body. 3. For intestinal absorption, renal metabolism, bone accretion and resorption, magnesium shows analogies with calcium. 4. Magnesium exchange between extracellular, cellular and skeletal compartments are very precisely controlled. 5. Parathyroid hormone, 1 alpha, 25-dihydroxy-vitamin D3, calcitonin and estrogens are the principal hormone systems implicated in magnesium metabolism. 6. The kidney is the principal site of magnesium excretion and shows important magnesium regulation mechanisms.

Animals↗

Age- and sex-associated modification of plasma melatonin concentrations in man. Relationship to pathology, malignant or not, and autopsy findings.

Plasma melatonin concentrations were determined in 757 unselected elderly patients aged 80.9 +/- 9.7 years. The daytime (8-9.30 h) plasma levels of melatonin were in the so-called normal range in only one third of the population whereas 65% of the subjects had abnormal levels of the hormone, most often decreased i.e. less than 0.17 nmol/l (53%) and sometimes increased i.e. 0.43 nmol/l or higher (12%). A control group of healthy elderly subjects showed the same distribution as the entire population. A sex-difference with significantly higher levels of plasma melatonin in elderly women was observed. With respect to pathology and autopsy findings high levels of the hormone correlated with cancer, chronic renal failure, cardiovascular disease, biological inflammatory syndrome and diabetes. Low levels correlated with neurologic disease, tobacco or alcohol addiction. However, some of these relations were found to be sex-related as they were observed in women but not in men. Our data indicate that pineal function seems to be often altered in elderly human subjects and suggest potential diagnostic applications of melatonin determination.

Age Factors↗