Bernard Contempre

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

OBJECTIVE Severe selenlum 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.

Right ventricular dysfunction in septic shock: assessment by measurements of right ventricular ejection fraction using the thermodilution technique.

Right ventricular ejection fraction (RVEF) was measured by the thermodilution technique in a scries of 127 consecutive critically ill patients monitored with a modified pulmonary artery (PA) catheter equipped with a fast response thermistor. Thermodilution RVEF was significantly lower in septic shock (23.8 8.2%, 93 measurements) than in sepsis without shock (30.3 10.1%, 118 measurements) or in the absence of sepsis or cardiopulmonary impairment (32.5 7.1%, 62 measurements). Both myocardial depression and pulmonary hypertension could account for this impairment of RV function. RVEF decreased from 35.1 9.8 to 24.2 10.4% (P < 0.01) during development of septic shock and increased from 25.0 7.6 to 29.8 8.5%, (P < 0.05) during recovery (14 patients). Initial RVEF in septic shock was 27.8 8.6% in 11 patients who survived but only 20.9 6.7% (P < 0.02) in the 23 patients who eventually died. Thus, RV dysfunction is common during septic shock, is directly related to its severity, and can easily be recognized in patients monitored with a PA catheter.

Selenium and the thyroid: how the relationship was established.

Several hypotheses concerning consequences of selenium deficiency on iodine metabolism can be proposed on the basis of experimental studies in rats and from epidemiological and experimental studies in humans. By decreasing intracellular GSH peroxidase activity, selenium deficiency may increase hydrogen peroxide (H2O2) supply and lead over several weeks to the thyroid atrophy observed in myxoedematous cretins. By improving thyroid hormone synthesis and by decreasing peripheral thyroxin (T4) deiodination, selenium deficiency could protect fetal brain T4 supply and thus prevent neurologic cretinism. Selenium deficiency may protect against iodine deficiency by decreasing T4 metabolism--and thus iodide leakage and--perhaps also by increasing H2O2 supply and thyroid hormone synthesis and thus thyroid efficiency.

Selenium deficiency and thyroid fibrosis. A key role for macrophages and transforming growth factor beta (TGF-beta).

Free radical damage and fibrosis caused by selenium deficiency are thought to be involved in the pathogenesis of myxoedematous cretinism. So far, no pathway explains the link between selenium deficiency and tissue fibrosis. Pharmacological doses of iodine induce necrosis in iodine-deficient thyroids. Necrosis is much increased if the glands are also selenium-deficient, which then evolve to fibrosis. This rat model was reproduced to explore the role of selenium deficiency in defective tissue repair. At first, proliferation indexes of epithelial cells and fibroblasts were comparable between selenium-deficient and control groups. Then, in selenium-deficient thyroids the inflammatory reaction was more marked being mainly composed of macrophages. The proliferation index of the epithelial cells decreased, while that of the fibroblasts increased. These thyroids evolved to fibrosis. TGF-beta immunostaining was prominent in the macrophages of selenium-deficient rats. Anti TGF-beta antibodies restored the proliferation indexes, and blocked the evolution to fibrosis. In selenium deficiency, an active fibrotic process occurs in the thyroid, in which the inflammatory reaction and an excess of TGF-beta play a key role.

Iodine deficiency, other trace elements, and goitrogenic factors in the etiopathogeny of iodine deficiency disorders (IDD)

Severe goiter, cretinism, and the other iodine deficiency disorders (IDD) have their main cause in the lack of availability of iodine from the soil linked to a severe limitation of food exchanges. Apart from the degrees of severity of the iodine deficiency, the frequencies and symptomatologies of cretinism and the other IDD are influenced by other goitrogenic factors and trace elements. Thiocyanate overload originating from consumption of poorly detoxified cassava is such deficiency. Very recently, a severe selenium deficiency has also been associated with IDD in the human population, whereas in animals, it has been proven to play a role in thyroid function either through a thyroidal or extrathyroidal mechanism. The former involves oxidative damages mediated by free radicals, whereas the latter implies an inhibition of the deiodinase responsible for the utilization of T4 into T3. One concludes that:1.Goiter has a multifactorial origin2.IDD are an important public health problem; and3.IDD are a good model to study the effects of other trace elements whose actions in many human metabolisms have been somewhat underestimated.

Transthoracic electrical bioimpedance versus thermodilution technique for cardiac output measurement during mechanical ventilation

To study the possible influence of mechanical ventilation on the accurracy of thoracic electrical bioimpedance (TEI) in the measurement of cardiac output, we determined cardiac output concurrently by TEI using Kubiceks equation and by thermodilution in 8 acutely ill patients who were mechanically ventilated (assist/control mode) but who had no underlying respiratory failure. Cardiac outputs were lower with TEI than with thermodilution (3.97±0.80 vs 4.83±1.16 l/min p=0.004) and there was poor correlation between the values (r=0.41). Although there is a need to develop non-invasive techniques to measure cardiac output, the present study indicates that TEI is not reliable in mechanically ventilated patients.

Cretinism, thyroid hormones and selenium

The effect of angiotensin II on cytosolic free Ca 2+ ion concentrations ([Ca 2+ ] i ) were studied in single porcine granulosa cells using the calcium-sensitive fluorescent dye fura-2 and high temporal resolution fluorescent videomicroscopy. Angiotensin II initiated specific, rapid, transient and topographically organized increases in [Ca 2+ ] i in a subpopulation of single swine granulosa cells

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 Bandundu 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 μg/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.

Bretylium tosylate versus lidocaine in experimental cardiac arrest

Bretylium tosylate has been shown effective in the treatment of ventricular fibrillation and in the prevention of its recurrence. However, lidocaine is generally preferred because bretylium could have adverse hemodynamic effects related to its antiadrenergic action. To explore further the differences between these two antiarrhythmic agents, the authors compared the effects of bretylium, lidocaine, and saline on a standardized dog model of ventricular fibrillation followed by electromechanical dissociation (EMD). The protocol included three successive episodes of cardiac arrest in each animal. Three minutes before each episode of ventricular fibrillation, 5 mg/kg of bretylium tosylate (n = 11), 1 mg/kg of lidocaine (n = 9) or saline (n = 12) were administered blindly. There was no difference in the duration of cardiac arrest (bretylium, 8 min 18 sec; lidocaine, 7 min 54 sec; saline, 8 min 20 sec) or the total doses of epinephrine required to resuscitate the animals. Both bretylium and lidocaine appeared to preserve cardiac function 5 minutes after recovery, as stroke volume increased from 17.8 +/- 6.7 to 18.7 +/- 6.7 mL (NS) after bretylium and from 17.7 +/- 7.7 to 19.0 +/- 7.0 mL (NS) after lidocaine, but decreased from 19.0 +/- 5.3 to 14.6 +/- 6.0 mL (P less than .05) after saline. During the first 10 minutes of EMD, ventricular fibrillation or ventricular tachycardia recurred in 4 dogs treated with lidocaine, 3 dogs treated with saline, but no dog treated with bretylium (P less than .05 between bretylium and saline).(ABSTRACT TRUNCATED AT 250 WORDS)

Right ventricular function in septic shock

In critical states, right ventricular (RV) function is commonly altered by an increase in RV afterload or a depressed contractility. Severe sepsis can be associated with both. RV afterload can be increased by the pulmonary hypertension related to the release of various mediators and the development of microthrombi in the pulmonary circulation [1, 2]. Myocardial depression is also a relatively early event in the course of septic shock, even when cardiac output is normal or elevated [3, 4]. The release of circulating substances, various metabolic disorders, myocardial edema and decreased coronary perfusion have been incriminated [4]. Recent studies have well demonstrated that left ventricular ejection fraction could be depressed early during septic shock [3]. Right ventricular dysfunction might be more severe than left ventricular dysfunction, since the left ventricular afterload is typically reduced while RV afterload is usually increased (Fig. 1). Measurements of right ventricular ejection fraction (RVEF) have been recently available at the bedside by the thermodilution technique and could represent an additional parameter that can be routinely measured. RVEF values obtained by the thermodilution technique correlate well with those obtained by other techniques [58].