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Biomedical subjects

P Courpron

Publications and source records attributed to P Courpron.

At least 19 recordsLinked to original sources

Functions and tocopherol content of blood platelets from elderly people after low intake of purified eicosapentaenoic acid.

Elderly people present an increased incidence of atherosclerosis and vascular cerebral damages, associated with blood platelet hyperactivity and a stimulation of arachidonic acid metabolism in vivo. The effects of a low intake of purified eicosapentaenoic acid (EPA) on platelet hyperactivity in old human subjects has been investigated. In a randomized, double blind study, 8 people took during 2 months a daily intake of 100 mg of eicosapentaenoic acid (EPA) given as a triglyceride (1,3-dioctanoyl,2-eicosapentaenoyl-glycerol), and 8 other subjects ingested a placebo. A slight, but significant reduction of platelet-rich plasma aggregation in response to epinephrine and arachidonic acid occurred after EPA intake, as well as a decreased aggregation of washed platelets induced by thrombin, although collagen- and U-46619-induced aggregations were not significantly modified. EPA intake failed to affect arachidonic acid metabolism in thrombin-stimulated platelets or in clotted venous blood. The urinary excretion of thromboxane, 6-keto-PGF1 alpha and their 2,3-dinor-metabolites was also not modified. Similarly, no change in the plasma and platelet lipid fatty acid compositions could be observed. Platelet, but not plasma, alpha- and gamma-tocopherol were enhanced by EPA intake. An increase of platelet vitamin E has been associated with a decrease of aggregation, especially in vitamin E-deficient subjects, like elderly people. Therefore, low intake of EPA might have contributed to inhibit platelet aggregation by increasing cellular vitamin E.

Administration, Oral

Platelets and aging. I--Aggregation, arachidonate metabolism and antioxidant status.

Platelet functions were investigated in sixteen old (78-94 years) and eight young (25-35 years) subjects. Whole blood platelet aggregation induced by collagen was higher in the elderly. Similarly, aggregation of platelet rich plasma and plasma-free platelets induced by various agents was increased but the collagen-induced release of ATP was reduced. In agreement with the enhanced platelet aggregability, the increase of thromboxane formation (under thrombin stimulation) was also noted in platelets from elderly people. To further assess platelet and vascular function in vivo, we measured the excretion of urinary TXB2, 2,3-dinor TXB2, 6-keto-PGF1 alpha and 2,3-dinor-6-keto-PGF1 alpha. The four metabolites were all increased in the elder population. In addition, a significant reduction of platelet vitamin E was observed in the elderly people, although the plasma content was normal. These results indicate numerous modifications of platelet behaviour with aging. They include the increased platelet susceptibility to aggregation, and the depletion of ATP granule content, which could reflect an activation in vivo in agreement with the enhanced urinary excretion of thromboxane and prostacyclin metabolites. We hypothesize that platelet hyperactivity associated with the enhanced oxygenated metabolism of arachidonic acid could be linked to vitamin E depletion. These changes may reveal a prethrombotic state in the elderly population.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid

Age-related changes in cancellous bone structure. A two-dimensional study in the transiliac and iliac crest biopsy sites.

In 94 pairs of large sections of normal iliac bone (53 men, 41 women, aged 20-80 years) we confirmed trabecular bone area (B.Ar) and the mean number of trabeculae per mm (Tb.N) to decline with age, in areas representative of the transiliac (TI) and iliac crest (IC) biopsy in both sexes, whereas mean trabecular width (Tb.Wi) did not decrease. Our data also confirm that disappearance of entire elements is the main event in age-related loss of trabecular bone. In addition, our study demonstrated that Tb.Wi is lower in women than in men in the IC site, and a preferential loss of the thinner trabeculae could be seen in this group. Up to 50 years, Tb.N was found higher in women in both sites. B.Ar and Tb.Wi values are markedly higher in the TI site (+/- 15%); Tb.N values were similar. Measured and calculated Tb.Wi values show systematic differences. In a pilot study in 14 IC biopsies with widely diverging B.Ar values, we tested the validity of several equations currently used for derived parameters in the structural analysis of cancellous bone sections. The equation for mean trabecular number passed the test, whereas the validity of the equations for mean trabecular separation and Tb.Wi appeared limited. We found anisotropy of iliac bone to increase as B.Ar decreases.

Adult

Effects of linoleic acid and gamma-linolenic acid intake on platelet functions in elderly people.

Sixteen old subjects were given daily dietary supplement of lg of linoleic acid and lg of gamma-linolenic acid (primerose oil) or 2g of linoleic acid (sunflower oil) for periods of two months. Haemostatic parameters, platelet aggregation, exogenous and endogenous arachidonic acid metabolism were investigated before and after the intake. Diets did not induce any significant change in haemostatic parameters (bleeding time, levels of anti-thrombin III, plasminogen and plasma beta-TG and PF4). Platelet rich plasma aggregation induced by collagen and arachidonic acid were significantly reduced after linoleic acid (18:2n-6) intake. In contrast, gamma-linolenic acid (18:3n-6) supplement did not alter aggregation. However, thromboxane B2 formation (under stimulation) and vitamin E level in platelets (but not in plasma) were decreased after 18:3n-6 as compared to 18:2n-6 intake. The mechanism of thromboxane B2 decrease is unclear. Nevertheless, we may speculate that beneficial effect of this decrease could be counterbalanced by the decreased platelet vitamin E. We conclude that intake of 18:2n-6 or 18:3n-6 does not affect much platelet functions in elderly people.

8,11,14-Eicosatrienoic Acid

[Physiological osteopenia: histomorphometric findings].

The construction of bone results from the collaborative work of functional constituents; destructive cells or osteoclasts, the activity of which induces that of other, constructive cells, the osteoblasts. During the whole period of growth, construction surpasses destruction. During the rest of life the destructive process predominates, whence a physiological osteopenia, which affects man as well as woman, but which accelerates in the latter during the postmenopausal years. The measurement of this physiological osteopenia by bone biopsy shows clearly that it is due to a simultaneous diminution of these two processes. Common osteoporosis, of early appearance, presents in 50% of cases as the chemical and biological expression of an acceleration of normal processes. 30% of them, on the contrary, are accompanied by an excess of destruction, whereas the rate of construction remains normal. In about 20% of cases it is the constructive phase which is depressed, destruction remains normal.

Adult

Anabolic effect of human parathyroid hormone fragment on trabecular bone in involutional osteoporosis: a multicentre trial.

After baseline studies, 21 patients with osteoporosis were treated with human parathyroid hormone fragment (PTH 1-34) given as once-daily subcutaneous injections for 6-24 months. The dose used did not cause hypercalcaemia even in the first few hours after injection. Calcium and phosphate balances improved in some patients, but there was no significant improvement in the group values. There were, however, substantial increases in iliac trabecular bone volume: the mean increase, confirmed by repeat blind measurements, was 70% above mean baseline volume. The new bone was histologically normal. Those patients who had the largest increases in 47Ca-kinetic and histomorphometric indices of new bone formation showed the greatest increases in trabecular bone volume, suggesting that treatment with human parathyroid hormone fragment caused a dissociation between formation and resorption rates that was confined to trabecular bone. Since vertebrae are four-fifths composed of trabecular bone, this hormone fragment may prove useful in treating patients with the crush fracture syndrome.

Aged

Niflumic acid-induced skeletal fluorosis: iatrogenic disease or therapeutic perspective for osteoporosis?

A case of skeletal fluorosis induced by prolonged treatment with niflumic acid, a fast-acting non-steroid antiinflammatory agent, is reported in a 35-year-old woman suffering from rheumatoid arthritis and treated, in addition, with corticosteroids. The case report discussed is, to our knowledge, the third of its kind regarding bone fluorosis resulting from use of this nicotinic derivative. This clinically asymptomatic case of skeletal fluorosis was discovered, as in the 2 previously reported cases, by the examination of bone X-ray (performed as part of the routine work-up for rheumatoid arthritis) which showed evident osteosclerosis. Quantitative histologic study of iliac crest biopsy revealed marked increase in trabecular bone volume and osteoid volume, suggestive of fluorosis. Abnormally high urine and bone fluoride confirmed the diagnosis. After ruling out a hydrotelluric source of fluorine, the patient's fluorosis was linked to chronic use of niflumic acid, following the publication in 1978 of the 2 previously reported cases affected by this drug. The fluorine contained in niflumic acid induced a marked densification of trabecular bone in all 3 cases. Long-term clinical and pharmacokinetic studies will be required to determine whether or not niflumic acid can be employed in the prevention or treatment of both of apparently idiopathic osteoporosis or corticosteroid-induced osteoporosis.

Adult

Mean wall thickness of trabecular bone packets in the human iliac crest: changes with age.

The mean wall thickness (MWT) of packets of trabecular bone was measured in undecalcified iliac crest bone samples of 36 normal subjects (14 female and 22 male) under polarized light. The mean wall thickness was 49.7 +/- 8.7 microns at a mean age of 50.9 years. There existed a significant decrease of MWT with advancing age. With an appositional rate of 0.72 micron/day, the mean formation time of iliac trabecular bone packets is 69 days. The decrease of MWT with age corresponds to a decrease in bone formation at the basic multicellular unit (BMU) level with aging and can partly explain the physiological senile osteopenia.

Adolescent

Serum alpha-fetroprotein concentration in adult patients under corticoid, estroprogestative or androgen therapy.

The serum alpha-fetoprotein concentration was measured by radioimmunoassy in 41 women with or without hormonal contraception, 21 patients with rheumatoid arthritis given corticosteroids or not, and 6 patients under androgen therapy for aplastic anemia. None of these therapies induced any significant variation of the serum alpha-fetoprotein level. More extensive studies are needed to investigate the possible effect of these hormones on the metabolism of this protein at a cellular level.

Adult

[Clinical, biological and histological effects of ethane-1-hydroxy 1, 1-diphosphonate (EDHP) in Paget's disease].

The diphosphonates are analogues of the pyrophosphates that are capable of resisting enzymatic destruction and they become fixed in the bone tissue where they have a powerful inhibitory action on osteoclastic resorption and on osteoid mineralization. Ethane-1-hydroxy-1, 1-diphosphonate (EDHP) was administered by mouth at the dose of 20 mg/kg/day over a period of 3 to 6 months to 11 patients with painful Paget's disease. A marked analgesic effect was noted in 7 of the 11 patients. Spectacular metabolic effects were noted with return to normal of the total hydroxyprolinuria/24 h and of the alkaline phosphatases 3 months after treatment in 6 of the 11 treated subjects and a marked improvement in these parameters in 4 other patients. Histologically, there was almost total disappearance of osteoclasia and of osteoblastosis in the affected areas. Clinically, the secondary effects presented in some cases as diarrhoea, and an early and marked rise in phosphoraemia was recorded. Histologically, hyperosteoidosis was seen, equally in the affected and nonaffected zones. This resulted from an almost complete stoppage in the calcification of the osteoid as indicated by the double labelling by tetracycline. The review of the literature shows that considerable therapeutic effects are obtained even with very small doses of EHDP, e.g., 10 mg/kg/day for 3 months, but that these are often accompanied by more marked secondary effects. The diphosphonates appear to be a promising treatment for Paget's disease.

Alkaline Phosphatase