Oxidative and antioxidative factors in the serum of thyroid cancer patients treated with 131I.

The variation of some parameters involved in maintaining the balance between pro- and anti-oxidative factors was followed-up in a group of patients thyroidectomized for folliculo-papillary, papillary and follicular cancer, before and after 5 days following the 131I administration. Radiotherapy led to the intensification of lipid peroxidation expressed by a significant increase in the malondialdehyde values. Among the parameters involved in the antioxidative process we noted an increase in both SH nonprotein groups and ceruloplasmin concentration. The total antioxidative capacity lowered significantly following irradiation, whereas uric acid remained unaltered.

The changes of peroxides and total antioxidants in the plasma of patients who received 131I therapeutically.

Fifty patients with thyroid cancer were studied during administration of high doses of 131I (5-50 mCi). Peroxides, total antioxidants and free sulphydryl-groups were measured in the blood samples obtained before and after administration of radioactive iodine. After the administration of iodine, significant increases of peroxides and free SH groups were observed, as well as the decrease of total antioxidants. These biochemical changes were in agreement with significant decreases of blood platelets and lymphocytes. The data obtained brought forward again the much debated problem of peroxidation and antioxidants in cancer, since comparatively, the patients with other localizations of tumors presented decreases of peroxides and variable amounts of antioxidants. The influence of iodine and thyroid hormones is discussed, with reference to a previous paper in which high levels of peroxides had been found both in hyper- and in hypothyroidism but with different mechanisms. The biochemical changes observed in the patients treated with radioactive iodine confirmed the involvement of peroxides in the consequences of internal irradiation.

Growth hormone (GH) release by arginin-vasotocin (AVT) given intranasally in sexually immature children.

Eighteen healthy children were given 50 micrograms synthetic AVT intranasally and samples of serum for GH, magnesium and alpha-amino-nitrogen were drawn 30, 60 and 120 minutes later. There was a significantly different mean of GH peak level (13.1 +/- 3.02 microU/ml) which occurred generally at 30 minutes. The number of GH responders (i.e. peak level greater than 15 microU/ml) was of 7/18. The means of chemical determinations elicited little though opposite changes: slight increases in magnesium and slight decrease in alpha-amino-nitrogen. In a separate day, a sleep test of 30 minutes-duration performed in the morning resulted in a significantly greater GH peak level (28.2 +/- 9.7 microU/ml) but the number of GH responders was nearly the same (6/18). The serum magnesium levels following sleep decreased slightly and unsignificantly. The involvement of serotonergic neurons in mediating GH-releasing effects of AVT is briefly discussed.

Thyroid hormone-induced reduction of urinary 5-hydroxyindole acetic acid (5 HIAA) in obese children. Comparison with hypothyroid patients of similar age having either pituitary dwarfism or congenital myxedema.

Urinary excretion of monoamine metabolites (noradrenaline-NA, adrenaline-A, 3-methoxy-4-hydroxyphenyl glycol-MHPG, homovanillic acid-HVA, 5-hydroxyindole acetic acid-5 HIAA) was studied in four groups of children as follows: Group I consisting of obese children subjected to caloric restriction and to a short term course of thyroid extract in "low" dosage (1-2 mg/kg bwt), Group II consisting of obese children subjected to diet alone, Group III consisting of children myxedema and subjected to a short term course of thyroid extract given in the "high" dosage (3-5 mg/kg bwt) and Group IV consisting of GH deficient short children having (many of them) thyrotropin deficiency and subjected to a short term course of thyroid extract in "very high" dosage (5-10 mg/bwt). In obese, calorie-restricted children, the previously low mean level of 5 HIAA excretion was further lowered by thyroid extract. In obese children subjected to calorie restriction alone no urinary abnormality was noted. The congenitally hypothyroid patients had low levels of basal 5 HIAA when compared to controls. The degrees of 5-hydroxy tryptamine (5 HT) deficiency in Group III was similar to the obese groups. The thyroid extract course did not influence, at least in short term administration, the low 5 HIAA levels in group III. In GH deficient, short children (group IV) thyroid extract had no significant effect on urinary pattern of monoamine metabolites. A central 5 HT deficiency may tentatively explain the mood disturbances and possibly the other psychic disorders in both the obese and myxedematous patients. The different effects of thyroid extract on 5 HIAA may also witness the differences in the food intake behaviour in these two conditions.

Significance of high levels of serum malonyl dialdehyde (MDA) and ceruloplasmin (CP) in hyper- and hypothyroidism.

The lipid peroxidation process is enhanced in both hyperoxygenated or underoxygenated tissues though its mechanism of production is different. Because in thyroid functional diseases there are severe disorders in tissue oxygenation we studied the lipid peroxidation process by using the serum level of malondialdehyde (MDA) as indicator. We also determined the serum ceruloplasmin (CP), an enzymatic protein belonging to the circulating system of antioxidative protection and also playing a role in the cell-mediated immunity. We also followed serum level of uric acid (UA). The determinations were performed on serum samples collected from three groups: 1, adult control subjects: 2. adult untreated hyperthyroid patients, and 3. adult hypothyroid thyroidectomized patients to whom replacement therapy was discontinued for at least 15 days. The mean MDA level was significantly higher in both hyperthyroid and hypothyroid patients by comparison to the control group. CP mean level was significantly lower than in controls. It was concluded that in post thyroidectomy hypothyroidism an enhancement of lipid peroxidation does exist and that its consequences are probably aggravated by the low serum CP level. The enhancement of the process occurs by other mechanisms than for hyperthyroid group. At hypothyroid patients there is an ADP excess which is degenerated to xanthine, the substrate of xanthine oxidase resulting in toxic anion superoxide and UA. In contrast with hyperthyroid group, in hypothyroid patients we observed significant higher values of UA in comparison to the controls. The excess of MDA found in hyperthyroid patients is statistically significant, but its consequences are probably less severe because the serum CP is higher than normal, a rather expected finding for an autoimmune disease.

Serum-to-saliva transfer of the immunoreactive insulin (IRI) in children with obesity associated with insulin-resistance.

Assuming that the serum-to-saliva transfer of insulin reflects internalization and re-cycling of the hormone in the membrane-located binding sites of salivary epithelial cells and that these cells have in obesity a'marked decrease in insulin receptor content, it has been postulated that insulin resistance in infantile obesity can be detected by the changes in the salivary immunoreactive insulin during the oral glucose tolerance test (OGTT). The study included 31 obese children and adolescents of both sexes, subjected to OGTT. Samples of blood and saliva were collected at 30, 60, 120, 180 and 240 minutes for determinations of glucose and IRI. The blood glucose values were generally normal whereas IRI was excessively high. The dynamics of salivary IRI was similar (easy peak followed by slow descent) with the mean serum values but lower by about two-thirds, and the peak was 30-60 minutes delayed. The serum IRI values correlated significantly with the saliva ones at all time-intervals except for the 30-minute ones. The serum IRI values were significantly lower at the 30-minute time interval, whereas the salivary IRI were the lowest (and of borderline significance) at the 60-min. time interval. The mean glucose/kg doses given orally were not significantly different in the two groups. It was concluded that a hormonal activity detectable by IRI assay through the PEG separation method does exist, with a concomitant variation of serum-to-saliva transfer as shown by the OGTT test. It was also concluded that since the salivary values are lower, the direction of the flow is from serum to saliva and not the reverse. Finally, on the basis of our data, an "in situ" synthesis of insulin (hormonogenic exocrinism) can not be ruled out.

Determination of urinary mucopolysaccharides in Graves' disease.

Urinary mucopolysaccharides (u MPZ) were determined in 114 patients with thyroid diseases. The values were elevated in 95.8% of patients with Graves' disease with infiltrative ophthalmopathy, and in 66.6% of patients with Graves' disease without clinically manifest infiltrative ophthalmopathy; in the second group of patients we consider that there is a subclinical infiltrative ophthalmopathy. In conclusion, the determination of u MPZ can be considered as a criterion for the diagnosis of Graves' disease in patients with hyperthyroidism without clinically manifest infiltrative ophthalmopathy; in a number of these cases, infiltrative ophthalmopathy may become clinically manifest. For that reason, increased u MPZ can represent a criterion for an eventual delay of an ablative therapy in Graves' disease. It is not a significant statistic difference (p greater than 0.1) between the values of u MPZ in patients with Graves' disease with clinically manifest ophthalmopathy and in those with subclinical infiltrative ophthalmopathy. The thyroid functional status does not influence in any way the values of u MPZ (p greater than 0.1). There is no correlation between the degree of eye protrusion and the values of u MPZ (r = = -0.05)

The dyslipemic syndrome in acromegaly.

The clinico-hormonal course of acromegaly and the presence of the hyperlipemic syndrome were studied in relation to age, sex, associated hypothyroidism, diabetes, obesity and cardiovascular and atherosclerotic complications in 43 acromegalic patients (18 males and 25 females) of which 6 had received no treatment and 37 had been submitted 2 - 13 years to conventional roentgentherapy (31 cases), 90Y (5 cases) and hypophysectomy (1 case). Hyperlipemia (HLP), present in 24 acromegalic patients (55.8% of the cases) unrelated to age, was more frequent in women (64% as against 44% in males) and correlated with the clinico-hormonal evolution (GH greater than 20 mg) (60% of the cases), and associated hypothyroidism (79%), obesity (42%) and diabetes (25%). Of the hyperlipemic acromegalic patients, 62% had cardiovascular and atherosclerotic complications. The results of the study point to the need for a hypoglucidic, hypolipidic and associated treatment for hypothyroidism, diabetes and obesity in the prophylaxis of acromegalic atherosclerosis.

The antagonism between pineal peptides and catecholamines. I. The action of the pineal peptide extract on some effects of exogenous adrenaline in the rat.

The effects of adrenaline alone or associated with Crinofizin, a pineal polypeptide extract, were studied on rats. The drug given 15 minutes before a hyperglycemic adrenaline dose counteracted the pharmacologic effects with lethal consequences of catecholamine as well as certain metabolic effects such as elevation of blood levels of glycerol, phospholipids and cholesterol. Post-adrenaline hyperglycemia was not reduced by Crinofizin under the given experimental circumstances. The glycogenolytic effect of adrenaline was slightly inhibited.

The effect of combined administration of L-proline and glycine on GH and IRI release in healthy prepuberal children.

Proline (100 mg/kg b.w.) was given per os and after 30 minutes 10% glycine was i.v. injected to 25 healthy children of both sexes. A positive response (an increase of over 5 ng/ml of serum level of GH) was found in 21 of the 25 children. The insulin test showed a positive response in 24 of the 25 children. It was concluded that the decrease in glycine dosage from 250 mg/kg b.w. (earlier reports by the same authors) to 100 mg/kg b.w. (present data) is generally compensated by l-proline priming. The IRI serum levels were almost unchanged. By l-proline priming, the glycine test can also be applied to subjects with body weight over 40 kg, in doses of 100 mg/kg b.w. for exploring the secretory reserve of the somatotropic axis.

Changes in plasma lipids in hirsute women.

The changes in blood cholesterol, triglycerides, total lipids and lipoproteinograms were examined in 40 women with hirsutism compared to 40 normal women of similar ages as control. The results show a significant increase in cholesterol, triglycerides and total lipids in hirsutism. The lipoproteins, analysed according to Frederickson's classification show that while only 12% of the normal women came within type II A, in hirsutism the proportion was 50%. A proportion of 5% of normal women came within type II B whereas in hirsutism there were 28%. In conclusion, both types of blood lipoprotein alteration with atherogenic potential are significantly better represented in hirsutism cases.

Cardiovascular pathology in acromegaly and some effects of the 90 yttrium implant in the hypophysis.

Examination of the cardiovascular apparatus (cv) of 25 acromegalic patients revealed an increased incidence of cardiovascular pathology as against normal individuals. Acromegalic patients with arterial hypertension (AH) show a twice higher incidence of ischemic cardiopathy, cardiomegaly with obvious or latent cardiac failure, arrhythmias, which frequently lead to death. The uncertain pathogeny of cardiomyopathy implied: hypoxia due to heart hypertrophy (over 500 g and increased cross-section of the fibre to over 26/mu), adrenergic deficiency resulting from increased protein synthesis and decrease in thyrosine, a precursor of myocardic cathecolamines. The increased incidence of coronary pathology is favoured in acromegalic patients by diabetes, hyperlipoproteinemia, low endogenous heparin, increased ureic acid and platelet adhesivity. Hypophysectomy by hypophysolysis (20 cases) brings relief and cures cardiovascular pathology, reduces AH, corrects the coronary risk factors, cures hypophyseal diabetes. The existence of AH and cardiovascular pathology is an indication for surgical treatment in evolutive acromegaly.

The effect of thiazolidin carboxylic acid (ThCA) on the redox equilibrium maintaining in the rat hepatocyte with streptozotocin-induced diabetes.

The variation of the activities of glutathion peroxidase, glutathion reductase, glucose-6-phosphate dehydrogenase, as well as of the concentrations of lipid peroxides and -SH groups of nonproteic nature, was followed up in the hepatocyte of normal rats, of those with, streptozotocin-induced-diabetes, and of diabetic rats treated with thiazolidin carboxylic (ThCA) acid. Free peroxides and glutathion peroxidase were increased in the diabetic animals as against the normals, whereas glutathion reductase, glucose-6-phosphate dehydrogenase and the -SH groups of nonproteic nature had lower values. A return to normal of these parameters was noticed in the animals treated with ThCA.

Biosynthesis and operating mechanism of estrogens in ovariectomized animals under the effect of -SH groups.

This paper is part of a series aimed to investigate the mechanism of the action of Folcysteine, a substance that has the capacity to release in the body active -SH groups and has been proved to be effective in the control of menopausal troubles. As an experimental model the ovariectomized rat, rather similar, from the viewpoint of the hormonal balance, to the aged female, has been considered. Under these conditions, the effect, at the uterine and adrenalian level of the treatment with two different doses of estradiol with Folcysteine alone as well as associated with estradiol, has been investigated. Our results indicate that the active -SH groups released by Folcysteine intensify the effect of estrogens upon the uterine tissue and stimulate the estrogen biosynthesis at adrenalian level.