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Biomedical subjects

J Vanderpas

Publications and source records attributed to J Vanderpas.

17 recordsLinked to original sources

Selenium decreases thyroglobulin concentrations but does not affect the increased thyroxine-to-triiodothyronine ratio in children with congenital hypothyroidism.

Compared with euthyroid controls, patients with congenital hypothyroidism (CH) who are receiving L-T(4) treatment show elevated serum TSH relative to serum T(4) concentrations and increased T(4)/T(3) ratio. These abnormalities could be the consequence of impaired activity of the selenoenzymes deiodinases on which patients with CH rely to convert the ingested L-T(4) into active T(3). Eighteen patients (0.5-15.4 yr), diagnosed with CH in infancy, received selenomethionine (SeM, 20-60 microg selenium/day) for 3 months. The study took place in Belgium, a country where selenium intake is borderline. Compared with the values observed in age- and sex-matched euthyroid controls, patients with CH had decreased selenium, thyroglobulin and T(3) concentrations and increased TSH, reverse T(3), and T(4) concentrations and T(4)/T(3) ratio at baseline. Selenium supplementation caused a 74% increase in plasma selenium values but did not affect the activity of the selenoenzyme glutathione peroxidase used as a marker of selenium status. SeM abolished the TSH difference observed between CH patients and euthyroid controls at baseline and caused a significant decrease in thyroglobulin values. Thyroid hormone concentrations were not affected by SeM. In conclusion, our data suggest that selenium is not a limiting factor for peripheral T(4)-to-T(3) conversion in CH patients. In contrast, we find indirect evidence that SeM improves thyroid hormones feedback at the hypothalamo-pituitary level and decreases stimulation of the residual thyroid tissue, possibly suggesting greater intracellular T(4)-to-T(3) conversion.

Adolescent↗

[Kashin-Beck disease in China: osteochondrodysplasia related to nutrition and environment].

Kashin-Beck disease is a endemic juvenile osteochondrodysplasy, whose association with selenium deficiency and/or mycotoxin toxicity has been corroborated by epidemiological studies in China, including Tibet. Iodine deficiency appears to be a new etiological factor. Together with the geographical and epidemiological exploration of the disease, scientific multidisciplinary investigations (clinics, radiological imaging, histology, environmental and molecular biology) should afford to understand the cause of the disease before it disappears as a consequence of the evolution of the Chinese Society, including in Tibet.

Adult↗

Kashin-Beck osteoarthropathy in rural Tibet in relation to selenium and iodine status.

BACKGROUND AND METHODS: Kashin-Beck disease is a degenerative osteoarticular disorder that is endemic to certain areas of Tibet, where selenium deficiency is also endemic. Because selenium is involved in thyroid hormone metabolism, we studied the relation among the serum selenium concentration, thyroid function, and Kashin-Beck disease in 575 subjects 5 to 15 years of age in 12 villages around Lhasa, Tibet, including 1 control village in which no subject had Kashin-Beck disease. Clinical, radiologic, and biochemical data were collected. RESULTS: Among the 575 subjects, 280 (49 percent) had Kashin-Beck disease, 267 (46 percent) had goiter, and 7 (1 percent) had cretinism. Of the 557 subjects in whom urinary iodine was measured, 66 percent had a urinary iodine concentration of less than 2 microg per deciliter (157 nmol per liter; normal, 5 to 25 microg per deciliter [394 to 1968 nmol per liter]). The mean urinary iodine concentration was lower in subjects with Kashin-Beck disease than in control subjects (1.2 vs. 1.8 microg per deciliter [94 vs. 142 nmol per liter], P<0.001) and hypothyroidism was more frequent (23 percent vs. 4 percent, P=0.01). Severe selenium deficiency was documented in all villages; 38 percent of subjects had serum concentrations of less than 5 ng per milliliter (64 nmol per liter; normal, 60 to 105 ng per milliliter [762 to 1334 nmol per liter]). When age and sex were controlled for in a multivariate analysis, low urinary iodine, high serum thyrotropin, and low serum thyroxine-binding globulin values were associated with an increased risk of Kashin-Beck disease, but a low serum selenium concentration was not. CONCLUSIONS: In areas where severe selenium deficiency is endemic, iodine deficiency is a risk factor for Kashin-Beck disease.

Adolescent↗

[The general practitioner and electrolyte disturbances].

Serum electrolytes (sodium, potassium) are frequently included in usual clinical chemistry orders, for example in annual checkups in target groups. The clinical significance of abnormalities of these parameters, and the logical order of complementary analyses is reviewed.

Family Practice↗

[The general practitioner and abnormal thyroid function screening].

The high frequency of thyroid diseases justifies the measurement of serum TSH in regular checkups. If found normal in non-goitrous patients, this measurement is self-sufficient, but pregnant women should also be screened for antithyroid antibodies because they have an increased risk of post-partum Hashimoto's disease. Abnormal TSH concentrations suggesting hyperthyroidism (TSH < 0,3 mU/l) or hypothyroidism (TSH > 5 mU/l) need free T4 and free T3 complementary determinations, and positive anti-thyroid antibodies may indicate Graves-Basedow's disease in case of hyperthyroidism or Hashimoto's disease in case of hypothyroidism. More recently, measurement of anti-TSH-receptor antibodies had allowed the diagnosis and a follow-up tool in some cases of thyroid diseases.

Adolescent↗

Selenium status in pregnant women of a rural population (Zaire) in relationship to iodine deficiency.

Endemic myxoedematous cretinism has been associated with combined selenium and iodine deficiency in several areas of Zaire. To determine selenium and iodine status across the country, serum selenium and thyroid function parameters including urinary iodide were determined at prenatal clinics in 30 health centres of rural villages distributed over the whole country. Only in Bas-Zaire was the mean serum selenium level similar to that in non-deficient areas (80-120 ng/ml); in the regions of Bandunda and Kasai levels were marginally decreased (55-80 ng/ml), and in Kivu, Haut-Zaire, Equateur and Shaba they were marginally or moderately decreased (< 55 ng/ml). The frequency of abnormally low urinary iodide (< 5 micrograms/dl) varied from 20% in the region of Bas-Zaire to 50% in Kasai (P < 0.001), and to still higher percentages in the 5 other regions of Zaire (Bandundu, 57%; Kivu, 63%; Equateur, 72%; Shaba, 76%; Haut-Zaire, 84%). With the exception of Bas-Zaire, biochemical maternal hypothyroidism (serum TSH > 5mU/l) was present in every region, with a frequency ranging from 3% in Kivu to 12% in Equateur. Iodine deficiency affects most of the Zairean population and requires public health measures on a larger scale than previously estimated. Combined iodine and selenium deficiency affects Equateur, Haut-Zaire and Kivu, where endemic myxoedematous cretinism occurs, but also Shaba, where it was not previously described. Besides combined iodine and selenium deficiency which is permissive, another factor (thiocyanate?) must be taken into account to explain the peculiarly elevated prevalence of endemic myxoedematous cretinism in Central Africa.

Congenital Hypothyroidism↗

[Congenital deficiencies in bile acid synthesis: from diagnosis to treatment].

Bile acids represent the principal excretion pathway of cholesterol. Their synthesis involves hydroxylations of the sterol nucleus and shortening of the lateral chain transforming an highly insoluble and immiscible molecule in an hydrophilic and detergent one. Congenital defect of one of the enzymes of bile acid synthesis (26-alpha-hydroxylase) constitutes the etiology of cerebrotendinous xanthomatosis, associating degenerative disease of the central nervous system, cutaneous xanthomas and cataract; the degenerative process may be stopped by a substitutive therapy with chenodeoxycholic acid. In another syndrome characterised by a lack of peroxisomes (Zellweger disease and associated syndromes), some bile acid metabolites accumulate due to the enzymatic block. Some cases of malabsorption due to a congenital defect of bile sterol synthesis are reported; such a case was jointly investigated in Brussels and Groningen.

Central Nervous System Diseases↗

Effect of selenium supplementation on thyroid hormone metabolism in an iodine and selenium deficient population.

OBJECTIVE: Severe selenium deficiency has been documented in northern Zaïre, already known as one of the most iodine deficient regions in the world and characterized by a predominance of the myxoedematous form of cretinism. This has been attributed to the double deficiency of essential trace elements. A short selenium supplementation programme was conducted in this area to evaluate the effects of a selenium supplementation on thyroid diseases. DESIGN: Placebo or selenium 50 micrograms as selenomethionine was administered once daily for 2 months. Blood and urine samples were collected before and after supplementation. PATIENTS: Fifty-two healthy schoolchildren from northern Zaire. MEASUREMENT: Selenium status, thyroid function and urinary iodide were determined. RESULTS: After 2 months of selenium supplementation, mean +/- SD serum T4 decreased from 73.1 +/- 45.4 to 48.3 +/- 23.7 nmol/l (P less than 0.001), serum FT4 from 11.8 +/- 6.7 to 8.4 +/- 4.1 pmol/l (P less than 0.01), and serum rT3 from 124 +/- 115 to 90 +/- 72 pmol/l (P less than 0.05), without significant change in serum T3 and serum TSH. CONCLUSION: Deiodinase type I which has been shown to be a seleno-enzyme could account for the changes in thyroid hormones in our subjects. Our data show that selenium plays a definite role in thyroid hormone metabolism in humans. Selenium could be an important cofactor in the clinical picture of iodine deficiency in Central Africa and could be involved in the aetiology of both forms of cretinism.

Administration, Oral↗

Effect of selenium supplementation in hypothyroid subjects of an iodine and selenium deficient area: the possible danger of indiscriminate supplementation of iodine-deficient subjects with selenium.

Selenium and seleno dependent glutathione peroxidase (GPX) deficiency has been described in endemias of myxedematous cretinism. In northern Zaire, a selenium supplementation trial has been conducted. Beside correcting the GPX activity, two months of selenium supplementation was shown to modify the serum thyroid hormones parameters in clinically euthyroid subjects and to induce a dramatic fall of the already impaired thyroid function in clinically hypothyroid subjects. These results further support a role of selenium in thyroid hormone metabolism. In an iodine deficient area, this selenium deficiency could lead to opposite clinical consequences: protect the general population and the fetus against iodine deficiency and brain damage; and in turn, favour the degenerative process of the thyroid gland leading to myxoedematous cretinism.

Child↗

The respective effects of serum thyroxine and triiodothyronine on serum thyrotropin and lipid parameters in endemic juvenile hypothyroidism.

The respective effects of serum total T4 concentration and of serum total T3 concentration on serum TSH concentration and on lipid parameters were compared in 84 7- to 16-year-old children of the Northern Zaire goitre endemia classified in group A (T4 greater than 77 nmol/l and T3 greater than 1.69 nmol/l), B (low T4, normal T3) and C (low T4, low T3). Mean serum TSH level was normal in group A (2.3 mU/l), it raised to 39.4 mU/l in group B (p less than 0.001) and to 166.3 mU/l in group C (p less than 0.001 vs A and B). Low density lipoprotein cholesterol and apoprotein B were increased in group B vs A (p less than 0.05) and in group C vs A (p less than 0.001) and B (p less than 0.001 for apoprotein B; not significant for cholesterol). High density lipoprotein cholesterol and apoprotein A1 were similar in the three groups. Mean serum triglyceride level, not different in groups A and B, was doubled in group C (p less than 0.001). Multiple regression analysis showed that serum TSH, apoprotein B, and triglyceride levels were influenced by both thyroid hormones concentrations with a predominant effect of serum T4 on the first two parameters and of serum T3 on the last one. In conclusion, low serum T4 with normal T3 concentrations resulted in an increase in serum TSH and in an altered lipid metabolism; it clearly represented an hypothyroid state.

Adolescent↗

Role of vitamin E in the protection of the resident macrophage membrane against oxidative damage.

The variation in tocopherol content of resident peritoneal rat macrophages was investigated during an oxidative stress provided by superoxide anions. Fluorometric measurements showed that phagocytic cells contain 298 +/- 18 ng vit.E/mg prot. The vitamin E level remains nearly constant during 1 h of incubation: 266 +/- 46 ng vit.E/mg prot. HPLC control at 37 degrees C validates our fluorometric measurement. Superoxide anions (O2-.) synthesis was activated by phorbol myristate acetate (PMA) (0.5 microgram/ml), after 1 h of incubation a decrease of 40% of the macrophage tocopherol level was observed and assessed by HLPC control. No tocopherolquinone (TQ) was detected. To clarify this point, tocopherol oxidation was followed spectrophotometrically. Results did not show any appearance of TQ at 265 nm but appearance of a peak at 307 mm. This our results show for the first time that macrophages possess vitamin E which plays a partial role in the protection of their plasma membrane. The lack of detection of TQ is of interest and the study of this unidentified product of oxidation should help us to understand the exact metabolism of vitamin E.

Animals↗

Studies on a focus of yaws in Ubangi, Zaire.

Yaws (buba, Frambösie, pian), a non-venereal treponematosis of skin and bones is a tropical disease that affects primarily children. Eradication programs launched between 1950 und 1970 reduced the incidence substantially; resurgences, however, have been reported from several countries. We have studied a geographically isolated focus of yaws in the Ubangi area of northwestern Zaire. In survey I, in 1981, of the 4.407 participants from 11 villages, 348 (7.9%) had active lesions of yaws. All patients and their contacts were treated immediately with benzathine penicillin G. In survey II, in 1982, in 6 of the previously studied villages, of 5,390 participants, 136 (2.5%) had active lesions of yaws. In 1981, the predominance of primary lesions (86%) and high numbers of patients in all age groups, with the highest prevalence (23.4%) in children 10-14 years of age, suggest that yaws recently recurred at this focus. In 1982, only 25.7% of the lesions were primary and the highest prevalence (6.5%) had shifted to the younger age group of 5-10 years-old. In survey I more males (63%) were infected in the age group 0-24 years, and more females (89%) in those over 40 years. In survey II, more males (61.3%) were infected in the age group 0-14 years, and only females (100%) in the age groups 25 years and older. Seventy-one percent (1981) and 86% (1982) of the initial lesions were on the lower limbs. Participation of the population in survey I was 41.7% and was greatest (62%) in the locality where there was a newly established dispensary. In survey II, participation rose to 73.8%. Areas adjacent to the focus of yaws with longstanding dispensaries were free of yaws.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Erythrocyte vitamin E is oxidized at a lower peroxide concentration in neonates than in adults.

Erythrocytes of neonates and adults were incubated with increasing concentrations of H2O2 in the presence of a catalase inhibitor and in the absence of glucose; the pattern of oxidation of vitamin E was analyzed in relationship to that of glutathione, hemoglobin, and polyunsaturated fatty acids (PUFA), and in relationship to hemolysis. The changes of these various parameters were analyzed in function of H2O2 concentration and in relation to incubation time, and were compared in erythrocytes from neonates and adults. In the absence of H2O2, erythrocyte glutathione and tocopherol levels were similar in neonates and adults, despite fourfold lower serum vitamin E level in neonates; alpha-tocopherolquinone, methemoglobin, and malonyldialdehyde (MDA) were not detectable. At 0.375 mmol/L of H2O2, glutathione was completely oxidized. Erythrocyte alpha-tocopherol remained unchanged up to 0.75 mmol/L of H2O2, then decreased linearly, with increasing H2O2 concentrations to 10% of its initial value at 1.5 mmol/L of H2O2 in erythrocytes from neonates, whereas those from adults required 2.0 mmol/L of H2O2 (P less than .05) for the same level of oxidation. The formation of alpha-tocopherolquinone appeared inversely related to the decrease of alpha-tocopherol. The incubation time did not influence the level of vitamin E oxidation. MDA was generated autocatalytically and resulted in hemolysis at 1.5 mmol/L of H2O2 in erythrocytes from neonates and at 3.5 mmol/L of H2O2 in erythrocytes from adults (P less than .001). After four hours of incubation, MDA reached a plateau at a greater level (365 +/- 46 nmol/L) in cells of neonates than in those of adults (208 +/- 37 nmol/L/mL) (P less than .001). Hemoglobin was oxidized in the same pattern in erythrocytes of neonates and adults, and 90% of it was oxidized at 0.625 mmol/L of H2O2. In conclusion, in the experimental conditions used, oxidation of glutathione precedes that of vitamin E, and tocopherol is the last antioxidant to be consumed before the autocatalytic generation of MDA. Differences in the pattern of vitamin E oxidation, MDA generation, and hemolysis in erythrocytes from neonates and adults may be due to a lower erythrocyte vitamin E-PUFA ratio in neonates.

Adult↗

Endemic infantile hypothyroidism in a severe endemic goitre area of central Africa.

Thyroid function and exposure to dietary goitrogenic factors (iodine deficiency and thiocyanate overload) were studied at birth and from birth to 7 years in 200 neonates and 347 children living in the severe endemic goitre area of Ubangi, Northern Zaire. Serum T4 was at the lower limit of normal at birth (104 +/- 4 nmol/l) and stayed at that level during the first year of life (123 +/- 9) (NS), but decreased to 75 +/- 8 (P less than 0.001) at 2-4 years and to 62 +/- 6 (P less than 0.001) at 5-7 years of age. Mean serum FT4 decreased from 10.4 +/- 0.9 pmol/l during the first year to 8.2 +/- 1.0 (NS) at 2-4 years (NS) and to 7.7 +/- 0.9 (P less than 0.05) at 5-7 years. Mean serum TSH was 10.4 (8.4-12.9) mU/l (geometric mean +/- 1 SEM) during the first year, 10.1 (7.5-13.7) (NS) at 2-4 years and 24.3 (18.5-31.9) (P less than 0.05) at 5-7 years. Mean serum T3 was 3.23 +/- 0.12 nmol/l during the first year and remained stable thereafter. The frequencies of low T4 (T4 less than 77 nmol/l), high TSH TSH (TSH greater than 50 mU/l), and low T4 and T3 (T3 less than 1.69 nmol/l) were twice as high at 5-7 years as in the first year (respectively 65%, 42% and 15%). The urinary iodide concentration of the children was stable and low throughout the study period. By contrast, serum thiocyanate concentration which was high at birth (129 +/- 5 mumol/l) decreased to normal values between 3 and 12 months of age and increased again during and after weaning (1 to 3 years of age) to reach a value of 138 mumol/l which was comparable to that observed in adults in the same area. Thiocyanate concentration was high (133 +/- 7 mumol/l) in the mothers' serum but low in the mothers' milk (57 +/- 3 mumol/l) (P less than 0.001). Multivariate analysis showed that both iodine deficiency and thiocyanate overload were explanatory factors of the serum levels of T4, FT4 and TSH in children. In conclusion, our results show that infantile hypothyroidism is much more frequent at 5-7 years of age than at birth or during the first year of life. The deterioration in thyroid function during and after weaning is linked to persistent iodine deficiency accompanied by an increase in thiocyanate overload. The variability in the age of onset, the severity, and the duration of infantile hypothyroidism might explain the wide range of psychomotor and physical abnormalities observed in a large proportion of subjects in this area.

Adolescent↗

Effects of selenium supplementation on thyroid hormone metabolism in phenylketonuria subjects on a phenylalanine restricted diet.

Type I 5'-deiodinase was recently characterized as a selenocysteine-containing enzyme in humans and other mammals. Up to now, the effect of selenium (Se) supplementation on thyroid hormone metabolism in humans has only been reported in the very peculiar nutritional environment of Central Africa, where combined severe iodine and Se deficiency occurs. In this study, a group of phenylketonuria subjects with a low selenium status, but a normal iodine intake were supplemented with selenium to investigate changes in their thyroid hormone metabolism. After 3 wk of selenium supplementation (1 microgram/kg/d), both the concentrations of the prohormone thyroxine (T4) and the metabolic inactive reverse triiodothyronine (rT3) decreased significantly. Clinically, the phenylketonuria subjects remained euthyroid before and after selenium supplementation. The individual changes of plasma Se and glutathione peroxidase activity were closely associated with individual changes of plasma T4 and rT3.

Adolescent↗