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Biomedical subjects

I Simonović

Publications and source records attributed to I Simonović.

At least 19 recordsLinked to original sources

Superiority of Mi-ADMS to DMSA as parenteral treatment for decreasing mercury (203Hg) body burden in rats.

The efficiency of meso-2,3-dimercaptosuccinic acid (DMSA) and the monoisoamyl ester of meso-2,3-dimercaptosuccinic acid (Mi-ADMS) in decreasing 203Hg retention was evaluated in rats in relation to age and time of treatment. The experiments were performed on six-week- and seven-day-old Wistar rats, which received 203Hg by intraperitoneal administration. The chelators DMSA or Mi-ADMS were also administered intraperitoneally, twice, on two consecutive days, in doses of 0.25 mmol/kg body weight as early (0.5 and 24 h) or delayed treatment (24 and 48 h, or 48 and 72 h) after 203Hg administration. The retention of 203Hg was determined in the carcass, liver, kidneys and brain six days after administration using gamma scintillation counters (double crystal, well type). In all experimental conditions, regardless of the animals' age and time of chelation therapy, Mi-ADMS was found to be superior to DMSA in reducing the body burden of 203Hg in whole body and organs. Mi-ADMS therefore seems to be a very promising chelator in the treatment of mercury poisoning.

Animals↗

Factors influencing the efficiency of chelation therapy.

The purpose of the present study was to obtain new data on the effect of age, route, dose and time of metal and chelating agent administration on the efficiency of chelation therapy. The experiments were performed on 1-2 and 6-week-old rats which received radioisotopes of metals--203Pb, 115 mCd, 203Hg and 141Ce intraperitoneally or orally. Chelating agents calcium ethylenediaminetetraacetate (CaEDTA), calcium and zinc diethylenetriaminepentaacetate (CaDTPA, ZnDTPA), 2,3-dimercapto-propane-sulfonate-1 (DMPS), dimercaptosuccinic acid (DMSA) and sodium N-(4-methoxybenzyl)-D-glucamine dithiocarbamate monohydrate (MeOBDCG) were administered twice by intraperitoneal or oral administration as early (immediately and 24 hr after metals) or delayed treatment (24 and 48 or 48 and 72 hr after metals). The animals were killed six days after metal administration and the retention was determined in the whole body, carcass and gut. After intraperitoneal administration of metals and chelating agents chelation therapy had much lower efficacy in younger than older animals. After ingestion of metals oral chelation therapy was more effective in younger than older animals. In suckling rats the treatment effectively reduced metal retention and this was mostly due to decrease in gut retention. This treatment in sucklings was also very effective in condition of late administration. In older rats early oral DMPS treatment after 203Hg ingestion is contraindicated since it increases significantly mercury retention while DMSA and ZnDTPA treatments reduced mercury retention. Delayed oral treatment with ZnDTPA and DMSA caused increased cadmium retention in older rats and decreased retention in sucklings. Opposite to results with CaDTPA, MeOBDCG was effective in reducing cadmium retention also when given as delayed treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Effect of imaging time on the values of the sacroiliac index.

Quantitative scintigraphy of the sacroiliac joints was performed in a group of normal subjects and a group of subjects with unilateral and bilateral sacroiliitis. The aim of the study was to determine whether the time intervals of imaging had any effect on the values of the sacroiliac index. Imaging was performed every 30 min up to 300 min and the indices were calculated at the time intervals mentioned. We found that the values of the sacroiliac index increased in the group of normal subjects until 150 min after the application of the radiopharmaceutical, and that in the group of subjects who had sacroiliitis they increased until 210 min. The results show that the time interval optimal to quantitative sacroiliac joint imaging is at least 3 1/2 h after administration of the radiopharmaceutical.

Adolescent↗

131I dose to the human fetal thyroid in the Zagreb district, Yugoslavia, from the Chernobyl accident.

The 131I activity was measured in 30 human fetal thyroids in Zagreb district after the Chernobyl accident. A model of radioiodine metabolism in the mother and human fetus which takes into account the age dependence of the uptake and retention of radioiodine in the fetal thyroid was developed. Having assessed that the total intake by the average mother was about 1330 Bq, a good correlation between calculated and measured fetal thyroid activities was found (r = 0.77, P less than 0.001). The fetal thyroid dose reached the maximum of 0.43 micro Gy/Bq intake at about the fifth month of gestation. It was concluded that the risk of having a child with a harmful trait due to 131I absorbed by the mother was negligible.

Accidents↗

Developmental pattern of the testicular androgen response to gonadotrophin stimulation in vitro and its modification by chronic hypoprolactinaemia.

Developing male rats were treated chronically with bromocriptine (BR, 3 mg/kg b.w. daily) to maintain severe hypoprolactinaemia throughout postnatal development. This treatment induced a precocious increase in Leydig cell numbers per testis and caused substantial, but age-dependent, modifications of the androgenic responsiveness of incubated hemi-testis preparations to stimulation with hCG. Most conspicuous were: (i) a decrease in sensitivity of the testis to hCG at the approach of adult age (due presumably to reduced responsiveness of the Leydig cells), and (ii) a precocious increase in the steroidogenic maximum of the testis at peripubertal age. This probably resulted from the precocious increase in Leydig cell numbers, which was able to mask the negative consequences of reduced androgenic capacity per Leydig cell. The precocious increase in number of Leydig cells induced by hypoprolactinaemia could have resulted from facilitation of the proliferative action of the high prepubertal LH levels on Leydig cell numbers. There were no clear-cut indications for an important effect of BR-induced changes in LH levels, or of a direct effect of BR on the testis.

Androgens↗

Rapid naloxone-induced alterations of androgen variables in the growing male rat.

Contrary to earlier views on the inability of naloxone to affect androgen variables by way of general circulation, systemically applied naloxone (2.5 mg/kg body weight, single i.p. or i.v. injection) has been shown to rapidly induce (within an hour) a significant fall (-35.7% on the average) of the concentration of serum androgen (testosterone and dihydrotestosterone; (T + DHT) in peripubertal rats (51-58 days old). Such a response to the opiate antagonist was absent, however, in low-androgen prepubertal animals (37-44 days old) and in those among peripubertal rats which still showed subcritical initial levels of androgen in circulation (less than 1.5 ng/ml; experiments with repeated blood sampling in catheterized animals). In peripubertal rats naloxone was also shown to induce a significant decrease (-36%) in basal in vitro androgen production by testes removed 15 or 30 min following the intraperitoneal administration of the opiate antagonist. Such an inhibitory effect on basal steroidogenesis has not been observed in control multiple-dose experiments in which incubated testes from naloxone-naive rats have been directly challenged with naloxone; on the contrary, enhancing direct effects were recorded, but only with the highest concentration of naloxone tested (10(-4) M). The possibility thus remains open that indirect inhibitory effects of injected naloxone may be operational in intact animals. Hypoprolactinemia, known to interfere in an age-dependent manner with the responsiveness of Leyding cells to luteinizing hormone (LH), may be of particular relevance.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

The effect of composite oral treatment for internal contamination with several radionuclides on 131I thyroid uptake in humans.

The efficiency of a composite oral treatment on 131I thyroid uptake was investigated in three adult volunteers. The treatment consisted of 10 g of calcium alginate, 3 g ferrihexacyanoferrate(II), 130 mg of potassium iodide and 5 g of Zn-DTPA. This mixture when administered 30 min before 131I almost completely blocked the 131I thyroid uptake. This indicates that simultaneous administration of other antidotal agents do not cancel or decrease the effect of potassium iodide on 131I thyroid uptake. The finding deserves attention since composite oral treatment is the recommended therapy in cases of accidental environmental exposure to several radionuclides.

Administration, Oral↗

131I uptake in human thyroid after antidote treatment for mixed fission products contamination.

The efficacy of a mixed antidote treatment in blocking 131I uptake in humans was investigated in two volunteers. Simultaneous oral administration of 10 g of calcium alginate, 3 g of ferrihexacyanoferrate (II) and 130 mg of potassium iodide 30 min before 131I administration caused an almost complete block of the 131I thyroid uptake in both subjects. This indicated that calcium alginate and ferrihexacyanoferrate (II) had no influence on the blocking effect of potassium iodide on 131I thyroid uptake. This finding is important because mixed antidote treatment is the recommended treatment in cases of accidental exposure to mixed fission products.

Adult↗

Efficiency of a composite treatment for mixed fission products in rats.

The effect of a composite antidotal treatment - consisting of a mixture of calcium alginate, ferrihexacyanoferrate(II) and potassium iodide - administered in diet and/or Na3(CaDTPA) administered intraperitoneally on the absorption and the removal of radioactive strontium, caesium, iodine and cerium was investigated in 7-week-old female rats. The animals were on respective treatments for 3 days. The retention of 141Ce, 85Sr, 137Cs and 131I was determined in the whole body, carcass, gut, liver, kidneys and respective critical organs (femur, muscle, thyroid) 6 days after their oral or intraperitoneal administration. In animals which received the antidotal mixture or Na3(CaDTPA) alone, the radionuclide retention was practically the same as in rats which were given the composite treatment [mixture + Na3(CaDTPA)]. This indicates that the efficiency of one treatment was not increased by the other. For 141Ce, Na3(CaDTPA) was an effective antidote, while 85Sr, 137Cs and 131I were reduced by the mixture. It is concluded that the composite treatment might be a quick treatment for choice for reducing mixed fission products retention, especially in cases when identification of exposure is difficult or impossible to make.

Alginates↗

Age and intestinal retention of mercury and cadmium in rats.

The site of cadmium and mercury retention in the intestine was determined in 6-day-old sucklings and 6-week-old weaned rats 6 days after oral administration of 115mCd and 203Hg. The ileum was found to be the main site of intestinal retention of both cations in sucklings but not in weaned rats. Other age- and element-specific differences in the site of metal retention in the intestine were also found. These differences indicate that even in neonates, metal absorption might be a more specific process than previously assumed.

Aging↗

Iodine in diet increases mercury absorption in rats.

Increasing the iodine content of rats diets caused an increase in the whole-body retention of 203Hg after oral, but not after intraperitoneal, administration. That iodine increases gastrointestinal absorption of inorganic mercury might be of interest in conditions of simultaneous environmental exposure to both elements, and therefore deserves further investigations.

Animals↗

Effects of bromocriptine-induced hypoprolactinaemia on the developmental pattern of androgen and LH levels in the male rat.

In immature male rats, receiving daily injections of bromocriptine (3 mg/kg bw), serum prolactin (Prl) remains low throughout development. In such hypoprolactinaemic males androgen variables are affected: a) the normally low pre-pubertal serum androgen (testosterone, dihydrotestosterone-T, DHT) is considerably increased, in correlation with a precocious development of the testicular Leydig cell population; b) the peri-pubertal rise of androgen is not prevented, but is is followed by significantly lower post-pubertal T, DHT levels, in correlation with moderately reduced Leydig cell counts and with strongly attenuated growth rates of sex accessory organs. Observed alterations of the post-natal androgen pattern cannot be related to LH changes since developmental LH values remained essentially unaltered. Results are in concordance with a marked age-dependent sensibility of androgen variables to a lack of Prl in the developing male.

Androgens↗