THE GOITROGENIC EFFECT OF NATURALLY OCCURRING L-5-VINYL- AND L-5-PHENYL-2-THIO-OXAZOLIDONE IN RATS

1966 ◽  
Vol 53 (2) ◽  
pp. 342-352 ◽  
Author(s):  
F-E. Krusius ◽  
Pentti Peltola
Keyword(s):  
Endemic Goitre ◽  
Control Series ◽  
Radioiodine Uptake ◽  
Clear Cut ◽  
Naturally Occurring ◽  
Term Administration ◽  
Uptake Test ◽  
Rat Thyroid ◽  
Oral Doses

ABSTRACT L-5-vinyl-2-thio-oxazolidone (VTO), found in the seeds of cruciferous weeds and in milk specimens from the endemic goitre districts of Finland, was fed to rats. A dose of 0.1 μg/day had an almost significant and of 0.5 μg/day a significant weight-increasing effect on the thyroid in 1—15 weeks. The quantities of VTO found in milk specimens from endemic goitre districts of Finland are greater than the concentration of VTO in drinking fluid necessary for producing enlargement of the thyroid in rats. The minute daily oral doses of VTO that led to enlargement of the thyroid did not inhibit the radioiodine uptake of the gland. The smallest single oral dose of VTO which inhibited the 4-h radioiodine uptake in the rat thyroid was 0.1 mg (almost significant) and 0.5 mg (significant), i. e. about 1000 times greater than the smallest daily amount which produced thyroid enlargement in long-term administration. The inhibition seemed to last for less than 8 hours. The goitrogenic activity of milk to which VTO had been added was still present after storage for one day, though VTO was no longer demonstrable by the chemical method of assay generally employed. L-5-phenyl-2-thio-oxazolidone (PTO), a compound also occurring naturally in weeds of the Cruciferae family, when administered to rats in doses as low as 2 μg/day in long-term experiments, caused a distinct increase in relative thyroid weight, which appeared from 1 to 9 weeks after the start of the experiments. In the radioiodine tests, there were no clear-cut differences as compared with the control series. The results with both compounds show that the inhibition in the radioiodine uptake test after a single dose is too insensitive a method for the detection of minute amounts of goitrogens with a thiouracil-type of activity in foodstuffs.

scholarly journals Effects of Total Thyroid Ablation Versus Near-Total Thyroidectomy Alone on Mild to Moderate Graves’ Orbitopathy Treated with Intravenous Glucocorticoids

2007 ◽  
Vol 92 (5) ◽  
pp. 1653-1658 ◽  
Author(s):  
Francesca Menconi ◽  
Michele Marinò ◽  
Aldo Pinchera ◽  
Roberto Rocchi ◽  
Barbara Mazzi ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Total Thyroidectomy ◽  
Outcome Measure ◽  
Randomized Study ◽  
Radioiodine Uptake ◽  
Main Outcome Measure ◽  
Thyroid Ablation ◽  
Graves Orbitopathy ◽  
Uptake Test

Abstract Context: Graves’ orbitopathy (GO) is probably caused by autoimmune reactions against autoantigen(s) shared by thyroid and orbital tissues sustained by intrathyroidal autoreactive T-lymphocytes infiltrating the orbit. Total thyroid ablation (TTA) may be beneficial for GO through removal of shared antigen(s) and autoreactive T-lymphocytes, but randomized studies are lacking. Objective: Our objective was to evaluate the effects of TTA in patients with GO treated with iv glucocorticoids (GC). Design/Setting: A prospective, single-blind, randomized study was conducted at a referral center. Patients/Interventions: Sixty patients with mild to moderate GO were randomized into: 1) near-total thyroidectomy (TX); or 2) TX plus 131I (TTA) groups, and then treated with iv GC. Patients were evaluated 3 and 9 months after iv GC. Main Outcome Measure: Overall improvement of GO at 9 months was the main outcome measure. Results: The distribution of GO outcome at 9 months was significantly more favorable in TTA than in TX patients (P = 0.0014 by χ2 test). A cumulative significant (P = 0.0054) difference between the two groups at 3 and 9 months was found using a generalized linear model. Radioiodine uptake test and thyroglobulin assay in a patient sample showed complete ablation in the majority of TTA, but not of TX patients. Conclusions: Compared with thyroidectomy alone, TTA is followed by a better outcome of GO in patients given iv GC. Whether TTA maintains this advantage in the long-term remains to be established.

Comparative Benefits of the Non-Human Primate in Long-Term Toxicity Studies with Iron Chelators: 12-Month Studies with Deferiprone.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3785-3785
Author(s):  
John Connelly ◽  
Michael Spino ◽  
Fernando Tricta
Keyword(s):  
Body Weight Gain ◽  
Clinical Signs ◽  
Plasma Chemistry ◽  
Iron Chelators ◽  
Iron Loading ◽  
Oral Toxicity ◽  
Cynomolgus Monkeys ◽  
Term Administration ◽  
Oral Doses

Abstract Cynomolgus monkeys and rats have been the species of choice for evaluation of general toxicity during the non-clinical development of iron chelators. Each model has its advantages in safety assessment studies, although the relatively poor conservation of iron in rats and other differences in their iron handling compared with primates, including man, have raised questions about their appropriateness. It was reported that in a study in cynomolgus monkeys conducted during the early development of deferiprone, doses greater than 150 mg/kg caused deaths when given orally once daily for c. 20 days of a scheduled 3-month treatment period. We present results from a 12-month oral toxicity study of deferiprone in naive and iron-loaded cynomolgus monkeys, using twice daily dosing and compare them with findings in a similar study in rats. Cynomolgus monkeys (4–6/sex/group) and rats (20/sex/group), iron loaded by intraperitoneal injection of iron dextran, were given deferiprone as two equal daily oral doses totalling 0, 75, 150 and 200 (250 after 3 months in monkeys) mg/kg/day; naive monkeys were given 0 and 150 mg/kg/day for 12 months. Measurement of all standard parameters, including toxicokinetics, was included. No mortalities, no adverse clinical signs, and no effects on body weight gain, food intake, cardiovascular function or eye morphology, were observed in either iron-loaded or naive monkeys. Haematological and plasma chemistry parameters were largely unaffected by treatment with deferiprone; intermittent increases in serum activities of some hepatic enzymes were related to iron loading. Similarly, histopathological changes were limited to those associated with iron deposition in tissues. Plasma deferiprone concentrations achieved were significantly in excess of clinical exposures. Both naive and iron-loaded rats were less tolerant of long-term administration of deferiprone. Both divided daily dosing and iron loading may have contributed to the markedly better survival of monkeys in the 12-month study compared with the earlier investigation, and the results of this work confirm the value of the model in the evaluation of the safety of iron chelators.

The efficacy and safety of long-term administration of alpha-interferon and lamivudine in patients with chronic hepatitits B

2001 ◽  
Vol 120 (5) ◽  
pp. A572-A572
Author(s):  
F JABOLI ◽  
E RODA ◽  
C FABBRI ◽  
S MARCHETTO ◽  
F FERRARA ◽  
...  
Keyword(s):  
Alpha Interferon ◽  
Efficacy And Safety ◽  
Term Administration

STUDIES IN THE SUPPOSED GOITROGENOUS EFFECT OF TAP WATER IN HELSINKI

1960 ◽  
Vol XXXIII (IV) ◽  
pp. 630-636
Author(s):  
F.-E. Krusius ◽  
P. Peltola
Keyword(s):  
Tap Water ◽  
Physiological Saline ◽  
Normal Weight ◽  
The Body ◽  
Iodine Uptake ◽  
Redistilled Water ◽  
Detectable Difference ◽  
Term Administration ◽  
Long Term Experiment

ABSTRACT The study reported here was performed in order to examine the tap water of Helsinki for its alleged goitrogenous effect. In a short-term, 24-hour experiment with rats, kept on an iodine-poor diet, we noticed no inhibition of the 4-hour 131I uptake, as compared with that of animals receiving physiological saline instead of tap water. Two similar groups of rats receiving 1 and 2 mg of mercazole in redistilled water showed a distinct blockage of the 4-hour uptake, which proved the effect of this substance. In a long-term experiment of 5 weeks' duration there was no detectable difference in the body weight, thyroid weight and the 4-hour 131I uptake when the rats receiving tap water or distilled water to which 0.45 per cent of sodium chloride was added were compared with each other. Replacement of tap water by a 10 mg per cent solution of mercazole in redistilled water enlarged the thyroid to double its normal weight and increased the 131I uptake to approximately five times that of the controls. Thus our experiments failed to demonstrate any goitrogenous effect in the tap water of Helsinki. Changes similar to those produced by a long-term administration of mercazole, i. e. an enlargement of the thyroid and an increased thyroidal iodine uptake, have been shown to be due to milk collected from goitrous areas. The observations here reported confirm the importance of milk in the genesis of the goitre endemia of Helsinki. Attention is further called to the fact that a thyroidal enlargement combined with an increased thyroidal iodine uptake cannot always be taken as a sign of iodine deficiency because similar changes may be produced by the administration of goitrogens.

EFFECTIVENESS OF ANTIAGGREGANT THERAPY ON KIDNEY ACTIVITY IN THE PREDIALYSIS STAGE OF CHRONIC KIDNEY DISEASE

2020 ◽  
Vol 6 (1) ◽  
pp. 55-60
Author(s):  
Khabib Barnoev ◽  
◽  
Sherali Toshpulatov ◽  
Nozima Babajanova ◽  
Keyword(s):  
Chronic Kidney Disease ◽  
Renal Function ◽  
Kidney Disease ◽  
Comparative Study ◽  
Functional Status ◽  
Stage Ii ◽  
Term Administration ◽  
Antiaggregant Therapy

The article presents the results of a study to evaluate the effectiveness of antiaggregant therapy on the functional status of the kidneys in 115 patients with stage II and III chronic kidney disease on the basis of a comparative study of dipyridamole and allthrombosepin. Studies have shown that long-term administration of allthrombosepin to patients has led to improved renal function.

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